Tim, a non-Hodgkin lymphoma & prostate cancer survivor, father of two, and basketball coach, shares his journey from the shock of a cancer diagnosis to his recovery and newfound passion for cycling.
Prior to his non-Hodgkin lymphoma diagnosis, he wasn’t feeling well, was very tired, and had swollen lymph nodes.
His prostate cancer was discovered months after finishing treatment for non-Hodgkin lymphoma when his primary care doctor noticed his rising PSA levels. Given the different treatment options, he chose to have his prostate removed, despite initial reservations about the robotic surgery involved.
Dealing with cancer, he emphasizes the importance of a strong mindset and having a support system, drawing strength from his faith, support group, and friends. Facing the diagnosis alongside his mother’s battle with breast cancer, Tim hopes that his experience can inspire others.
Despite the challenges, Tim’s positive mindset and faith played a crucial role in his recovery, encouraging others to persevere through difficulties with the belief that tomorrow will be better.
Tim’s story is part of the “Our Voices, Our Power” series by The Patient Story. Discover more of the series by exploring Paul’s prostate cancer story.
Thank you to Janssen for its support of our patient education program! The Patient Story retains full editorial control over all content.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Name: Tim J.
Diagnosis:
Prostate cancer
Initial Symptom:
None; caught rising PSA levels
Treatment:
Surgery: prostatectomy
No matter how tough it is today, tomorrow is going to be better.
I’m a cancer survivor, a father of two awesome sons, and a basketball coach. I recently discovered a passion for cycling.
I grew up in North Carolina. I was the son of a Pentecostal minister. My father was also a farmer so I definitely know the meaning of hard work.
First Cancer Diagnosis
Initial Symptoms
I wasn’t feeling well and was very tired. My lymph nodes behind my ears, my armpits, and my groin area were swollen. I couldn’t sleep.
I finally decided to go to the doctor. My primary care doctor was pretty sure that I had cancer.
They did the first biopsy in the office. They cut behind my ear to remove some tissue. It wasn’t good enough so they had to do another biopsy where they sedated me and took more tissue. I had to wait about two weeks.
I received a phone call one morning. “We need to see you as soon as possible.” When I walked in, I had a feeling that the news wasn’t going to be positive. It was a very uneasy feeling not knowing how that visit would go, but I knew that it wasn’t good news.
There have been moments in the past when I was feeling the same way, but it didn’t linger. It disappeared. This time, the pain progressively got worse and very uncomfortable.
Getting the Lymphoma Diagnosis
My doctor started by saying, “I have good news and bad news. Which one would you like to hear first?” I asked him for the bad news first. He said, “You have cancer.” At that time, he didn’t know was lymphoma because the test results hadn’t come back yet.
Then I said, “Give me the good news.” He said, “The good news is this is the best cancer you can have.”
Once I found an oncologist, we did a spinal tap, which was very painful but a process that must be done to see if the cancer got into my bones. I was very relieved that it didn’t.
In a few days, I found out I had non-Hodgkin lymphoma.
Reaction to the Diagnosis
I didn’t know how to take that. Cancer is cancer. I was in shock, but had a sense of relief, in a way because now I knew the reason why I wasn’t feeling well. Now that we are here, we can start the process of what would be the next step for me.
I wanted to be proactive. If there’s something that I need to do, the more information I have will help me know how to deal with it to get to a place where this is no longer an issue. But I knew there was something wrong.
After receiving the initial diagnosis, I wasn’t worried about myself. I was worried about how to tell my family. How do you start that conversation?
I wasn’t worried about the future. My faith kicked in at that point. I wanted a plan of attack to get started with the process of healing.
The Impact of Faith
There’s no such thing as a perfect life. How boring would that be?
Growth comes from going through storms of life. My diagnosis was a chance to grow. It definitely gave me a more sense of awareness and appreciation for life that was much different than I had before.
Treatment
I went to treatment three times a week and had blood tests every week.
After my first treatment regimen, the cancer was still active in my lymph nodes so we started another treatment regimen. My doctor thought that would work best for me.
Side Effects of Treatment
I lost my hair. It affected me in a much different way.
Throughout treatment, I continued coaching and working. I continued being a part of my honor guard team, which was very important to me.
I maintained my lifestyle and activities as much as possible to help me not focus on my circumstances and what I was going through. Of course, there were days when I wasn’t feeling like this, but they weren’t as often as I thought they would be.
In Remission
I had my last cancer treatment in April, two days before my birthday. A few weeks later, I saw my doctor for a routine visit and he informed me I was in remission. He also told me that remission doesn’t mean that you’re necessarily cancer-free. It does mean that you will have flare-ups occasionally.
I never had that explained to me that way; that was a shock. But on days that I don’t feel that well — and I do have those days — I have something to relate it to.
Second Cancer Diagnosis
Initial Symptoms
In January 2020, I relocated from Long Beach, California, to Savannah, Georgia, for work. In the era of COVID, it was a very isolated time moving to a new city.
There, a primary care doctor noticed that my PSA counts were continually rising. He suggested I go to a urologist and have them run some tests. It was discovered that I had prostate cancer.
Getting the Prostate Cancer Diagnosis
It was a shock. I had been feeling very uncomfortable after riding a bike for numerous miles. This pain was different than being on a bike for 2 or 3 hours.
Reaction to the Diagnosis
It was hard to accept at first, especially knowing that a robot was going to be operating on you. I knew it wouldn’t be an easy recovery process.
I didn’t feel sorry for myself. If I could go through three years of treatment for lymphoma, I would be able to make it through this with no problem.
It’s a very painful recovery process, but I made it through and I knew I would. I just had to be patient. The healing process takes time. It doesn’t happen overnight.
Receiving that news for the second time, I was better prepared because I had already gone through that process of treatment for three years. But even then, I didn’t feel sorry for myself. My thought process was, Why not me? This will be part of my story to let someone else know that they would be okay. They can do it. You can come out of this storm stronger as well.
Breaking the News to Family & Friends
It was very difficult, but I knew I couldn’t keep it to myself because having a support team is very important.
As a father, we want to protect our children. But without sharing the news with them, we hurt them at the same time. It definitely brought us together and made our relationship much stronger.
My son was playing basketball in Finland at the time, but I knew that was a phone call I had to make. It was very difficult for me to share the news with him being in another country.
They were in shock. They felt sorry for me. It was hard for them to come and sit with me during treatment, but as I progressed and went into remission two times, they saw strength, confidence, and resilience.
Talk to your sons about your cancer experience and what they should be keeping an eye out for. I know more about my family history so I pass it on to them. It’s something that they should stay on top of and not be prideful about.
My circle of friends is very small, but a lot of my friends now are in the cycling community. I’m riding with a group I’ve never ridden before. They’re having a meeting and a doctor is going to be present. One of the things they’re going to be talking about is the stigma in the community of men and prostate cancer.
I share my story with them very briefly. My words are very short and to the point. I tell them, “I’m a cancer survivor and I’m blessed to ride with you guys today. It’s no joke. If you’re not feeling well, you should go get checked out. It may be something that’s not going to go away. It’s better to find out now. I’ve lost friends because they were too shy or too proud and didn’t want to tell anyone.”
Talk to your sons about your cancer experience and what they should be keeping an eye out for. I know more about my family history so I pass it on to them. It’s something that they should stay on top of and not be prideful about.
Sharing that news with my mother was very difficult because she was battling breast cancer in North Carolina at the same time.
I was diagnosed with cancer for a second time. My son was in Finland playing basketball. There was a lot going on, but I knew I had my faith to fall back on and I could see myself assuming my normal daily life.
Unfortunately, I couldn’t sit down for more than 5 minutes at a time. I was allowed to work from home, but it meant standing up as soon as I could. A friend was nice enough to drive with me to North Carolina to see my mother. Unfortunately, that was the last time that I saw her. She passed away the following week.
My mother’s very strong. Being strong, knowing that you’re going to be okay, and falling back on your faith came from her. She was more worried about how I was doing than what she was going through.
Dealing with a Cancer Diagnosis
Cancer is not something you can plan for. Cancer can affect you at any age. When it affects you personally, there’s a choice you have to make. How do you deal with it?
Having a strong mindset from the beginning can make a difference. From the day I received my diagnosis, I could see myself after the process and the healing process was over.
I didn’t focus on my circumstances at the moment because I knew this was something I would recover from. However, that would be a process that I would have to go through, but it was one that I wasn’t afraid of. I knew I would be okay.
Prostate Cancer Treatment Options
I was given three options. I could have my prostate frozen, undergo radiation treatment, or have my prostate removed. I asked my doctor what choice would he make if he were in my position. He said he would have it removed so I made the same choice.
After three years of immunotherapy treatment, I didn’t want radiation because of what it does to your body. For me, the best choice after getting advice from my doctor was to have my prostate removed and deal with the process of recovery and healing.
I had a chance to discuss my options with the surgeon as well as my primary care doctor. A team of doctors gave me what they thought the best options were and what the side effects would be.
Recovering from Surgery
It was difficult at times not being able to sit, not being able to sleep the way you wanted to, and being confined home a lot. Your whole approach to your body functions is a lot different.
It’s a very long, painful process, but I’m blessed it was found early because I could have had a much different diagnosis.
Follow-up Protocol
I see my oncologist every six months. There were blood clots in my lungs that were discovered during a routine check in August 2022 so I was placed on a blood thinner.
I continue to cycle. I didn’t let that stop me. After four months, they took me off blood thinners. We still don’t know the reason why the blood clots were there, but life goes on.
Importance of a Strong Support System
My high school basketball head coach had my initials along with our trainer who was also going through cancer treatment put on the jerseys for that season. They had us come up. To have a high school cheer for you made a big difference.
A good support group comes in handy. You can pick up the phone and say, “Hey, I’m not feeling well. I have this test coming up.” To have someone to reassure you that everything’s okay makes a big difference.
My faith was first and foremost. That was my go-to. I also had my support group and my friends from church.
It’s very important to have a first responder, someone you can go to when you receive bad news.
My circumstances don’t control who I am, but at the same time, I have a core support group that I can reach out to when I’m not feeling my best. They reassure me that I’m okay and I can reassure them that they’re okay.
Stigma of Prostate Cancer
I feel there’s a stigma. Part of the stigma could be not having the financial coverage that should be available to everyone. Pride is a factor.
Men are very proud. I’ve got this. Nothing’s wrong. I’m going to be okay. Even if I feel uncomfortable for a week, it’ll go away. If I tell my friends about this, they’re going to think less of me. my friends are going to laugh at me. They aren’t going to understand. My kids aren’t going to understand.
When your body is telling you that there’s something wrong, don’t ignore it.
I’ve had conversations with my sons and told them if they’re not feeling well, go to the doctor. It’s important to know your family history.
Unfortunately, I grew up not knowing my family history. My father was a Pentecostal minister and they didn’t believe in doctors. As a young man growing up and you don’t know your family history, it puts you in a high-risk category. The only time I went to a doctor when I was younger was for my physical for sports.
I believe everyone’s given a gift in life. When you’re not feeling well, your body tells you. It’s very important to listen to your body and go to a doctor rather than trying to diagnose yourself.
My story can be used to cheer someone else on. I became stronger, more generous, and more understanding of others. There’s nothing more powerful than when you’re going through treatment.
I’m blessed to sit here and tell my story and have that opportunity to bless someone else.
Words of Advice
I’m human. I allow myself to have those thoughts but not stay there. We have freedom of choice, especially with the way we think. I would welcome that thought but never let a negative thought control who I am because that’s not who I am.
Storms of life are going to happen. How you choose to navigate through them is up to you. I became stronger for my children.
Share the news with your family as soon as possible. You will have good days and bad days, but when you have a core group of people who love you and care about you, they will be there for you on those bad days.
Listen to your body. If you’re not feeling well, go get checked out. Don’t wait to have tests done. They’re vital because they’re very important to staying on top of your health.
Be strong for someone else who may be going through the same thing.
Cancer is part of my life story, but fortunately, I’m blessed to share this story with other men who may not want to get checked out. Even women ask me how I’m able to do what I do. First, my faith. Second, I didn’t let my circumstances control who I am.
Having a very strong mindset from the beginning is the key. See yourself not where you are now, but where you will be when you go into remission. Realizing that through that process there will be days when you’re not feeling your best. But remember, those days won’t last for long.
New Motivation
Cycling gave me an outlet during COVID. I could get out and ride in Savannah for 10, 12, 15, 20 miles to clear my head. It gave me a new sense of purpose and not let what was going on around me and the world affect me.
Cycling is a process. It starts with being mentally tough, just like going through treatment. I feel empowered. I’m doing something that I never thought I would be doing, but I’m blessed to do that.
Cycling has given me a second chance, another option to be active. It also allowed me to tell my story. I met an awesome young man who is going through treatment and he told me about The Patient Story and how he thought it would be an awesome opportunity for me to share my story.
I have a sense of gratitude that I can ride 50 miles at 25 miles an hour. I can push it to 30 miles an hour.
As a cancer survivor, I hope that what I’ve gone through can give someone else hope to hang in there. No matter how tough it is today, tomorrow is going to be better.
I’m blessed to tell my story. I didn’t know when that process started that a bike would be my saving grace. But it was and I could use that as part of my journey to help someone else.
Special thanks again to Janssen for its support of our independent patient education content. The Patient Story retains full editorial control.
Lena was diagnosed with stage 1 diffuse large B-cell lymphoma (DLBCL) and shares her journey from pre-diagnosis to life after cancer.
Initially, she had blood in her urine, which she thought meant a UTI. After being treated with antibiotics, her symptoms first alleviated and then worsened, which eventually included clots in the blood. Further tests revealed a bladder tumor. Despite having no typical signs of DLBCL, the diagnosis came unexpectedly after she had surgery to remove the bladder tumor.
Lena recounts the challenges of chemotherapy, including severe reactions to certain medications and the emotional toll of losing her hair. Following chemo, she underwent a month of radiation, which she found relatively easy compared to the previous treatment.
She highlights the various side effects faced during and after treatment, such as neuropathy, loss of taste, and early menopause. She also emphasizes the importance of managing emotional well-being, seeking support during and after cancer treatment, and staying strong throughout the cancer journey.
She shares her positive approach, acknowledging the support received from family, friends, and medical professionals. She encourages open communication with doctors, advises against excessive online research, and advocates for finding the right medical team and support groups.
In addition to Lena’s narrative, The Patient Story offers a diverse collection of diffuse large B-cell lymphoma (DLBCL) stories. These empowering stories provide real-life experiences, valuable insights, and perspectives on symptoms, diagnosis, and treatment options for cancer.
Name: Lena V.
Diagnosis:
Diffuse Large B-cell Lymphoma (DLBCL)
Staging:
1
Initial Symptom:
Blood in urine
Treatment:
Surgery
Chemotherapy: R-CHOP
Radiation
This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
I’m 53 years old. I’m a wife, a mother, and a grandmother. I enroll students for a university in Arizona. I live just outside of Phoenix in Mesa.
My husband has a motorcycle. We like to go motorcycle riding in the winter when it’s cooler because it’s so hot in the summer.
We have lots of kids around us and grandkids that we like to spend a lot of time with. We are a blended family of six children, ages 32 to 14. The 14-year-old lives with us. He’s our last one in high school.
We have learned to be very grateful and live our best life. Every day is a blessing.
Pre-diagnosis
Initial Symptoms
I had no symptoms that are typically involved with diffuse large B-cell lymphoma. I didn’t have any pain, fever, night sweats, or weight loss. I was told after the fact that it typically affects men who are over 65.
I thought I had a UTI. I had a little bit of blood in my urine. I went to urgent care and they did the routine test, gave me an antibiotic, and sent me home. That alleviated the blood in the urine for a few days then it came back heavier and with clots in it. That’s when we knew there was a problem.
It was completely out of the blue. I was healthy. We were newlyweds. We were about a year and a half into our marriage. We sold a house that we had as a rental and we were doing some work on the inside of it. We were celebrating my son’s birthday the next month.
I remember going to the bathroom at the restaurant three times. I thought I was getting a period. I wasn’t sure, but I had no pain. The next couple of days, it seemed like there was always blood and I thought I had a UTI or it was in my kidneys. The reason I went to urgent care was to make sure there was nothing else going on.
I took the antibiotic they gave me for a week and the blood had alleviated. There was no blood for about 3 or 4 days then it started to come back slowly and I thought, Maybe this infection is coming back. Maybe it’s farther into my kidneys than I thought. I still didn’t have any pain, fever, or any other symptoms but the blood.
There were clots in the blood so it was getting harder to urinate because the clots were blocking the way. I was trying to use the bathroom and it hurt. I couldn’t go at all because there was a blood clot blocking the way. I didn’t realize that at the time, but I figured with everything that had happened that was the issue.
I was crying and my husband said, “We’ve got to get you to somebody.”
Trying to Get a Urologist Appointment
The next day, I called a urologist and told them what my symptoms were. I had to call six of them because they were so busy. One of them was backed up for about six months and I thought, I can’t wait that long. That’s a long time.
I found an opening the next day, but it was with a nurse practitioner. I said, “I’ll take it. I will absolutely take it. That’s fine.” I saw her and gave a urine sample, but it looked like a cup of blood. She said, “Everything that we’ve tested looks very interesting so I’m going to send you over and we’re going to get a scan done.” That’s when I went, “This is not good.”
Getting Referred to a Cancer Center
I went over the same day to check in and I drove into the parking lot and it was Ironwood Cancer & Research Center. That’s when I thought, Oh boy, is this cancer? I didn’t know because she didn’t know and she didn’t tell me it was. She said, “We’re going to take a look at it because we don’t know what’s going on.”
The urologist was amazing. He took out most of the tumor. He couldn’t remove all of it because it was attached to the wall of my bladder.
Getting a CT Scan
I had the scan done on Valentine’s Day. On Monday, which was President’s Day, I got a phone call and they said, “We’ve looked over your scan. You have a tumor in your bladder.” It was about 5 cm, which is the size of a lime. They said, “We’re going to have to remove it immediately so we’re scheduling you for surgery on Thursday.” This went from zero to surgery.
Surgery to Remove Tumor
I had the surgery done and the urologist was amazing. He took out most of the tumor. He couldn’t remove all of it because it was attached to the wall of my bladder. He said if he removed it all, it would have perforated my bladder and that’s a whole different lifestyle for me so he opted to leave part of it there to protect my bladder.
Going in, they thought I might have bladder cancer and he said the tumor looked nothing like bladder cancer, which typically resembles a flower. We thought maybe it was a cyst. At that point, we thought, Wow, it’s not cancer! That’s great! We didn’t even think it could be a different kind of cancer.
After my surgery, the doctor spoke to my husband and my mom who had flown from Montana to help. He said, “We’re going to send this off for a biopsy.” I went home with a catheter for a week to help my bladder heal.
Had we not caught it when we did in February, I would not have made it to my birthday in September. It probably would have killed me before then.
Diagnosis
Getting the Official Diagnosis
The day I had my catheter removed, the doctor accidentally called my husband on his way home from work, thinking it was my number. He ended up telling my husband my diagnosis and my husband had to tell me, which I can’t imagine being in his shoes.
He came home and pulled me away from my mom to take me into the other room and said, “Dr. Matthews called me accidentally, but he told me what’s going on. You have diffuse large B-cell lymphoma.”
I was trying to be so optimistic. I said, “I have no idea what that means.” He said, “It’s a type of cancer in your blood and he’s very thankful that we caught it because now you can get treated for it. You’re going to do six rounds of chemo and a month of radiation possibly.”
Thankfully, it was caught because Dr. Matthews told me this type is very aggressive. Had we not caught it when we did in February, I would not have made it to my birthday in September. It probably would have killed me before then.
I knew nothing about staging. I was stage 1, which means it didn’t spread to any other areas of my body so that was why they did the bone marrow biopsy. They wanted to make sure it wasn’t in my bones.
The scans were to make sure it wasn’t in any of my organs that were around my bladder. My bladder pretty much contained it all, luckily, because it could have spread to my liver, to my stomach, and all of those organs right there. My bladder held it in and that’s what saved me.
Reaction to the Diagnosis
My mom is a breast cancer survivor. She was on hormone replacement therapy, which is what caused her to have breast cancer. She had a mastectomy done. She’s a fighter. She’s tough, she’s fierce, and she’s feisty. She’s a little Thai woman and she’s hilarious. I take after her quite a lot in that area.
I sat there in shock after my husband Dave told me and thought, Wow, really? Are you sure? I got upset a little bit because my dad wasn’t there. We shared the news with my mom and she had this look on her face. She stood up, slapped my arm, and said, “You’ll be fine,” and walked out of the room. I said, “She’s right,” and that was the attitude I had the whole time. This isn’t over. I’m just starting.
‘I have a lot of life to live. Can we get started ASAP?’
Treatment
Discussing the Treatment Plan
After we had determined my steps, I was referred to an oncologist at Ironwood Cancer & Research Center, which was a mile and a half from our house. I met with Dr. Monique Chang. I had my mom and my husband with me.
The minute I went in there, I said, “Look, I have a lot of life to live. Can we get started ASAP?” She said, “Oooh, you’re a spitfire.” And I said, “I am. This is not going to get me. We’re going to do this.” And she said, “Absolutely.”
We set up the appointment for chemo, but I had to have an echocardiogram, a port placed, and a bone marrow biopsy. They wanted to make sure that it wasn’t in my bones. Those were the next steps before my first treatment.
Chemotherapy
I did R-CHOP, which is a very common treatment for DLBCL, but I also have the Neulasta device on my arm. The device itself didn’t hurt. It helps rebuild your bone marrow so it’s very painful when you’re healing from that.
The injection is the day after chemo. It injects you for about 30 minutes and it’s painful the next couple of days out. It was probably about a week after that that you ache. Your bones ache because it’s regenerating all those white cells for you.
I did chemo every three weeks from March to July 2nd. My very last treatment was on my husband’s birthday.
Radiation
After chemo, I did a month of radiation. The doctor wanted to make sure they got everything. It was one treatment daily for the whole month of August 2018.
Radiation was a piece of cake for me because I didn’t feel anything. They made a pillow that fit my body in the area where they were scanning it and I would just lay there. It was under 30 seconds every day and I was out of there. The wait in the waiting room was longer than the radiation itself.
After chemo, I had a stutter so it took me a while to be able to talk again to where I could piece a sentence together.
Side Effects of Cancer Treatment
R-CHOP was difficult. On my very first chemo day, we went at 7:30 in the morning and they told us it was roughly 5 to 6 hours. For us, it was almost 11 because I reacted to vincristine, which they call the Red Devil.
It was brutal. The first time I had it, I turned red and felt like my insides were made of lava. I felt like I was melting. It was that bad of a reaction. They slowed down the drip for that and that helped so I never had a reaction again.
In between each medication, they gave me Benadryl so I was completely groggy by the end of the day. Honestly, I’m not sure how my husband got me out of the car and into the house. I remember that being a very, very long day.
I had to take prednisone as well, which is not my friend. I know that it’s very helpful for a lot of people and it’s part of the regimen for this particular type of cancer.
I was taking five doses of prednisone a day for five days each time I had the treatment. I gained a lot of weight because of it. Normally, cancer patients lose weight because of chemo and being sick and nauseous. That may be the case, but the prednisone started packing on the pounds.
I had bad neuropathy. I still suffer from neuropathy. Five years later, I still have some issues. Not as bad as they were, obviously, but with every chemo session, I would get a headache right at the base of my skull and nothing would make it go away. It would go all the way down my arm.
By the end of chemo, I couldn’t tell the difference between hot and cold. My fingers and toes were numb. My hands and feet were a different color. They were grayish. I heard it’s a typical change. There was another patient there who she said all her toenails and fingernails fell off. They turned black and fell off from chemo.
Many different things can happen to you. I tried acupuncture to alleviate some of the pain, but it did not work for me. They tried to put me on gabapentin and other antidepressants, but the side effects from those were so bad that I didn’t want to do them.
I never regained a period so I got pushed into early menopause and had heavy, heavy hot flashes. I would have them for minutes at a time for probably about six months, midway through chemo until the end of that year.
I still have hot flashes, but they’ve slowed down. I didn’t take any hormone replacement therapy after my mom went through what she did. I said, “Absolutely not. I’m not going to do it. I’ll naturally let my body figure it out.”
After chemo, I had a stutter so it took me a while to be able to talk again to where I could piece a sentence together. I would try to talk and it would not come out. That took me close to a year to feel like I could speak normally again.
My very last chemo treatment was almost as bad as the first one. I was disappointed because it’s your very last one and you’re thinking, Oh, I’m done. This is great! I’m finished! It kicked my butt and I was down for about a week. Typically, after each treatment, I would be out of it. It was never the day after. It was the day after that for 2 or 3 days when I didn’t feel right at all.
I lost my sense of taste for almost two years. It’s still off. I love coffee, but it does not taste the same as it did at the beginning of 2018. It’s not the same.
I didn’t have any side effects from radiation. They told me, “You could have blood in your urine.” I freaked out when I heard that, thinking, I don’t ever want to see blood in my urine ever again. They said I could be fatigued. They said I could have burn marks. I had none of those so I was very lucky.
I’m not going to sit here and feel sorry for myself because it’s hair. It’s going to grow back. My mom’s came back after her treatments. It will come back.
Hair Loss Due to Chemo
My son was eight when I was diagnosed. We honestly weren’t going to tell him. I said, “We can hide it. I’ll be okay.” I told the nurse, “I’m not going to lose my hair.” And she said, “Oh no, sweetie, you’re going to lose your hair. You don’t have a chance to keep any of it.” I thought, I’ll be the one that does. It’s okay. I’ll be the one, trying to psych myself up.
I woke up one day and our white bedding had a big pile of hair. I started brushing it and the sink was full of hair. That was after my first treatment.
I cried for about an hour and a half, sitting there, pulling it, and combing it. I could feel where I had little patches and thought, I’m not going to sit here and feel sorry for myself because it’s hair. It’s going to grow back. My mom’s came back after her treatments. It will come back.
That night, my husband shaved my head. Not gonna lie, it was hard. It was hard for him. He didn’t want to do it. I said, “I need you to. I can’t do it by myself.” At the time, our son came in and said, “You shave my head, too,” so we all shaved our heads together.
It’s tough. It does grow back. My hair grew back weirdly. Initially, it grew back white and stubbly. That all fell out and then it grew back to salt and pepper, which was appropriate for my age, but it was curly like I had a perm. That lasted about a year. Then as it grew out, it returned better than it was. It’s thicker and healthier than it was before.
Managing the Side Effects
The neuropathy is much better. I use CBD oil; that was the only thing that relieved the pain. I take CBD gummies to help me sleep.
I’ve been suffering from neuropathy for about a year and a half. I was trying Tylenol, ibuprofen, and Aleve, and nothing was working. I thought, This is something I’m going to have to deal with. I’m alive. If this is the worst of it, I accept it. I’m still alive.
One of my friends and I were standing and having a conversation and she said, “Have you ever tried CBD?” I said, “No, I never really gave it a thought.” She said, “You should try these.” I thought no because in my mind, you’re going to smoke weed and I didn’t want all those weird side effects either. I thought, No, it was never my thing. I’m not that girl. I don’t want to do that.
She said, “There’s no weed in it. Let’s try it.” She had a little tincture bottle in her purse and she put two drops under my tongue. Within an hour and a half, the pain was completely gone and it never came back.
It’s not going to work for everybody. I got lucky that she suggested it because I probably would have never done it on my own.
Once you reach the five-year mark with this particular type of cancer, you are considered cured.
Monitoring with Scans
I was pretty good about keeping a journal. I’m very organized. I kept every piece of information because I still have chemo brain. There are things that I’ve forgotten that people remind me of and I can’t remember.
I had the CT scans and PET scans often when I was going through treatment. I had one at the beginning, one at the midpoint, one right before my final treatment to make sure it was going to be my final treatment, and one after my final treatment.
I’ve had to have a cystoscopy where they go up into your bladder with a camera. My urologist at the time was wonderful. He has since retired, but I never felt any pain and he was amazing. He was a good source of positivity.
I don’t have to have a cystoscopy or scans anymore. If I start to feel anything off, they told me to come back and they’ll check me out completely.
At the end of chemotherapy, they said that everything looked clear. November 6th was my final cystoscopy after chemo. That was when Dr. Matthews said there’s no evidence of disease so that is what I count as my anniversary date.
Dr. Chang told me that once you reach the five-year mark with this particular type of cancer, you are considered cured. I was thankful that she removed my port when she did because many patients have to keep a port in for at least a year or two after treatment. She was confident enough to let me get mine removed.
I said, “I can sleep on my stomach again. I don’t have this object protruding out of my chest and I don’t have people staring at me.” I don’t care if you stare at me now. This is a badge of honor, honestly. It was a good feeling to hear that there was nothing left.
When I saw Dr. Chang not long ago, she said, “You did it.” I said, “You helped me do it because there’s no way I could have done it alone.” She’s amazing. She’s in the Phoenix top 100 physicians and she’s incredible.
Even on my worst, worst, worst day when I was miserable and in bed crying because I was in so much pain, I knew there was light at the end of the tunnel.
Managing Scanxiety
I know it’s not realistic for all people, but if you can, have somebody go with you. My husband typically would go with me and wait with me. I would go in there with a positive attitude.
I know it’s hard. It is hard. Even on my worst, worst, worst day when I was miserable and in bed crying because I was in so much pain, I knew there was light at the end of the tunnel. I had to keep going because if I gave up, what good would I be to my kids, my grandkids, and my family who were watching me struggle and were helpless?
You’re the one in charge of your emotions every day. You have to get a hold of that and stay positive. Because if you let go of that and you sink into this hole, it’s really hard to get out of it.
I wanted my normal life back and it was never going to be like that again.
Life After Cancer
I had a hard time after treatment because I went into a bad depression, which made no sense. I’ve been used to this routine and being taken care of by these specific people. Then when you’re done and you don’t have that routine anymore, even your friends fall by the wayside. They check in once in a while. This is pretty common from all the people I’ve talked to so it’s not their fault.
When you think about somebody going through cancer and then they’re done with their treatment and they’re in remission, a lot of times people think you’re okay. We’re not okay.
I went through a lot of mental struggles. I had to go see an integrative oncologist. She was like a counselor. She tried to get me back to my new normal, which I was sick of hearing. I wanted my normal life back and it was never going to be like that again.
If you have a doctor that is not listening to you, it’s not the right doctor for you.
Shared Treatment Decision Making
I had a terrible family doctor who had the worst bedside manner and who wasn’t sympathetic. I’ll never go to another doctor who doesn’t understand and listen to me first of all.
A lot of times, people need a second opinion if they’re not comfortable with their doctor. With the surgeon whom he referred me to, I researched on her before I even saw her. When I talked to her, I thought, If I’m not comfortable when I talk to her, I don’t care what kind of accolades she has, I will find another doctor, because I’m very much one that will speak out and advocate for myself.
She listened to me and my needs. When I told her I was going through the pain with neuropathy, she was the one who sent me to the integrative oncologist who then asked, “Lena, what do you need most? I can put you on antidepressants. I can put you on this.” I said, “I don’t want to take medicine. I’ll do lion’s mane to rebuild my brain. I’ll do whatever it takes. I don’t want to take any more pills.”
She worked with me. She suggested acupuncture. She suggested lots of other things that were great. If you have a doctor that is not listening to you, it’s not the right doctor for you.
If you’re going through something, you have to reach out and let someone know. There is a ton of support.
Words of Advice
I shared a lot of information on social media not because I wanted attention for what I was going through. I wanted to share my feelings and be honest with people. I had people messaging me, saying, “Hey, my mom just got diagnosed.” “My brother got leukemia.” I’m able to use what little voice I have to try to help those people get through it.
I’m a big advocate for speaking up for yourself. If you’re going through something, you have to reach out and let someone know. There is a ton of support. I found that out after the fact because I lost friends with cancer through my journey. You have survivor guilt plus depression plus not going to treatment anymore. I miss my nurses who were fantastic in my recovery.
You’re in a whole new cycle of life that you’re trying to navigate and you still have it in the back of your head. Every doctor’s appointment, every time I go for a scan, every time I have blood work done, I think, Something’s going to go sideways.
Talk to somebody, even if it’s a stranger. LLS has all kinds of resources and support. They were huge in helping me find support. My oncologist had a list. They had support groups at Ironwood Cancer & Research Center. They were supportive. They had mental health checks.
I wish people would reach out. It’s important. If you’re feeling any type of way, do something about it because sitting there is not going to help. You’ve got to talk to somebody.
When you get diagnosed, do not Google anything. Don’t have family members do it. Don’t have friends do it. I was told that immediately and I listened. Had I done it, that would have probably put me down a rabbit hole of despair and giving up. Everyone’s journey is completely, completely different so stay on track.
Listen to your doctors. If they’re not listening to you, find a new doctor
Find support groups. There are tons of them out there. That’s how I found The Patient Story. I was posting about Light The Night when Instagram suggested The Patient Story.
There is hope. Don’t give up. Stay fighting. Stay strong.
Cindy was diagnosed with stage 4 diffuse large B-cell lymphoma (DLBCL) in April 2021 and concurrently battled COVID.
About a month before getting diagnosed, the palms and soles of her feet started getting itchy. Later on, her skin started turning yellow and she was feeling sluggish. Since she never got sick, she didn’t think anything of it until her eyes turned yellow as well.
She took herself to the ER and there found out that her bile duct was completely blocked, in which they performed surgery to put a stent in.
Not long after, she tested positive for COVID and had double pneumonia and super pneumonia. To give her lungs a break, she had to be intubated, not realizing the severity of her condition.
Her oncologist was so relieved upon seeing her in his office since not all patients have the same outcome as her. Once she started treatment, the tumors started shrinking immediately.
She shares her journey going from being extremely healthy to getting diagnosed with cancer and getting COVID, how she had to relearn breathing, swallowing, walking, and talking, and her spiritual journey while she was in the ICU.
In addition to Cindy’s narrative, The Patient Story offers a diverse collection of diffuse large B-cell lymphoma (DLBCL) stories. These empowering stories provide real-life experiences, valuable insights, and perspectives on symptoms, diagnosis, and treatment options for cancer.
This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
I am retired so I’m no longer working. I have a couple of kids and six grandkids.
I have a couple of dogs that keep me as companions. I’m in remission now from the diffuse large B-cell cancer.
Pre-diagnosis
Initial Symptoms
I was diagnosed in April 2021. The skin on my palms and soles of my feet started to get itchy maybe a month before. I thought it was dry skin because it was still winter. I ignored it because I was in extremely good health. I never get sick.
My skin started turning yellow a couple of weeks later. I made an appointment with my primary care physician. I was a little sluggish and tired, but I wasn’t sure why. I thought I was working too hard so I ignored those. I told myself, “If my eyes turn yellow, I’ll go in.”
They turned yellow so I took myself to the ER, called my kids, and let them know. My daughter came to join me. They did blood tests and CAT scans. They came up with this horrible diagnosis that I was going to die from some rare type of cancer. They didn’t even know what it was.
I didn’t have time to process. I didn’t realize I was that sick.
They called a GI specialist who came in and did an endoscopy. That’s when they determined I needed to do surgery immediately because my bile duct was completely blocked.
They asked for a urine sample. The urine was red so it wouldn’t have been much longer and I would have been dead in the next couple of days.
Diagnosis
Reaction to the Diagnosis
I didn’t know anybody in my family who got diagnosed with what I exactly had. There was one tumor around the bile duct and one in the liver hiding.
It was surreal. I’d been extremely healthy. I didn’t get colds, flu, or anything. It was a shock.
I didn’t have time to process. I didn’t realize I was that sick. I went to the ER, got the surgery, got blood work, saw the oncologist, and started treatment the following week.
I didn’t know what to expect. I didn’t even know what this cancer was. I couldn’t sleep so I watched TV a lot at night. I saw an infomercial about the type of cancers that Roundup was causing and they said, “Call one of our lawyers.” They took my case like nothing.
It’s been an interesting journey getting that sick. Honestly, even when I got out of the hospital, I never really thought I was that sick. It wasn’t until maybe six months later that it sunk in. Even when I had to learn how to walk, talk, and all that, I thought it was normal, but it’s not.
Those were challenges that I had to go through, but I stayed positive. I didn’t question anything and did what I was told. The way I looked at it, I’ll be okay by Christmas and be able to be with my family. That was my goal and that’s what I cared about. That’s what got me through everything.
I didn’t know what to expect. I didn’t even know what this cancer was.
Biliary Stent Placement
After they put the bile stent in, I started to get my color back.
Appointment with Oncologist
They scheduled me for an oncology appointment. When I saw the oncologist, he was very real. He said, “I can cure this hopefully in 6 to 8 treatments.”
He asked if I had any questions. My daughter, poor thing, was crying her eyes out. I felt bad for her. What I heard was that I can be cured. What she heard was a death sentence because she heard chemo.
I asked if I was going to lose my hair. He said yes. She cried more. I said, “It’s just hair. It grows back. It’s not a big deal. Who cares?”
My other question that she couldn’t believe I asked was, “Can I still drink beer?” I like beer. He said, “Yeah, two a week.” He knows once you get on chemo, who wants a drink? You’re sicker than a dog.
They did blood work the week before I saw the oncologist and he explained what type of cancer it was and what type of chemo they were going to do. They have you watch videos, give you pamphlets, get the port put in, and start getting you hooked up.
My daughter asked, “If she doesn’t do chemo, how long will she last?” He said, “She’ll be dead by July.” It was that aggressive and I didn’t know. I was always against chemo, but when you’re in that position, you change your mind real quick. If that’s what’s going to save my life, so be it.
Testing Positive for COVID
I tested positive for COVID. My lungs were acting up, but they still sent me home only to come back three days later and be admitted for a month. I was intubated in between that time because the COVID was so bad.
If I never had chemo, I could have been okay with COVID. I never got sick. This is new to me so I didn’t know I was that sick.
I was rolling with the punches. I slept all the time. That was all I could do. I had no energy.
My lung capacity was going way down and I was on oxygen, but it didn’t concern me. I thought that I’d snap out of it sooner or later. Even when they said they needed to do a transfusion, it didn’t concern me.
Getting Intubated
On my daughter’s 40th birthday, they woke me up and said, “We need to intubate you. We need to give your lungs a break.” As far as I was concerned, it had to sign the document and that’s all it has to be.
I could barely talk. My daughter planned a trip to Mexico and I kept trying to tell her, “Go on your trip. There is nothing you can do for me.” She was so emotional that I didn’t think she could hear what I was saying.
The next thing I know, I’m intubated. I remember waking up and being tied because I tried to pull it out, but I don’t remember that.
I remember waking up one time and biting it nervously. It’s an ordeal to be on a breathing tube. Nobody wipes your saliva so it goes down the back of your neck. Your nose runs and nobody cleans it. Your lips are severely chapped.
They do bathe you. Thank God for the port because that’s how they fed me.
My lung capacity was going way down and I was on oxygen, but it didn’t concern me. I thought that I’d snap out of it sooner or later.
Spiritual Journey
The things that I remember were crazy. During one of those times, I believed I was going to die because I saw my body float past the stars to the universe. I could see around the world.
I saw people from Saudi Arabia praying. I saw my friends and relatives who were Catholics praying with candles and my other cousins who were in two different congregations. My kids’ dad, who was Native American, was doing a ceremony in a teepee. All of these people were praying.
Seeing those woke me up to the things that I took for granted like breathing, walking, talking, and swallowing, which I all had to relearn.
When I felt myself slipping, I prayed. All that came back to me. Am I religious? No, I’m more spiritual. But I was asking the universe, God, anybody, “Just let me live. I’ll figure it out from there.”
I begged for my life that night.I woke up and the sun was out. I was so grateful. I wasn’t out of the woods.
When I could talk, the first thing I asked my daughter was, “Did your dad do a ceremony for me?” She said, “How did you know?” I said, “Because I saw it.” I asked my two cousins, “Were you guys praying for me? Each one of your congregations?” They said yes.
The one that stumped me was Saudi Arabia. I don’t know anybody there. I told my father about it and he said his wife’s daughter married Saudi Arabian. They live there and they told them so their whole congregation was praying. That’s what I saw.
When I felt myself slipping, I prayed. All that came back to me.
Getting Off the Ventilator
They tried to get me off the ventilator. I couldn’t talk, but they put me on a Zoom video call with my daughter. They put the phone on my chest and all I could hear was, “You breathe the same air that we breathe, Mom. They’re going to take you out tomorrow. Take deep breaths. You’re going to be fine.”
The next day, they said, “We’re going to take you off. Honestly, the worst thing is the stickers on your face that hold the breathing tube.” I didn’t feel the breathing tube coming out. They were too busy sticking their fingers in my mouth and checking that I didn’t crack my teeth.
The nurses loved my bald head. They’d come by and rub it all the time.
Recovering from COVID
It’s been an interesting journey being shut in because COVID was really bad. I had no immune system. I didn’t dare go to a store. I didn’t go anywhere out of the house except to the doctor’s visits or blood work. I was very cautious. I never want to be that sick again.
I had a double pneumonia and a super pneumonia from COVID so my lungs are scarred. Can I handle another pneumonia? I don’t know and I don’t want to find out.
My mother was very sick when I was a child. She had heart disease so she was intubated several times. We saw that and she came out of it every single time. To me, when he said they were going to intubate me, it didn’t scare me. I thought I’d be fine.”
My kids couldn’t understand that. You hear people dying from COVID, but in my mind, I’m going to come out of it. I’m going to be okay somehow.
Treatment
Getting back to the oncologist, I was determined to get off the walker and walk into the oncologist’s office with no cane and I did do that. He was so incredibly happy to see me. He kept saying, “So good to see you, my friend. So good to see you. I watch your chart every day hoping you weren’t going to die. When do you want to start chemo?” I looked at my daughter, “Why is he asking me that?” She said, “Do you not have anybody like my mom?” He said, “No, they all died.”
I want to get on with treatment as soon as possible because I want to get on with my life. His being concerned that the cancer was so aggressive scared me a little. I figured I had already gone through the worst. Plus I was trying to get my strength back.
I’m grateful to my children for being here, taking care of me, cooking my food, and helping me. You lose so much strength and muscle. Taking a shower is horrendous. It’s an energy sucker. I had to learn all these things a little at a time.
Side Effects of Treatment
Five days after treatment, I got neutropenia. I ended up in the hospital for a week.
I only had one chemo after coming out of the hospital so it did make me tired but not more tired than what I had already been through.
I never got nauseated, which was a good thing. I did get neuropathy so now I have chronic neuropathy. I have chronic lower back pain. I don’t know what to contribute that to other than being in the hospital for so long and staying in the same positions plus the shortage of nurses to turn you when you’re in ICU.
The last chemo kicked my butt. That left me weak for weeks.
I want to get on with treatment as soon as possible because I want to get on with my life. His being concerned that the cancer was so aggressive scared me a little.
Follow-up Scans
The tumors were starting to shrink very fast. They were almost gone on the first treatment, but he wanted to do two more to make sure.
Right now, their only concern is a small lesion on my liver. They don’t know what it is. It’s staying steady, but it’s still there.
Some of my blood work for the liver is still high and we don’t know why. The liver could be damaged, probably from the chemo. I don’t know how long it takes to recover. The last scan I had still shows the lesion.
He may want to do a liver biopsy if it shows up again in six months. It might be scar tissue.
Life After Cancer
I hadn’t been out in so long that I didn’t even know what’s what anymore. There’s so much new development.
I went to play darts once and in the back of my mind, I got freaked out that I was around a lot of germs, but my counts were pretty good so I felt okay. It’s summertime and the doors are open.
In the fall, I’m not going anywhere. I do believe that my immune system is better. My granddaughter comes over and she’s been sick twice but I didn’t so I must be doing okay.
I don’t want COVID again. That put the fear of God in me. I don’t even know if I can handle the flu. It’s an interesting journey going from being extremely healthy to this crazy cancer because that never ran in my family.
They said I had to relearn to swallow; that’s part of having the breathing tube. I thought they were kidding me, but they didn’t lie because I tried to swallow Jell-O and it freaked me out. Even today, I have problems swallowing.
I have to chew my food in tiny little bites because I’ll choke. They can stretch it if they want to, but I don’t want to do that because I’ve had so many surgeries and procedures.
Staying Positive
Being positive is the key to anything, regardless of what you do in life. I never asked why me because why not? Why not me?
Words of Advice
Stay positive. It’s okay to get angry, but don’t dwell on it.
Try not to feel sorry for yourself because it’s not going to do any good. You’re going to give cancer the advantage. Go in with the attitude that you’re going to kick its butt. They give you all the tools to kick its butt.
Know that you’re not alone. It’s unfortunate, but you’ll get through it. There’s no reason not to.
I had a rare cancer. They told me I was going to die, but I thought to myself, No, I’m not because you don’t know me.I’m not going to die. I don’t care what kind of cancer you say I have. It’s not going to happen.
Be positive and know yourself. I’m pretty stubborn so that helps.
I’m alive and kicking. My grandkids and my dogs are happy. I get so excited to see a full moon or the leaves change. I appreciate life.
Patients, care partners, and a panel of CLL experts including Dr. William Wierda, MD, Ph.D. from MD Anderson, Dr. Nicole Lamanna, MD from the Columbia University Medical Center, Dr. Adam Kittai, MD from the Ohio State University, and Jackie Broadway-Duren, PhD, DNP, APRN, FNP-BC from MD Anderson gather to share the latest in CLL research, clinical trials, treatments, and comprehensive care strategies.
Guided by the insights of patient advocate moderator Jeff Folloder, the discussion will bridge the gap between medical expertise and patient perspectives, creating a truly comprehensive dialogue.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Navigating Clinical Trials for Lung Cancer: A Patient’s Guide
Is a Clinical Trial Right for Me?
Edited by: Katrina Villareal
Understand the different lung cancer types and the significance of biomarker testing through this recorded conversation. Learn about the evolution of biomarker testing inclusivity for all patients. Know more about KRAS and EGFR biomarkers, available treatments, and ongoing clinical trials.
This program was produced in close collaboration with our partner KRAS Kickers. We thank them for their time, expertise, and passion.
Get expert insights on current and promising clinical trials. Find out the importance of proactive patient engagement in finding suitable clinical trial opportunities.
This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Stephanie Chuang, The Patient Story: Hi, everyone! I’m Stephanie Chuang, founder of The Patient Story and a cancer survivor myself.
The topic of clinical trials can be pretty daunting. Some may know a lot and some may not even know what a clinical trial is. We’ll try our very best to cover as much ground as possible with our incredible panelists.
We’re collaborating with KRAS Kickers, a grassroots nonprofit led by patient advocate leader Terri Conneran, who will lead the discussion devoted to KRAS: knowledge + research + advocacy = survivorship. Their focus is on any KRAS oncogene or cancer type with the mission of connecting people to the latest research resources and community.
We’re co-hosting with them here at The Patient Story. I founded the patient and care partner organization after my own cancer experience, going through hundreds of hours of chemo, and feeling really alone.
Our mission is to humanize cancer so you know that you are not alone. We also invest in educational programs to help empower you and your loved one in your own care. We cover cancers across the board, including lung cancer, with a focus on biomarkers and clinical trials.
We want to give special thanks to Amgen, Mirati, Genentech, and AstraZeneca for supporting our educational program. We want to stress that The Patient Story and KRAS Kickers retain full editorial control of this entire program. This program is not meant to be a substitute for medical advice. We want you to walk away knowing more, but please consult with your own medical team before making decisions.
Terri Conneran
Stephanie: Many of you may have already seen or heard our patient advocate moderator, Terri Conneran, who shared her story on our platform. I’m very lucky to call her a friend now.
Terri, a lot of us know how passionate you are as an advocate. You’re out there making sure people know how to be empowered in their care. Can you share more about your personal story and what led you here?
Terri Conneran: It’s such a blessing to be anywhere after you get diagnosed with lung cancer. I was diagnosed with non-small cell lung cancer, went through chemo and surgery, and had no evidence of disease.
I connected with other lung cancer groups and heard about biomarkers. Not getting the information I needed or wanted from my doctor, I eventually, after about two years, got a second opinion. The second opinion doctors told me I had KRAS.
I wanted to connect with other people so that we can all learn what this means and how we can make it better to live with KRAS cancers. We need to take KRAS and turn it into knowledge + research + advocacy = survivorship. We’re all here together to kick cancer’s KRAS so I’m delighted to be here. This is all about the hope that we’ve learned over the years.
Dr. Estelamari Rodriguez
Terri: We have Dr. Estelamari Rodriguez, a hematologist-oncologist at Sylvester Comprehensive Cancer Center at the University of Miami Health System. She specializes in early detection and treatment of lung cancer.
Dr. Estelamari Rodriguez: Thank you for the invitation. Delighted to be here.
Dr. Jason Porter
Terri: We also have Dr. Jason Porter, a hematologist-oncologist at the West Cancer Center Research Institute in Memphis, Tennessee. He’s the director of the Lung Cancer Disease Research Group and specializes in treating patients with molecularly-altered lung cancers and lung cancers with no actionable driver mutations.
Dr. Jason Porter: I’m super excited. Estela, it’s so good to see you again and I look forward to the discussion.
Different types of lung cancer
Terri: We’ve got a lot of ground to cover. Dr. Porter, what are the different types of lung cancer?
Dr. Porter: When somebody is new in my clinic, they want to know, “Do I have the really bad one or the one that’s not so bad?” Most people have heard that small cell lung cancer (SCLC) is more aggressive so that’s in the back of people’s minds. Basically, what it means is when we look under the microscope, how do the individual cancer cells look? Are they big or small?
Non-small cell (NSCLC) is the same thing as saying large cell or cells that aren’t as small under the microscope. We divide that into three categories: non-squamous, squamous, and large cell neuroendocrine carcinoma. Outside of those three, there are other rare histologies that we don’t see quite as often, but those are the more common ones.
Adenocarcinoma is the most common type of lung cancer and the most common non-small cell lung cancer then it’s squamous cell carcinoma. Large cell neuroendocrine is a different type of tumor.
When we look at the patient’s body, the trachea breaks off to the left and right lungs and squamous cells line the the epithelium; that’s the type of tissue that we see in the upper airways. Adenocarcinomas happen more peripherally in the lung fields. Small cells can pretty much happen anywhere.
Biomarkers are genes that drive cancer. We have been successful at identifying at least 10 of those.
Dr. Estelamari Rodriguez
Different lung cancer biomarkers
Terri: Dr. Rodriguez, what are the different biomarkers?
Dr. Rodriguez: When I started my training, we only knew about lung cancer as non-small cell and small cell. Now we really need to dig deeper into the genes that caused the cancer because today, we have 10 biomarker-driven treatments for specific types of cancers.
We know that a lot of these genes, mutations, and oncogenic drivers first described adenocarcinoma, but there are mutations in any type of cancer.
If you have a diagnosis of advanced lung cancer or even earlier stage lung cancer, it is important not only that you get a biopsy so that you understand the histology and how it looks under the microscope, but that you get that test about the genes that caused cancer.
Biomarkers are genes that drive cancer. We have been successful at identifying at least 10 of those, although a lot of them have been seen in adenocarcinoma.
Initially, they were in never smokers. We see them on people who have smoked a long time and who stopped smoking a long time ago so it really has nothing to do with smoking history. It has nothing to do with gender. It just has to do with the cancer.
It’s part of the information that’s critical to get at the beginning of the treatment so that you can pick the best treatment for the patient. A patient that gets started without that information may not be started on the right treatment. It’s important to do that test. It’s usually ordered in the tumor specimen or through a blood test called liquid biopsy.
Tissue biopsy vs. liquid biopsy
Terri: Is there a difference in what comes back from the liquid biopsy compared to a tissue biopsy?
Dr. Rodriguez: The gold standard of where we think we are most likely to find a source of the genes is going to be the tumor. But many times when you do a biopsy, you get part of the tumor that is very necrotic or dead tissue so the actual DNA inside that tumor is not good enough to get all the information that you need. You learn more from the blood.
The opposite can also happen. You can have a blood test that’s completely negative in terms of actionable mutations, but there’s a lot in the tumor specimen.
A lot of centers, mine included, try to do both tests because they can be complementary and specific. You can identify some mutations through the blood, especially RNA fusions where two genes come together.
With the blood test, we can do that in the office and get results in 7 to 10 days. Technology has allowed us to treat patients faster with the right treatment that we didn’t have available 10 years ago.
We’ve now discovered that we need to do biomarker testing in all lung cancers.
Dr. Estelamari Rodriguez
Most common types of lung cancer biomarkers
Terri: What are the most common types of biomarkers in lung cancer, Dr. Porter?
Dr. Porter: A long time ago, we found EGFR as a biomarker and then we have also the KRAS mutations. We actually found KRAS a long time ago and couldn’t target it for such a long time. It can serve as a biomarker that we can use to target for treatment and also a prognostic biomarker that gives us some information about how a tumor may behave.
We have both prognostic and diagnostic biomarkers outside of KRAS as well. We have PD1 and PD-L1, which are proteins that we can study to give us an idea about how our immune checkpoint therapies may work when we treat non-small cell lung cancer.
We also have BRAF, ALK, ROS1, and all these different proteins that may be driving the cancer or giving us information on how different cancers may respond to treatment.
We used to associate these biomarkers with non-smoking and now we have drivers that are actually associated with smoking.
Testing biomarkers is becoming very important for all patients regardless of their smoking history. BRAF is one of those biomarkers that we can see present in smokers as well as KRAS. MET exon 14 is another biomarker that’s also an actionable biomarker that we can target in therapy that may be associated with smoking.
We’ve now discovered that we need to do biomarker testing in all lung cancers.
Terri: Dr. Rodriguez, with the biomarkers, are you either one or the other?
Dr. Rodriguez: The world has become more complex as technology has allowed us to really dig in. It’s an alphabet of different mutations that are in each of these genes.
For example, with EGFR, the more common mutations are deletion 19 or exon 21 changes. But when you look at that whole protein, there are a lot of insertions and atypical mutations that we used to ignore because we didn’t identify them very commonly and we didn’t think that they mattered. But they do matter.
We have drugs developed, for example, for EGFR 20 insertion, which is something that was there all along and unrecognized. Those patients were not responding to the traditional treatments for EGFR because they had a different configuration of that protein so they needed a different type of drug to work.
The same thing with KRAS. There are a lot of KRAS mutations and it can be a whole alphabet of different KRAS mutations. KRAS G12C, which is a bigger proportion of those KRAS mutations, has two newly approved targeted therapies that we can offer.
We also see patients who have other types of cancers in other parts of the body who share these KRAS mutations and they may be of a different variety.
Because they’re all different, we have to invest in research to really define the best treatment for each of these parts of the mutation that the patient is encountering.
Testing biomarkers is becoming very important for all patients regardless of their smoking history.
Dr. Jason Porter
Latest clinical trial updates
Terri: We just came out of the big annual World Conference on Lung Cancer. Can you tell us some of the excitement that happened around KRAS or EGFR?
Dr. Rodriguez: Two things are happening. We’re getting more data from patients who have been treated for a long time in whatever option we had, like osimertinib, which is the first drug used for EGFR. We’re learning that people progressed. The next question is: how can we treat those resistant clones earlier?
One of the exciting data that came out was FLAURA2, a trial that used the same backbone of osimertinib, which is the targeted therapy that we use for most patients, and added chemotherapy. The question was: would patients do better if they had proper targeted therapy along with chemo? Will they be able to decrease the burden of disease and be managed better to prevent resistant clones in the future? That’s one of the theories.
I was happily surprised that it made a big difference. I always used to think that osimertinib works very well. You get a lot of responses. Then when it stops working, you can try chemo. However, I didn’t expect that patients would have almost nine months of improvement in disease. They were less likely to relapse if they were getting chemotherapy upfront.
With that same concept of making the treatment upfront more aggressive, there were other antibody-drug conjugates that were presented. We’re going to see a lot of exciting data with these new drugs that bind our receptors and inject chemotherapy into cells.
For EGFR, we saw a trial called HERTHENA that used patritumab, which is an antibody to HER3, which is another antibody similar to EGFR. It basically would inject chemotherapy into those cells that have become resistant. We saw data for that and there’ll be trials adding that antibody-drug conjugate to the first-line therapy.
We also saw the MARIPOSA trial, which is a drug approved for EGFR 20 insertion, trying to use that drug, which is an antibody-type drug, upfront with an EGFR inhibitor called lazertinib.
There’s a lot of excitement about combining drugs, not sitting back and waiting for things to happen, but trying to be more proactive. The data that was more mature was the FLAURA2 trial in EGFR.
Dr. Porter: KRAS, as I talked about earlier, is a very interesting biomarker because we’ve known about it for such a long time. One of the clinical trials in KRAS is the KRYSTAL-1 clinical trial. We have two drugs that are approved right now by the FDA for second-line use for KRAS G12C: sotorasib and adagrasib.
The KRYSTAL-1 clinical trial is a phase 1/2 clinical trial of patients with different tumor types that had KRAS G12C mutations and the non-small cell lung cancer cohort was included. We have data that continues to mature and we see response rates of around 35% in the non-small cell lung cancer cohort. These were patients with both smoking and non-smoking histories, mostly male patients.
As the data continues to mature, particularly in non-small cell lung cancer, it’s now been FDA-approved for use in the second line after patients progressed on an immune therapy-based treatment, so an immune therapy plus or minus chemotherapy.
Very interesting to see that, as Dr. Rodriguez alluded to with the FLAURA2 trial where we’re adding chemotherapy to targeted therapies, what the tolerability is going to look like and whether it is really going to cause benefit.
In KRAS G12C targeting in clinical trials, we have further study with adagrasib, which is looking to add chemotherapy to adagrasib with an immune checkpoint inhibitor.
It’s becoming a much more robust combination of therapies in the more advanced setting for KRAS G12C patients, where we’re familiar with the fact that KRAS G12C patients are more likely to be smokers so they’re probably having other co-mutations that may additionally be driving the tumor outside of KRAS G12C. This is where it becomes particularly interesting for me to see the addition of chemotherapy to the KRAS G12C inhibitor so that we are covering clones or parts of the cancer that are not actually being driven by the KRAS G12C mutation.
It will hopefully increase not only the outcomes for those patients, but also the response rates will hopefully be higher as we see with the EGFR inhibitor plus chemotherapy, and then the duration of response and survival for those patients.
Starting out with sotorasib and adagrasib now approved in the second line and then adding chemo and immune therapy to those drugs in more advanced settings upfront to hopefully improve outcomes, durations of response, and survival for those patients.
Terri: Essentially, it’s not like I only have one biomarker and that’s it. There’s a little bit more to it. There may be a biomarker that comes on down further or not as a result of treatments or what have you, but that makes a difference. Am I tracking with you?
Dr. Porter: Absolutely. It makes a huge difference. In the case of EGFR, as Dr. Rodriguez talked about, it’s more likely to be that one single biomarker that we need to focus on, maximize response, and benefit from targeting that pathway. But when it comes to KRAS, we know that there can be so many other drivers along with it.
Essentially, when I think about it, I think about if this patient were a smoker or if they had environmental exposures, they wouldn’t have one single driver. They may have other carcinogenic consequences from being exposed to cancer-causing agents like what we have in smoking or the environment like radon so more than one gene may be affected as opposed to these single gene-driven tumors like EGFR, ALK, and ROS1.
Dr. Rodriguez: The other thing that has become clear to me is that patients need to empower themselves with this information. There have been many cases in which I have seen second opinions or patients whom I have gotten to know where the information was there, but it wasn’t acknowledged.
They had a test earlier on in their disease and it was ignored because it wasn’t what the doctor was doing at the time. Either the patient went to surgery and they had a KRAS G12C mutation that wasn’t recognized or the patient had chemotherapy-immunotherapy and then that was not acknowledged and the patient missed an opportunity to get treatment earlier that we know can work.
Another part of this is understanding that science moves and there are new options and new combinations, but that you can’t make any decisions until you have the information in front of you.
We really need to be very strategic about what the treatments are. If you don’t have all this information going into it upfront, you can’t be strategic at all.
Terri S.
Terri: It is an exciting time. I’d love to drill down a little bit deeper into some of the clinical trials and what you guys are hearing and seeing.
Dr. Porter: For me, particularly with KRAS, the excitement got a little bit curtailed with the toxicity that we see sometimes when we add G12C inhibitors with immune checkpoint inhibitors. We may see a little bit more immune-mediated side effects like hepatitis, pancreatitis, and type 1 diabetes development.
The tolerability with the combinations was a little bit unnerving initially, but I think we felt the same way about immune checkpoint inhibitors when we first started using those, even in monotherapy. Imagine the experience with that first pneumonitis and the first dermatitis. I had a patient the other day who had some mucosal issues from immune checkpoint inhibition alone.
When we first encountered these, it was very unsettling. But now we feel so much more comfortable with these side effects. It’s really, really exciting to see the combinations of KRAS inhibitors with chemo, plus or minus immune therapy.
Right now, the unlikelihood of KRAS inhibitors being used in front-line monotherapy, to see those, explore the toxicity, and figure out how to use them in combination, modify doses, and do all of these things is very exciting. I assume, like we see with EGFR, that it’s going to improve outcomes when we’re able to bring them in combinations.
Any combination is very exciting. G13 is exciting to me, too. Again, I’ve only seen two in clinical practice and the first one was really a surprise to me. As we develop these pan-RAS inhibitors, again, more excitement for me.
Dr. Rodriguez: It was also seen in EGFR, but this whole message of treating patients earlier with chemo and targeted therapy really got my attention. In our practice, we have seen patients who have this mutation but have to wait for second line. We have to go through chemotherapy and immunotherapy and some of them get very sick. It’s very sad to me that they never got to see that targeted therapy.
In the trial that combined carboplatin-based chemotherapy with adagrasib, they saw responses of over 60%. They were able to bring up the responses that you wouldn’t see with chemotherapy.
Patients sometimes get a good chance to decrease the burden of disease. We know that some patients with KRAS mutations have a lot of burden of disease. It’s very aggressive. They have a lot of symptoms so if we’re able to help them with all our drugs upfront and we can find a way to deal with the toxicity, we’ll be able to help more patients.
Dr. Porter: Earlier, they’re more likely to tolerate a more robust regimen. It’s also exciting to get to do that a little bit earlier. We suppress the subclones that are being driven by the driver that we’re targeting.
When we aren’t able to use chemo and/or immune therapy upfront, those other clones that grow through are resistant to our therapy and may even be more resistant to chemotherapy later so we see lower response rates.
Where we have these drivers in the second line, it’s really sad to see those patients come to that point and be clinically unable to tolerate whatever the therapy is.
I had a patient with a G12C mutation who wasn’t a candidate for a clinical trial in the front line. When we got to the second line, his effusion was refractory, even loculated, and not amenable to easy drainage. He was definitely not a candidate for VATS (video-assisted thoracoscopic surgery) where we go in and clean that out so trying to get him onto the G12C inhibitor wasn’t possible. He couldn’t tolerate it.
He spent most of that time hospitalized and eventually went into hospice. When I first met him, he was walking into the clinic and still robust. Being able to target at that time would have really been nice for him.
Terri: We really need to be very strategic about what the treatments are. If you don’t have all this information going into it upfront, you can’t be strategic at all.
We want to forget the actual stigma but remember that stigma is a problem.
Dr. Jason Porter
Smokers & non-smokers
Terri: You mentioned that the EGFR group of patients is equal to the amount of KRAS G12C patients and yet they’ve had a whole lot more studies and a lot more drugs that have been going on.
We’re not there yet when it comes to other KRAS subtypes, let alone some of the others as well. You both brought up smoking. Is it that important where it got here from or is that one of those things that keeps getting reported out?
Dr. Porter: For me, it’s not important where we got here from, but what we have to remember is stigma. We want to forget the actual stigma but remember that stigma is a problem.
The reason I always bring up smoking is because I was sitting in a room with a very, very smart oncologist who told me, “This patient was a smoker so they’re less likely to have an oncogene driver.” I said, “Twenty years ago or 30 years ago, that would have been true.”
I like to use smokers, next-generation sequencing (NGS), and studies in the same sentence so that people start to make the association that you can definitely have a driver that’s actionable even with a history of smoking. You’re more likely to find BRAF, MET exon 14, and even KRAS with FDA-approved therapies in smokers.
Where it becomes relevant for a never smoker is we know they’re less likely to respond to immune therapy by itself. But for smokers, I like to keep saying that and putting NGS testing in the same sentence so people stop having this association that the oncogene driver patient is a young female, Asian, never smoker. That’s what we learned in medical school. We need to really change that narrative.
I don’t want it to seem like I’m harping on smokers. I’m harping on the fact that smokers can have drivers and that we have to study everybody. We have to.
Terri: Thank you for clarifying that because that’s exactly what I was hoping you would say. We definitely need to test and it’s important for what’s next.
We have two fantastic patients who went through clinical trials.
I highly recommend a clinical trial to anybody, but do your homework. Have an exit strategy in the event something happens or a side effect you cannot tolerate.
Mike S.
Mike’s lung cancer story
Mike S.: I have stage 4 lung cancer. I was diagnosed in 2016 and like most people, I was stunned, particularly since I was a non-smoker.
It’s been an uphill roller coaster ride, depending on what kind of medications I’m on, the side effects of those medications, or the availability of certain alternative treatments that I’ve been on for the last couple of years, including a clinical trial drug.
My initial diagnosis put me on the standard of care treatment and that lasted about 27 months. The efficacy rate was about 24 to 26 months.
In discussion with my oncologist and also with what treatments were available, I was presented with TAGRISSO, an FDA-approved drug, or I could go on a clinical trial.
Our thinking here was that if I went on a clinical trial drug that was supposed to work as well or better, then I could perhaps extend my life. They’re proposing that this clinical trial drug had an efficacy drug of two years versus an FDA-approved drug that had an efficacy rate of about three years. This particular drug was thought to be better than the FDA-approved drug.
I’m going to get scanned more frequently. I’m going to get a report card of my tumors. There’s a lot more testing, monitoring, and scanning that takes place because you’re on a clinical trial.
The additional monitoring was what prompted me to say yes to the clinical trial. I may have the benefit of getting additional months added to my life with the efficacy rate of a potential clinical trial drug working for a period of time.
Before I started the clinical trial, I met one of the nurses who was going to be assigned to me. She was great and explained the whole process. She also helped facilitate the scans, progress reports, meetings, and discussions.
I was one of the earlier ones to get in, but there weren’t a lot of people in the clinical trial. There was no drug name. I believe it was in phase 2 when I got involved.
Initially, I did really well. I had a reduction in tumor size. I was just astonished. I was getting monthly progress reports showing tumors shrinking so I was flabbergasted.
I made the right decision because the benefit of this is I got on a clinical trial that’s working. Even if it fails at some point, I’ve got a reduction in tumors. I’ve got an extension of life.
That lasted for about 10 months then the worst happened. I had a brain scan and it showed five brain mets. I reached out to several people in the lung cancer community who had similar situations but not from the use of a clinical trial drug.
Because they had brain mets, they switched to Tagrisso, which I had put off moving to because I wanted to try the clinical trial drug. Tagrisso was supposed to ward off any type of brain mets but also eliminate them if you had them.
I knew exactly what was going to happen if the clinical trial drug failed, which was to go on Tagrisso, in discussion not only with my oncologist previously but also with about 5 or 6 different lung cancer patients I knew.
I was pretty calm about this even though the placement of some of these brain mets was not good. I had one of my brain stem, which essentially made it inoperable.
When I went in, I saw the oncologist, the oncologist nurse, the nurse navigator, the social worker, and the nurse assigned to the trial. I thought this couldn’t be good because I don’t usually meet with a parade of people like this.
The discussion centered on some of the results and the five brain mets. I said, “What we’re going to do is move to Tagrisso, correct? When you tell me it’s inoperable, you can’t do anything. You can’t do radiation, right? I’m out of the trial. The intent is that this drug is going to eliminate these brain mets.” He said, “That’s correct. That’s our hope.” I said, “Okay, well, then that’s what we’re going to do.”
They were all looking at me like, “Wow, does this guy have nerves of steel or something or is he crazy?” I wasn’t reacting in the way they thought I was going to react. I was informed at the start of the trial what may happen. When I got negative results, I did the research, too, before I met with my oncology team.
After we met, everybody left the room and then a moment later, the nurse came in, gave me a big hug, and said, “Are you okay?” I said, “Yeah, I am. I know it’s what I was in for when I signed up for this. You are working to save my life and we’ve got a plan. I’m fine as long as we have a plan.”
What I don’t like is when something happens in the roller coaster journey of having lung cancer and you don’t have an established plan and you’re waiting for something. That’s when it gets a little bit more nerve-wracking.
There’s a lot of paperwork associated with the clinical trial because there’s the acknowledgment of the risks associated with going on a drug that you don’t know what it’s going to do to you. There’s an assignment of a lot of pages to read through and sign.
The nurse associated with the clinical trial did a very good job of explaining the risks associated with being on this drug. I didn’t have any problems with understanding the risks.
Prior to getting on the clinical trial drug, you had to do tests. I got off the prior drug for maybe a week or so before I started the trial to make sure I didn’t have any prior drugs in my system.
There are some attestations that you didn’t use the drug or any other drugs prior to starting the clinical trial. The attestations are pretty straightforward. They ask a lot of other questions.
For anybody who’s considering a clinical trial, do your homework not only at the front end but also at the back end. It’s not just about getting on the clinical trial drug. At some point, you’re going to get off the clinical trial drug. Generally, there’s an exit strategy.
I got out early because I developed brain mets. How the trial ended or not is confidential information. I had some conversations with my oncologist and the nurse associated with the study because they had to provide information to the clinical trial provider.
I highly recommend a clinical trial to anybody, but do your homework. Have an exit strategy in the event something happens or a side effect you cannot tolerate. You have an entry plan and an exit plan. Make sure you’re covering your bases with all those questions before you get on the drug and then be prepared for what may happen.
I had an extension of life for 10 months, but had I not gone on it, I would have gone on some other drug that had a different efficacy rate. I would wholeheartedly do it again in the availability of a clinical trial drug that meets my particular criteria.
It’s more important to get the right treatment than it is to get a treatment quickly. Ask as many questions as you can and don’t be afraid.
Joann J.
Joann’s lung cancer story
Joann J.: I was diagnosed in November 2021 with stage 4 non-small cell lung cancer KRAS G12V. I had several standard-of-care treatments, all of which resulted in progression. Luckily, I got on a clinical trial in February 2023. It was a targeted therapy and it was a daily pill, which was wonderful. No more infusions.
I had a great quality of life for six months with very minimal side effects. I was able to go back to work. I was in a really good place.
Unfortunately, my last scan showed progression and new growth, which is unusual for a targeted therapy. I have an upcoming biopsy on the liver, which is where the new growth is, and based on the results, we can figure out how to move forward.
My biomarker is KRAS G12V. We’re doing this liver biopsy to make sure that it’s the same cancer. I think the next step is another clinical trial, probably immunotherapy.
Through KRAS Kickers and Terri, it’s definitely something that I researched and looked into. The first time this particular clinical trial was mentioned to me was through my oncologist in New York. I was put on a waiting list.
I traveled to Dana-Farber in Boston and to MD Anderson in Houston to hopefully get on the trial sooner. Interestingly, Dana-Farber and MD Anderson would not allow me because I had a history of pneumonitis.
MD Anderson was going to put me on a different trial. I was all set to get an Airbnb and move to Texas for six months when, all of a sudden, they had a spot for me in New York for the RMC-6236 trial.
I definitely feel like my knowledge of the clinical trials and my aggressiveness in the whole process certainly helped me.
My only fear was whether or not I was going to get a drug or a placebo. From what I gathered, they don’t give placebos to cancer patients. It’s just cruel. Once I understood that, I was and still am very willing to go on any trial. It’s the future of cancer treatment so I have no problem.
I had a good experience and I know other people have not. When I went to MD Anderson, my insurance company paid for my airline ticket plus my husband’s. Things like that are very difficult. The financial toll is significant. In that respect, I feel very lucky. But I also feel like KRAS Kickers has definitely given me knowledge and, with that knowledge, strength.
For someone who may be considering a clinical trial, I would say go for it. Ask as many questions as you could possibly think of. A second opinion is always a good idea. It’s never a bad idea.
In fact, even if they don’t give you a different direction, the peace of mind you get is invaluable, knowing that the direction you’re going in now is the right way to go.
The first thing I learned in the cancer community is it’s more important to get the right treatment than it is to get a treatment quickly. Ask as many questions as you can and don’t be afraid.
Terri: Those are some powerful stories. These are real people who are doing these clinical trials. Pretty amazing.
Dr. Porter: It really is. To hear Mike’s excitement about the clinical trials and to hear how he thought about what the possibilities were as it was being presented to him, it’s really exciting. He really captured some of the things that our patients ask us when we bring up clinical trials and what they can expect.
Dr. Rodriguez: We don’t hear enough from people who have a good experience in a clinical trial. We have a lot of patients who think that they’re going to be experimented on and that they’re going to be getting a placebo.
I work in an experimental therapeutic clinic where everybody gets a drug. We’re not giving placebo drugs for phase 1 trials or phase 2 trials. They’re all about testing a drug.
We don’t know how well those drugs would work, but one of the things that has really changed in oncology is that we’re getting results faster and drugs faster for patients. Sometimes not as fast as you will need them, but much faster than they used to be.
Biomarker testing has allowed us to do better trials because now we can find the right patients who are more likely to respond to some of these treatment options. In the past, we will have a new drug and it will be given to everyone with or without chemo. The responses were obviously very low because you were not looking for patients who were more likely to benefit.
As a provider in one single location with limited resources, if I open the network and use everything out there, I exponentially increase the chance that my patient’s going to find something that’s tolerable and may be very effective for them.
Dr. Jason Porter
Importance of getting a second opinion
Dr. Rodriguez: I would encourage patients to think of second opinions as a good thing, not a bad thing. I have patients who come to me and say, “I’m sorry, I’m going to go speak to so-and-so.” I say, “I am delighted that you’re going to speak to someone else.”
We’re all friends. If you have a doctor that gets upset about this, it’s kind of odd. If I were going through this, I would want to learn from other people and get a different perspective. Maybe another doctor can see something that was missed. It is good to do that. You’re not going to hurt your doctor’s feelings and they’re not going to stop treating you.
Dr. Porter: Coming back from the World Conference on Lung Cancer in Singapore, I had a patient who was progressing. He said two letters to me, “MD,” and I was already typing an email to one of my colleagues at MD Anderson, saying, “Hey, my patient’s progressed and I don’t have a trial that’s right for him. Would you look at it?”
He’s going to see my colleague and it’s not about me or my feelings. I love my patient and I want him to be okay. I want to make sure he gets access to whatever is out there that may benefit him.
As Dr. Rodriguez said, if we get upset, it’s probably something odd about us. There’s really no reason to get upset. It takes a village and as a provider in one single location with limited resources, if I open the network and use everything out there, I exponentially increase the chance that my patient’s going to find something that’s tolerable and may be very effective for them.
Clinical trials sometimes give you the best therapy before it’s even available for general use.
Dr. Jason Porter
Clinical trials are NOT a last-ditch effort
Terri: It really is different than I thought it was because I’m not a doctor. I didn’t know anything about this. The surprise was that you don’t do clinical trials as a last-ditch effort. I had no idea there was an actual order to it, you qualify for it, and it matters a lot what your biomarkers are.
Dr. Porter: We don’t want to take it as a last-ditch effort because when we get ready to go on clinical trials, we have to control for as many variables as possible. Are the kidneys functioning okay? If something happens on the trial and the kidneys aren’t functioning well, it could be a complication of kidney dysfunction and then the drug gets associated with that unfortunate outcome. We have to control those things.
Earlier in a disease like lung cancer, you’re less likely to have some of those other disease issues that may exclude you from the clinical trials. Doing it earlier is better.
I came into my clinical practice around the time that immune therapy was starting to come into second-line FDA approval. I thought about the people who went on immune checkpoint inhibitor clinical trials, the ones who are still responding from 2013/2014. There are still some survivors. For those patients who went on early, the clinical trials sometimes give you the best therapy before it’s even available for general use.
Our guideline compendium says that the best therapy for a patient with lung cancer or with any cancer is in a clinical trial. If you end up getting in early, you have long-term benefits. Definitely not a last-ditch effort and sometimes access to the most effective thing available.
Identify the biomarkers early so you can get on the right track.
Dr. Estelamari Rodriguez
New immunotherapy trials
Terri: We had a question that was asked about new immunotherapy trials. Will previous trial patients be able to participate?
Dr. Rodriguez: That’s the beauty of earlier phase trials. The patients didn’t fail; the treatment didn’t work. You want to find a different way to treat them.
A lot of the trials that we do after immunotherapy is a new immunotherapy that is in a different way, a vaccine trial, or a different mechanism to try to wake up the immune system because, in a way, most tumors can possibly be treated with immunotherapy. They become what we call hot tumors that are more likely to activate the immune system. Some tumors lose that capacity. You have an innate resistance that is not a tumor that is very hot in that end and you can do something to it.
We have tried different things, like radiation followed by immunotherapy. There are a lot of exciting vaccine trials that are trying to push that immune response.
What we have seen success of is the memory of the T cells in a longer way, infiltrating T lymphocytes, which are white cells of your own body that get activated against the tumor and then given back to you to do a more directed immune therapy. Those are treatments that immunotherapy can possibly help patients with many different biomarkers.
Biomarker-driven research and treatment is very exciting because sometimes you get very deep and long responses.
Another exciting development is in the ROS1 and NTRK space. We had a new drug, repotrectinib. When we understand how you can bind these receptors and do better, then the next drug can have an even higher response. Some of these drugs have responses of 70% with intracranial responses that are over 40%. That means that we get better at the next generation of the drug.
That’s what I hope for KRAS G12C. We already have seen adagrasib and sotorasib have intracranial activity that is real.
I had a patient who I was getting ready for our next-generation KRAS inhibitor and I thought she was progressing. I did all the studies to get her ready for the trial. The one she was on was working very well. She had a response in the brain and the pleural disease she had went away. Identify the biomarkers early so you can get on the right track.
Terri: What a great problem to have that she was responding so well that she didn’t have to join the clinical trial.
Dr. Porter: Right, that’s exciting.
Patients can get a copy of their own biomarker testing. A lot of times, the results will list out the clinical trials that are relevant to that particular biomarker.
Dr. Jason Porter
Looking for clinical trials
Dr. Rodriguez: Patients who are most likely to go into trials are patients who have been on trials before. We have a lot of patients who had a good experience and that opens a whole new door of options for them. I would encourage people to look.
Fortunately, everything’s consolidated in ClinicalTrials.gov, a website where you can put in your mutation and your state, and get a readout of trials that are open. All of those trials have an email of an investigator and a nurse coordinator.
I do that for my patients. I say, “We’re going to write an email and you’re going to find out if this trial is open.” Sometimes there’s a trial right next door that you hadn’t even known about. You just have to do the work.
Dr. Porter: There is a lot of work.
If you are patient and your doctor is not really considering or giving you the option to discuss clinical trials, you may need to consider reaching out on your own, maybe get in touch with Terri or us, and see about what options may be there.
An amazing resource for finding a clinical trial is your doctor and that’s where you need to start. But obviously, you can’t wait in case that’s not presented as an option for you.
If a patient has access to their biomarker analysis or if they know they have any particular mutation, you may just search that mutation + clinical trials on the Internet and see what comes up. You may even type in your city to see what comes up in your city.
Patients can get a copy of their own biomarker testing. A lot of times, the results will list out the clinical trials that are relevant to that particular biomarker and even give you a listing of where those trials are.
We assume patients don’t want the information from the actual report of their next-generation sequencing but as we educate and get advocates out there, letting patients know how important biomarker testing is, they can find often a list of the relevant clinical trials for their biomarker right there on the report and that can guide them in their initial searches for clinical trials for their biomarker.
Dr. Rodriguez: We can forget that crowdsourcing for clinical trials is really one of the most effective ways. I have patients who have found trials because they were part of a patient support group. Someone in another state was in a trial and that opened up an opportunity to really look at a trial that was in the same state.
I had a patient who came from Jacksonville, which is pretty far from us, but she found the trial through the patient support group. You can reach out. People who have gone through other trials already have made connections and that can be very helpful.
Dr. Porter: A lot of patients want to know the purpose of a trial and if there are any risks associated with being in a trial. It’s a little counterintuitive, but if you think about it, you’re monitored so closely. Any risks are much more likely to be discovered while you’re on a clinical trial.
If there’s going to be any trouble with your kidneys or your liver while you’re on the clinical trial, which could happen with chemotherapy that’s already approved anyway, you’re going to be getting labs more frequently. You’re going to be coming in to see the nurse a little bit more frequently and possibly even phone calls from the clinical trial coordinators. You’re monitored a little bit more closely so I feel like it diminishes the risks that may be associated with the clinical trial.
Crowdsourcing for clinical trials is really one of the most effective ways. I have patients who have found trials because they were part of a patient support group.
Dr. Estelamari Rodriguez
Different stages of a clinical trial
Dr. Porter: As we get to the different stages or phases of the clinical trial, we have more experience with that particular drug so there’s even more information about what risks may be out there.
There’s a phase 1 clinical trial that Dr. Rodriguez mentioned that she helps facilitate at her clinic. That is pretty much the first time that these drugs are being used in a single agent or in combination with another chemotherapy or agent.
In phase 2 clinical trials, we have already established that it’s effective or that we can see responses so we want to study a bigger population. We’re seeing more patients now being exposed to the medication to confirm that it works.
In phase 3, we’re doing a much larger trial where we’re comparing it to what’s already considered to be the standard of care. This is the way we treat this, but now we have this new option, and let’s compare the two to see if one is better.
Those eligibility criteria are there to make it safe, although we do know that sometimes they’re too safe that they’re excluding patients who need treatment.
Dr. Estelamari Rodriguez
Eligibility criteria for clinical trials
Terri: Carina asks, “What are the typical eligibility criteria? My mom can’t do trials near her because of her poor ECOG PS and she’s on oxygen.” Give us some guidance.
Dr. Rodriguez: We need to develop trials for real-world patients. Because of their disease, some of them will be on oxygen. Patients will have brain metastases. They’re going to need clinical trials and many trials have excluded them in the past.
I’m very excited about the Pragmatica trial by SWOG; that has no lab requirements. They don’t need to look at your oxygen status. They just need a doctor who has a patient in front of them and they just want to evaluate their response.
We need to encourage more trials that are for patients who need them and have a lot of symptoms. Sometimes, these patients are too sick to go into a trial because they’re new drugs and we really don’t know how they’ll tolerate them or we have serious concerns about toxicity.
You have to trust your doctor that those eligibility criteria are there to make it safe, although we do know that sometimes they’re too safe that they’re excluding patients who need treatment. There is a big movement by the NCI to make trials for real-world patients.
Terri: That’s the direction we need to really go in because we’re real people and we need to have real-world access.
This is the fight of your life. If you’re not open to clinical trials, you’re closing your eyes to opportunities.
Dr. Estelamari Rodriguez
Final takeaways
Terri: What is the top takeaway that you hope our audience members leave with when it comes back to clinical trials in lung cancer?
Dr. Rodriguez: Don’t be afraid to ask about clinical trials because if you have a diagnosis of lung cancer where a lot of patients are going to progress, this is the fight of your life. If you’re not open to clinical trials, you’re closing your eyes to opportunities.
I always tell patients about those patients who went on immunotherapy trials and are alive 10 years later. It was as scary as the trials that we’re talking about now, too. No one knew that drug would work and look what happened. That drug worked and made a difference. It changed lives.
I want to give people the sense of hope that clinical trials offer hope. People who do clinical trials do get better outcomes because they’re monitored very closely for risks. Clinical trials give you an opportunity to do better and really push the envelope in a disease that can be relentless.
Dr. Porter: Clinical trials are very important. I would love for patients and caregivers to take away the need for biomarker testing. I know that we’ve heard it over and over again, but I don’t think we can express that enough because most of the clinical trials are biomarker-driven trials.
In order to find out if a patient is going to be a candidate for a trial, we have to have their initial biomarker testing done. Not only do we increase the likelihood of them getting a relevant first-line therapy, but we also increase the likelihood that at the time of progression, we will have a good clinical trial that may be available for them.
As patients, make sure you’re asking, “Did you do my biomarker test? What does my biomarker test say?” We can’t ask that enough. If you’re at the clinic with someone who’s been diagnosed with lung cancer or any cancer, ask, “Have you done any biomarker testing?”
As providers, it holds us accountable so that we make sure that we’re doing that for patients. We can then give them a good first line of standard of care and good clinical trial options when a clinical trial is not appropriate in the first line.
Terri: You need to know what you are so that you can take charge of what you’re doing because you’re the patient in this and it’s your skin in the game.
Stephanie: Thank you, Terri, Drs. Porter and Rodriguez. It’s so clear you’re so driven to help patients and their families. Thank you for the amazing conversation. We hope to see you at a future program.
Join us as a panel of CLL experts featuring Dr. William Wierda, MD, Ph.D., from MD Anderson, Dr. Nicole Lamanna, MD, from Columbia University Medical Center, Dr. Adam Kittai, MD, from the Ohio State University, and Jackie Broadway-Duren, PhD, DNP, APRN, FNP-BC, from MD Anderson, converge to delve into the most recent developments in CLL research, clinical trials, treatment approaches, and holistic care strategies.
With patient advocate moderator Jeff Folloder, The Patient Story strives to bridge the gap between medical expertise and the lived experiences of patients. This inclusive discussion fosters a truly comprehensive dialogue that empowers, informs, and inspires hope. Join us on this enlightening journey into the world of CLL, where science meets the human experience.
Thank you to AbbVie & BeiGene for their support of our patient education program! The Patient Story retains full editorial control over all content. This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
My name is Jeff Folloder. I’m a passionate, patient advocate. I do this often and passionately because I want everyone to know that it is not just possible to live a good life with CLL, it’s possible to live a great life with CLL.
A little over 13 years ago, my first doctor diagnosed me with CLL and in a very brusque way informed me that I have six years to live. Sounds fun, right? I fired him.
I wound up at MD Anderson and my doctor at the time, Dr. Michael Keating, picked me up out of the chair, gave me a big giant hug, and said, “You’re going to die with this not from this,” and that felt good.
I had the honor to speak at his retirement gala and he pulled me off to the side and said, “I’m changing my mind. We’re going to cure you.” That had a lot of gravity.
Why do I think that it’s possible to live a great life even with a CLL diagnosis? I’m doing everything that I want to do with my life and not at a low level — at a really loud volume level. I’m a better father, a better husband, and a better friend. I’m doing everything that people who don’t even have a cancer diagnosis could dream about doing.
I’m training to do the Bataan Death March Memorial Marathon in March 2024, which is held in the high desert of New Mexico. I’ll be over a mile up doing 26.2 miles off-road. I pound out the miles every morning. I love doing it. Do I have the typical CLL patient fatigue? You bet, except mine’s self-inflicted.
My doctor right now is Dr. Wierda. Every time I see him, he asks me why I worry so much. I shouldn’t worry, but I do.
I want to thank our sponsors, AbbVie and BeiGene. This program is not medical advice. You’re here to learn. Anything specific about your condition and your treatment should be discussed with your doctor.
Dr. William Wierda: My background is in immunology. I have a Ph.D. in immunology and I’ve always been interested in immunology.
CLL is a unique disease from an immunologic perspective. As a fellow, I was working with Tom Kipps at the University of California San Diego and trained with him. I was doing immune-based treatment strategies and that was the beginning of my interest in CLL and why I have stuck with CLL for many years. Then Michael Keating recruited me to Anderson. He is somebody who’s inspired me for many, many years with my work in CLL.
Dr. Nicole Lamanna
Dr. Nicole Lamanna: Michael’s also been a mentor of mine for years, too. I enjoyed taking care of the whole patient so I was inspired by leukemia mentors at Memorial Sloan Kettering when I was an intern and a resident. Because of that aspect of handling the entire patient, acute leukemia and leukemia, in general, became a passion of mine.
I wound up doing my fellowship and staying in leukemia ever since. Chronic lymphocytic leukemia affects not just the blood but your whole body and many different organ systems and your immune dysfunction. I like handling the whole patient and that’s why I’ve stayed in CLL.
Dr. Adam Kittai
Dr. Adam Kittai: I enjoy seeing my patients longitudinally over time. With CLL, it’s a disease our patients live with for a long time. It’s a pleasure for me to get to know my patients, get to know about their families, and see them throughout their lifetime.
Jackie Broadway-Duren
Dr. Jackie Broadway-Duren: When I first came to MD Anderson, I worked with acute leukemias and it became so emotionally overwhelming. Dr. Keating seized the opportunity and recruited me to work with his CLL team.
CLL patients are very unique. You get to follow them for a long time. You get to know their families and you become a part of their families. Most importantly, this is the leukemia that has some of the most exciting treatments currently available and on the horizon so that’s why I stayed with CLL.
Current CLL Treatment Options
Jeff: Dr. Wierda, when I first started, there was one choice. What has happened?
Dr. Wierda: In the last 10 to 15 years, the evolution of targeted therapy for patients with CLL has changed the natural history of the disease and impacted survival. We’ve developed oral agents that are extremely effective at controlling the disease, like the BTK inhibitors and venetoclax, a BCL2 inhibitor.
We’re working on optimizing how to use those and how to work with them to develop curative therapy. The landscape has changed remarkably over the last 10 to 15 years. We’re not giving chemotherapy anymore, which used to be the standard treatment. We have highly effective treatments that are very well tolerated.
In the last 10 to 15 years, the evolution of targeted therapy for patients with CLL has changed the natural history of the disease and impacted survival.
Dr. William Wierda
Jeff: That sounds great. But, Dr. Lamanna, have we left chemo on purpose?
Dr. Lamanna: Regimens like fludarabine, cyclophosphamide, and rituximab or FCR, which Dr. Keating championed, were very effective regimens. It’s just that they had a whole host of side effects and were less targeted.
There are patients in different parts of the world who still get these therapies because they may not have access to these newer agents. We have more focused, better therapies that have fewer side effects and deal with the biology more precisely so we’ve moved away from chemoimmunotherapy.
Targeted Therapies
Jeff: Dr. Kittai, can you tell us about these targeted therapies? What are they doing and why are they so important to patients today?
Dr. Kittai: Ibrutinib, acalabrutinib, and zanubrutinib are Bruton’s tyrosine kinase (BTK) inhibitors.
Bruton’s tyrosine kinase is an essential messaging protein that allows the CLL cells to survive. These three drugs target Bruton’s tyrosine kinase and prevent it from working. It’s an essential pathway within the B cell receptor that activates the CLL cells. The BTK inhibitors inhibit that specific protein to prevent the CLL cells from dividing and living a long time.
Currently, the only approved BCL2 inhibitor is venetoclax or VENCLEXTA. Cancer cells like to increase signals that allow them to live longer and avoid dying. Our mitochondria are the powerhouse of the cell. Two balances live on top of it. There’s the I’m-going-to-die balance and the I’m-going-to-live balance.
Cancer cells like to increase the I’m-going-to-live balance. Venetoclax corrects that and increases the I’m-going-to-die balance. It leads to an equilibrium improvement for our CLL cells, allowing for the drug to work and treat the CLL.
We’re not using PI3K inhibitors, like idelalisib, as much as we used to. They also impact the B-cell receptor pathway, which is another way that the cells divide. PI3K inhibitors work very similarly to BTK inhibitors, but a different molecule altogether.
Jeff: Dr. Broadway, you’ve been watching patients go through this evolution. They started with very narrow choices. We revolutionized things with FCR and similar treatments and now we’re moving on to targeted therapies. How are patients responding to this new mode?
Dr. Broadway-Duren: Patients are loving the oral therapies. Many of them reported feeling like they can play golf for the first time in years because they have the flexibility now. These medications are taken at home so it frees them up to do more activities. No one wants to sit in a chair for hours for chemotherapy nor do they want to deal with the side effects of chemotherapy.
I clearly remember when ibrutinib was about to be approved and we were anxiously awaiting the approval of ibrutinib. We had phone calls months ahead of time. People wanted to be on the first studies that we had for ibrutinib. It has revolutionized the care for CLL.
These drugs are not without side effects, but they are tolerable and we can work through them with the patient. It takes a multidisciplinary approach, but this is certainly a better option for patients than chemotherapy.
BTK Inhibitors
Jeff: I’m in watch and wait again. I started over 13 years ago.
I went through a clinical trial at MD Anderson where I used a single-agent immunotherapy drug. Although that drug is no longer front line, other immunotherapy drugs are still being paired with some of these new treatments.
Dr. Wierda: The ALPINE and ELEVATE trials are randomized phase 3 clinical trials. Those look at one BTK inhibitor versus another. Both trials compare a second-generation BTK inhibitor against ibrutinib, which is the first-generation BTK inhibitor.
Those trials demonstrated an improvement in tolerability with the second-generation BTK inhibitors over what has been the standard long-term, which is ibrutinib. There are more cardiac toxicities with ibrutinib compared to the second generation.
Those trials compared two treatments and showed that the tolerability and toxicity are a bit less with the second-generation inhibitors compared to ibrutinib. There’s some suggestion that zanubrutinib on the ALPINE trial may have a better progression-free survival.
The ALPINE and ELEVATE trials demonstrated an improvement in tolerability with the second-generation BTK inhibitors over what has been the standard long-term, which is ibrutinib.
Dr. William Wierda
The follow-up is different in both trials. The patient population is different. They demonstrate that the second generation is preferred over the first generation. I don’t think you can make any conclusions between the different second-generation BTK inhibitors, acalabrutinib versus zanubrutinib.
Other phase 3 randomized trials compare different treatments, like iLLUMINATE. Those trials look at chemoimmunotherapy, which has been the long-term standard, versus targeted therapy. They’re predominantly BTK inhibitor-based treatments using first-generation and second-generation BTK inhibitors.
A number of those trials have clearly shown improvement in progression-free survival with oral BTK inhibitors over chemoimmunotherapy. A couple of trials have shown survival advantages if you start with a targeted therapy.
BTK Inhibitors + Venetoclax
Jeff: Dr. Lamanna, one of the things that’s been combined is ibrutinib with venetoclax. Does it work well? Why is it approved in Europe and not the US?
Dr. Lamanna: Yes. As Bill alluded to, there are lots of studies that have shown the benefit of these agents over chemoimmunotherapy. We’re trying to look at different combinations to see if we can tweak these therapies better. There are oral-oral combinations of BTK inhibitors plus venetoclax.
Many trials are looking at ibrutinib and venetoclax, acalabrutinib and venetoclax, or zanubrutinib and venetoclax. There was a study in Europe called the GLOW study that looked at ibrutinib and venetoclax versus more traditional chemoimmunotherapy with chlorambucil and obinutuzumab. Chlorambucil and obinutuzumab are not used as much in the US anymore, but it was a gold standard for older frailer patients with CLL as a standard chemoimmunotherapy regimen.
Nobody was doubting that the ibrutinib-venetoclax arm would be better. There were some toxicities from this regimen. Based on the combination of ibrutinib and venetoclax from this GLOW phase 3 randomized study, this was approved as a regimen in Europe.
Even though ibrutinib is a great drug and it’s done well for our patients, the newer generations have fewer side effects.
Dr. Nicole Lamanna
There are different regulatory boards here versus in Europe. Our regulatory boards want us to look at some of the newer generations, acalabrutinib or zanubrutinib, with the oral-oral combinations and some of our phase 3 studies before this oral-oral combination gets approved. Ibrutinib and venetoclax are not approved in the US yet.
Because of those head-to-head studies of ibrutinib versus acalabrutinib or ibrutinib versus zanubrutinib, we’ve seen that the newer generations of these BTK inhibitors have fewer cardiac toxicities.
Even though ibrutinib is a great drug and it’s done well for our patients, the newer generations have fewer side effects. Because of that, partnering with a newer agent that may have less toxicity is probably where the FDA will want to go versus ibrutinib.
Time-Limited Therapy vs. Continuous Therapy
Jeff: We started with treatment programs that were broad brushes. With these trials, we’re narrowing the focus so that instead of treating all CLL patients with one regimen, we’re paying attention to what kind of CLL we’re talking about and what would be the best, personalized care. Is that a fair statement?
Dr. Kittai: That’s a fair statement. We don’t know if BTK inhibitors are better than venetoclax plus obinutuzumab. There hasn’t been a randomized phase 3 trial to tell us that this approach with time-limited therapy is better than continuous therapy.
If we don’t know which way is better, it comes down to a lot of different factors that are patient-focused, like comorbidities and the risk of CLL.
One of the biggest things that helps me decide what to give my patient is my patient. When we’re talking about time-limited therapy versus continuous therapy, a lot of our patients have a specific want of either of those options. Ultimately, it comes down to a conversation of the pluses and minuses of each regimen, which certainly is patient-specific and patient-focused.
There hasn’t been a randomized phase 3 trial to tell us that this approach with time-limited therapy is better than continuous therapy.
Dr. Adam Kittai
For instance, continuous therapies are generally very well tolerated. After I start a BTK inhibitor, I see my patients two weeks later to make sure everything’s okay, one month after that, and then every three months after that so it’s an easy start-up.
Whereas with the venetoclax plus obinutuzumab time-limited therapy, the patient has to come into the clinic weekly for the first two months. We have to do a little bit more monitoring because the cell counts can get a little low, but everybody gets a stop after a year.
If you have someone younger, who has an active lifestyle, and who can’t get off work to come into the clinic once a week, they may opt for continuous therapy. A similar person who can’t see themselves taking a pill for so long may opt for time-limited therapy because they want to get it done with.
Each patient is different. Now, we have a lot of different options to use.
Jeff: Let’s talk about some of these clinical trials, which are giving us even more options. We’ve got the CLL17 trial, the ALLIANCE trial, and pirtobrutinib there. There are a couple of trials going on there.
I noticed we’re not talking about pairing. We’re talking about triplets as well. Tell us what’s going on and why patients need to be aware.
Dr. Kittai: BTK inhibitors haven’t been compared to time-limited therapy to tell us what to pick and which is better so that’s why all of us are excited about the CLL17 trial. This is a randomized phase 3 trial that compares continuous ibrutinib versus time-limited venetoclax plus obinutuzumab versus time-limited ibrutinib plus venetoclax.
Hopefully, we’ll have a better understanding of which way to go for our patients in terms of what might be the most efficacious and safest option because we don’t know how this trial is going to pan out.
As Dr. Lamanna alluded to, when we thought of the GLOW trial, we were pretty sure that ibrutinib plus venetoclax would beat chlorambucil plus obinutuzumab. With the CLL17 study, I honestly don’t know. We’re excited to see how that trial goes. Unfortunately, it’s going to be some years before we find out.
We don’t design trials with a new treatment that we don’t expect to be better. We always think that they’re going to work.
Dr. Adam Kittai
The ALLIANCE trial is ibrutinib plus obinutuzumab versus ibrutinib plus obinutuzumab plus venetoclax. Similarly, a lot of us thought that the ibrutinib-venetoclax-obinutuzumab combination was going to be more toxic than the ibrutinib plus obinutuzumab because, in general, when you add more drugs to a regimen, the toxicity generally increases.
But with a time-limited therapy, the toxicity outweighs the efficacy benefit that you might get from the triplet combination. At ASCO, my mentor Dr. Woyach presented the study because it had to end early. More patients died on the triplet arm, which we were all surprised about.
Ultimately, we had to see how this plays out long term. COVID was a true impact here. Unfortunately, more patients passed away from COVID on the triplet arm. If you take out those COVID deaths, it does look very similar so we’ll see how this plays out long term.
We don’t design trials with a new treatment that we don’t expect to be better. We always think that they’re going to work. Ultimately, what this tells us is that we have to roll our patients onto clinical trials so we can get better answers to the questions that we have.
When we enroll patients in clinical trials, we can follow them forward in time to get the data that we need so we can share the results with the community at large.
We think about the different aspects of your disease, yourself, and other medical problems when we talk about your options for therapy.
Dr. Nicole Lamanna
Jeff: How does one choose between time-limited and continuous therapy?
Dr. Lamanna: As Dr. Adam suggested, this can be a lengthy discussion. We look at disease characteristics, but we’re looking at other factors, too. We’ll take into consideration your comorbidities.
Different drugs have different side effect profiles. BTK inhibitors and venetoclax are two oral agents that are both very effective, but, as said before, we don’t know that one is necessarily better than another.
We take into consideration patient considerations. Do you want to do something that’s time-limited and more intense initially? Can you afford to do that and be ever-present, particularly in the beginning when there are more side effects?
Part of it is the circumstances of the patient but also the side effects of the drug and what medical problems you may have, what other medications you may be on for these other medical problems, whether or not there are drug interactions, and how we overcome some of those issues, depending upon the drug.
It winds up being a very long conversation when we think about the different aspects of your disease, yourself, and other medical problems when we talk about your options for therapy. The good news is now there are a lot of different options, which weren’t available before.
CAR T-cell Therapy
Jeff: Dr. Broadway, one of the things that was very exciting and talked about in the CLL community was CAR T-cell therapy. Frankly, from my perspective, it was intimidating. It sounded pretty dramatic. What goes on with CAR T?
Dr. Broadway-Duren: In our immune system, we have B cells and T cells. B cells generally help provide immunity. T cells naturally release cytokines that can kill off things that shouldn’t be there.
With CAR T-cell therapy, the principle is that they would extract your cells, send them to a lab, and incubate them with CAR T cells, which have a natural killer instinct so that the T cells then recognize CLL cells and learn to fight against them. They expand these cells in a laboratory setting so that they can get enough of them and give them back to you as they would with a stem cell transplant.
Jeff: Dr. Wierda, this sounds great. Why aren’t we doing this for everybody?
Dr. Wierda: Not everybody can tolerate it very well. There are toxicities associated with CAR T-cell therapy. I’ve been working in the CAR T cell area for many years and we have seen data that dates back many years ago. Carl June and his group treated patients with CAR T cells many years ago.
Many patients have been cured by CAR T-cell therapy. Not all of them are cured. The side effects and toxicity profile are difficult for some patients. When patients get sick, they require hospitalization. Some patients end up going to the intensive care unit.
The CAR T work began with CLL years ago and that product has leapfrogged for patients with acute myeloid leukemia and DLBCL. That scenario illustrates some of the challenges. It’s not as effective in patients with CLL and some side effects and toxicities are a bit higher in patients with CLL compared to other diseases.
While the story started with CLL, we’re still catching up. I think we will have a product that’s approved. We worked on the TRANSCEND study and I anticipate that there are patients who have been in remission who have probably been cured of their disease. But logistically and from a toxicity perspective, it’s a little bit harder to work in patients with CLL.
Very successful in other diseases so I think that it will move along in CLL and get approval.
Dr. Nicole Lamanna on CAR T-cell therapy
Jeff: That sounds reasonable and prudent. I would guess that you’re hedging a little bit. Maybe those toxicities are probably a little bit intense.
Dr. Lamanna: We started working on CAR T cells when I was at Memorial. It was one of the first studies and so this is going back over a decade ago. The reason, in part, why it’s been slower in CLL is because, in those other cancers where it is approved, they had fewer therapy options.
We’ve had all these wonderful targeted therapies that have become available. Whether it’s fortunate or not fortunate, CAR T-cell therapy got relegated to multiple relapsed patients.
We have a lot more experience using CAR T because it’s been around now for over 10 years. We’ve improved on some of the side effects. In some of the early CAR T-cell clinical trials, some patients passed away from the therapy. We’re learning how to mitigate some of the toxicity.
There have been some very good results from studies, such as the TRANSCEND study. I think we will get approval. I think it’ll be in the relapsed setting. It may move up as we use it in combinations for certain individuals. It has some activity in some of our refractory patients, patients with Richter’s syndrome, for example, and patients whose CLL has transformed into a more aggressive lymphoma.
There are important uses for CAR T cells. It’s a different type of modality using your immune system to attack your CLL cells. Very successful in other diseases so I think that it will move along in CLL and get approval. It’s just that we also have the benefit of having so many other agents. We’ll see ultimately where it fits in the grand scheme of things. Right now, in the relapsed/refractory setting is an important option.
Dr. Kittai: We have three types of clinical trials. We have phase 1 trials, phase 2 trials, and phase 3 trials.
Phase 1 trials are first in human or dose finding. They’re usually very small, under 50 patients. They’re looking for a dose and safety of the drug.
Phase 2 is meant to find the initial efficacy and how well it works.
Phase 3 is usually how a drug gets approved. You’re comparing the new intervention versus something that we’re already doing. The patient is randomized to two arms and the ultimate goal is to find out whether or not the new drug works better than the standard of care.
TRANSCEND study is a phase 2 study. It was a single-arm study that looked at patients who received BTK inhibitors and BCL2 inhibitors so that’s the ibrutinib-acalabrutinib-zanubrutinib or venetoclax.
Patients had been treated with our main lines of therapy and so it looked like if you responded to the CAR T-cell therapy, you did well.
Dr. Adam Kittai
You get CAR T-cell therapy one time. You get the blood taken out of you, it gets sent to the manufacturer, and the CAR T cells get infused back. Once the product is available, you get chemoimmunotherapy to make it easier for your cells not to reject the CAR T cells that you’re about to get.
We have to follow you pretty closely for 30 days. Liso-cel happens to be the safest of the three that are currently approved right now for non-Hodgkin’s lymphoma.
We’re looking for ways to mitigate the toxicity associated with CAR T-cell therapy. The interesting way that we’re doing that is with BTK inhibitors concurrently with the lysis cell, giving steroids before giving various other agents to try to mitigate the toxicity.
For the TRANSCEND study, which accrued about 100 patients, of the patients who got the product, only about 80 got undetectable minimal residual disease responses so that means that they weren’t able to detect the CLL in these patients.
These patients had been treated with our main lines of therapy and so it looked like if you responded to the CAR T-cell therapy, you did well. Unfortunately, there were some nonresponders and that’s classic with CAR T-cell therapy. If you respond, you do well and if you don’t respond, you don’t do so well, which makes sense, too.
In general, this was a high-risk group of patients who received all of our primary lines of therapy with this one-time therapy and there was a response rate of 60%. Hopefully, based on this phase 2 study, it gets accelerated approval, which means that you only have approval for a few years. The phase 3 studies will come down the line hopefully.
Obinutuzumab + Venetoclax
Jeff: Dr. Jackie, what do patients find most challenging in tolerating the OV treatment side effects?
Dr. Broadway-Duren: One of the things that they find challenging is the immediate effects. After getting an obinutuzumab infusion, they may have reactions within the first 72 hours. They may run a fever. We educate the patients well so that they’re not surprised that they may experience some fever, chills, or changes in blood pressure during the infusion.
With venetoclax, the most reported side effect I’ve heard is diarrhea and that’s something we work through with the patient. As a provider, we look at the toxicity of neutropenia. This doesn’t happen in everyone, but there is some degree of neutropenia.
Venetoclax is a once-a-day dosing. Sometimes they find it challenging to get all four tablets in when they reach the full dose capacity for the drug.
The greatest is GI side effects, primarily loose stools. We prepare the patients by telling them ahead of time. There are medications that they can buy over the counter or a prescription strength anti-diarrheal medicine they may need.
Bispecific Antibodies
Jeff: Dr. Bill, we’ve talked about the mabs and the ibs. Bispecifics is a new variant I have to learn.
Dr. Wierda: Bispecifics are antibodies, which we have used for years in CLL; rituximab being the first one. We have obinutuzumab, which has been mentioned.
Monoclonal antibodies bind to certain proteins. They identified proteins on CLL cells that they could target. CD20 is the target for rituximab and obinutuzumab. Alemtuzumab, which is a drug used years ago that we don’t use anymore, targets CD52.
Bispecifics are engineered molecules that target some of those proteins and are linked to an antibody that targets a protein on your T cells called CD3. The bispecific binds CD20 on the CLL cells and CD3 on the T cells of your immune system. When those two cells come together, the molecule will trigger the T cell to attack the CLL cell and kill the CLL cell.
These drugs are approved now for non-Hodgkin’s lymphoma, but we don’t have any approved for CLL yet. There are several clinical trials right now that are studying bispecifics.
Epcoritamab is one of the bispecifics that’s already approved but not for CLL. It’s under investigation for patients with relapsed CLL and Richter’s transformation. This is a category of medications I’m very optimistic about. We have heard preliminary data demonstrating activity in treating CLL with these compounds.
There’s a little bit more work we need to do in this area in terms of optimizing the efficacy and making it a better, well-tolerated treatment for our patients, just like CAR T cells.
Dr. Lamanna: Bispecific antibodies have more similar side effects to CAR T because of the link to the CD3 or the T-cell activation so we need to work on that.
Jeff: This is exciting. Dr. Wierda, we had a conversation about a year ago in the clinic and you gave me a new perspective. You told me that the goal of the staff and the team at MD Anderson was to keep me alive. The longer you kept me alive, the better the drugs would be when I needed them.
That was an “Aha!” moment for me because the first drugs that I had to choose from weren’t great. I wasn’t a big fan of the toxic profile and the side effects. I joined one of your clinical trials and got great results, and we weren’t even using that drug for CLL anymore.
There are always things on the horizon. I recommend patients look for clinical trials.
Dr. Adam Kittai
Treatment for Relapsed/Refractory CLL Patients
Jeff: Dr. Adam, some patients aren’t able to tolerate some of these treatments. What happens when we’ve tried different treatments and the outcome is not looking great; what’s next on the horizon?
Dr. Kittai: For standard CLL, the area of unmet need is patients who have received BTK inhibitors and BCL2 inhibitors, and have progressive disease after that, or if they’re not able to tolerate either of those two medications.
CAR T-cell therapy is on the horizon. There are also new BTK inhibitors and new BCL2 inhibitors coming out as well.
As Dr. Bill said, we are having an explosion of options for our CLL patients and we do expect a lot of these drugs to get approved. One that is as close to approval as you can get is pirtobrutinib and I expect it to be approved as an accelerated approval any day now.
Pirtobrutinib is a BTK inhibitor — like ibrutinib, acalabrutinib, and zanubrutinib — that was designed specifically to bind a little bit differently to the BTK protein, allowing it to work when the ibrutinib, acalabrutinib, and zanubrutinib stop working.
The first second-generation BTK inhibitors are what we call covalent BTK inhibitors (cBTKi). Pirtobrutinib is a non-covalent BTK inhibitor (ncBTKi). We’re starting to call pirtobrutinib our third generation. There are new BTK inhibitors, but the degraders are coming out. There are covalent/non-covalent BTK inhibitors so we’re now having fourth, fifth, and sixth-generation inhibitors.
Pirtobrutinib will likely be approved. It looks like a safe drug and is an option for patients who are refractory or cannot tolerate the two other medications.
There are always things on the horizon. I recommend patients look for clinical trials, but we will soon have two drugs approved for these patients specifically.
Jeff: Sounds promising and exciting.
Watch & Wait
Dealing with Fatigue
Jeff: Dr. Lamanna hates the term watch and wait. Patients, call it watch and worry. We’ve got cancer. We’re supposed to be doing something about this.
Dr. Jackie dealt with more watch and wait complaints. I remember coming in and you asking me, “How are we feeling today?” I would tell you I’m fatigued and you would make me go through the litany of what fatigue is. We had to figure out the difference between tired and fatigued.
We know that watch and worry is a heavy burden that we carry. No matter what all of you guys say, we’re still going to watch and worry. Is fatigue normal during watch and wait?
Dr. Broadway-Duren: Fatigue is normal with CLL in general. It’s normal to have a degree of fatigue as you’re watching and determining when it’s time to institute therapy.
When we’re trying to make a decision, I always try to reiterate to patients the optimal time to start treatment or if and when they need treatment.
It’s difficult. When a patient comes in, they may have a white blood cell count of 60,000. In their mind, they think that they need to get treated when, in fact, they have a good quality of life.
It’s normal to have a degree of fatigue as you’re watching and determining when it’s time to institute therapy.
Dr. Jackie Broadway-Duren
There’s underlying fatigue so we try to get them to do things that may improve their fatigue, such as exercise. It’s important to find out other factors that may be contributing to fatigue. It may not always be CLL.
We’re monitoring everything very, very closely. There’s no set number in which we decide it’s time to treat a patient.
You’re going to have some degree of fatigue, but we try to work through it. When you have levels of fatigue where you need to go back to bed by 10 a.m. when you just got up at 8 and there are other things like night sweats, then maybe that’s the time to start looking at treatment options.
Jeff: One of the things that Dr. Jackie made sure I understood when I was reporting my fatigue was if I get refreshed from that sleep. Do I get refreshed from that nap? More importantly, is my fatigue impacting my ability to do the things that I want to do in life? Those are very important questions to ask yourself and they’re very important answers that you need to give to your medical providers. They need this insight into what’s going on with you so that they can help you make good decisions.
Our treatments are evolving. What’s available today is going to be different than what’s available in a year, and it’s going to be better in a year.
Dr. William Wierda
Jeff: Dr. Bill, I’m in watch and wait for a second time. How long do I need to be there?
Dr. Wierda: Until you need to be. There have been several clinical trials done to determine whether or not there’s a survival benefit with early treatment.
Take 100 patients who are newly diagnosed and don’t otherwise need treatment. Half of them get early treatment while half of them don’t.
Those trials have not shown a benefit with early treatment versus watch and wait. That’s very important. We worry but it’s not to the detriment of your survival to wait and to move to treatment when you need treatment.
Our treatments are evolving. What’s available today is going to be different than what’s available in a year, and it’s going to be better in a year.
Treatment improves with time and you have to have some comfort and confidence in that. I’m a professional worrier. Let me worry for you. That’s my job. I’m serious about that.
Jeff: It’s not a joke. All my life, I have been a professional worrier. We have a little bit of agitation between the two of us because the week before my regular checkup at MD Anderson, I get wound up. I’ve been doing this for a long time. I know exactly what’s going to happen. I know exactly how the blood draws are going to work. I know exactly the rate at which the results are going to start pinging on my phone so I can get an idea of what’s going on.
Even though I know all of this, and I know it’s more than likely that the answer at the end of my clinic visit is, “See you in six months,” I worry. I get agitated. I obsess over it.
One of the things that I do is pound out more miles. You’re not supposed to do a half marathon before a blood draw and you’re not supposed to do it a second time. Pro tip: drink more water.
Some patients never need treatment for their CLL and it would be great if we could draw their blood and know exactly who they were because then they would never have to get any therapy or be exposed.
Dr. Nicole Lamanna
Dr. Lamanna: This is truly a chronic illness, although everybody is trying to find curative therapy for CLL. We want you to enjoy your life.
I don’t like watch and wait. I do active observation and monitoring; that’s what I call it. We’re not trying to take away the worry and the concern.
Watch and win’s a great one because as you’re sitting on the sidelines, all these new therapies become available and it changes the standard of care.
Patients get the benefit of sitting on the sidelines as new therapies, guidelines, and changes are happening because of all the research that we’re doing. What might have been used five years ago may be very different from what’s used tomorrow. You gain the benefit of that without going through all the pain.
Some patients never need treatment for their CLL and it would be great if we could draw their blood and know exactly who they were because then they would never have to get any therapy or be exposed. For everybody else, if we had curative therapy, then we’d be giving it to everybody.
It doesn’t take away the anxiety or the worry, but you need to fill that with other things in your life.
If you have other chronic medical problems, like high blood pressure, diabetes, or heart disease, that you’re actively taking medications for, you’re doing something about it every day.
With CLL, if you’re not, you’re not. It doesn’t mean you don’t have a problem. You just don’t need any active therapy right now. It’s an important distinction and I wish people could think about things a little differently.
We need to couch it a little differently so patients can deal with it psychologically a little differently.
You may not be getting treatment for your CLL, but in a way, you’re actively treating yourself because you’re delaying the treatment that might be better when you need treatment.
Dr. Adam Kittai on watch and wait
Jeff: Dr. Kittai, in your practice, what are the thresholds that get people out of watch and win?
Dr. Kittai: I want to validate all of the symptoms that patients have on watch and wait. It’s usually these low-level symptoms. I want to make sure that everyone knows that it is normal to have symptoms on watch and wait.
One of the studies that Bill mentioned was early treatment with ibrutinib versus placebo. The most surprising thing about this trial for patients who typically would have been on watch and win was that the patients randomized to placebo had a higher symptom burden than all of us expected.
It’s normal not to feel 100%. You may not be getting treatment for your CLL, but in a way, you’re actively treating yourself because you’re delaying the treatment that might be better when you need treatment.
For someone to require treatment based on a symptom, the symptom has to cause so much distress that it causes the patient to not have the ability to enjoy their life.
Dr. Adam Kittai
Deciding When to Start Treatment
Dr. Kittai: There are two types of indications to treat. There are subjective factors, which are the symptoms, and objective factors, which are laboratory values and big lymph nodes.
The objective indications are hemoglobin, which is your red blood cells, less than 10 or a rapidly dropping hemoglobin, a platelet count less than 100, a spleen size that is larger than 6 cm below the left costal margin, and lymph nodes greater than 10 cm.
These objective indications are pretty extreme, I would say. I typically don’t let my patients get up to that level. We typically try to treat right before, but we see it coming. You do need to have one of those indications to treat.
The other indications to treat are going to be symptoms. Those are the classic B symptoms, like fatigue, night sweats, fevers and chills, and weight loss. These symptoms typically worsen as the objective signs worsen so they usually go hand in hand. Sometimes symptoms and objective indications are out of proportion so sometimes they’re a little discordant.
Every patient is a little different. For someone to require treatment based on a symptom, the symptom has to cause so much distress that it causes the patient to not have the ability to enjoy their life. I don’t like my patients to get to that point. I try to do it right before they’re miserable because I don’t think that’s fair.
Live life the best you can. I know it’s not easy, but get up every day and try to focus on something positive in your life.
Dr. Jackie Broadway-Duren
Jeff: Dr. Jackie, we’ve been talking in a very clinical fashion about what’s going on with all the new stuff with CLL. “I was diagnosed five years ago and I’m still in watch and wait. I feel like I’m in limbo. What can I do to live normally and not think about it ever?”
Dr. Broadway-Duren: I know patients are worried and concerned. One thing I found helpful is to sit down with each patient and go through their prognostic factors.
They need to understand what their FISH test means. If you tell a patient you have a negative FISH, they look at you like you have two heads. But if you say to them, “These are the chromosome abnormalities that we look at for patients with CLL. You have no abnormalities,” that encourages them.
When you look at mutational status and other prognostic indicators, if all those things are favorable, talk with the patient and explain to them that it’s unlikely that they’re going to have a rapid progression of CLL. It doesn’t mean they won’t ever need treatment, but I think that helps allay some of the fears and anxiety that they have.
The only thing you can do is go about your life as best you can. Try to focus on other things, whatever it takes to keep you busy and keep your mind occupied.
The worst thing you can do is sit at home every day and get on Google and some of these CLL blogs. Some of them are helpful but some of them are not because of erroneous information.
Find a good factual website. Use LLS. If you want to hang out with people, get in with someone who has the facts and who will give you appropriate information.
Live life the best you can. I know it’s not easy, but get up every day and try to focus on something positive in your life.
Health maintenance falls into two categories. One is infection prevention, the other is early detection of other cancers.
Dr. William Weirda
Dr. Wierda: Part of the challenge with watch and wait is that patients feel like they’re not doing anything actively for their health. I spent a lot more time in recent years talking about health maintenance.
Our patients are often living a normal life span as if they didn’t have CLL, but oftentimes we struggle with some challenges with the disease, even if they’re in remission. Their immune system doesn’t work normally.
Health maintenance falls into two categories. One is infection prevention, the other is early detection of other cancers because other cancers occur more frequently in patients with CLL than in the general population.
Infection prevention means making sure you’re up to date on all your vaccinations. It’s a very important area that patients can actively participate in.
Early detection for other cancers involves going to a dermatologist for regular skin cancer screening, annual mammography and pap smears for women, prostate cancer screening for men; and colon cancer screening. I would try to direct the conversation to that aspect because those are things you can do that are important for our patients.
The hardest part of starting an exercise program is the first step. The second one’s easy. The third one’s a piece of cake.
Jeff Folloder
Jeff: Do the things that your GP wants you to do as well.
Take your blood pressure medicine. Take your cholesterol medicine. Keep your diabetes under control. Work on controlling your weight. Exercise a little more often.
The hardest part of starting an exercise program is the first step. The second one’s easy. The third one’s a piece of cake. Fourth, fifth, and all the rest of them are easy. It’s when you get up in the morning and know that you need to do whatever it is that you’re going to do. It’s taking that first step.
It’s really easy to sit in a chair or the bed and not take that first step. Sometimes all you need is one step so take that first step.
Take that first step with your happiness as well. Pick one thing. It doesn’t have to be big, but one thing that gives you the smallest first glimpse of a smile.
I have worked from home for well over a quarter of a century. Unfortunately, that means that the lines blur dramatically between my work life and my personal life. When I hear the email alert go off, I want to go see it.
At around 5 o’clock, I stop to go to the kitchen, grab a glass, and fill it with ice. Two four-footed furry missiles come flying into our den. I put a little whiskey in that glass, sit down in my chair, and turn on the evening news. Both cats sit right in front of me, waiting for their freeze-dried chicken treat. That makes me smile. That’s something that I can focus on. That’s worth doing.
I’m not focused on my CLL. I’m not focused on a cancer diagnosis. I’m not worried about my white blood cell count, my platelets, and how I sabotaged my glomerular filtration rate by not drinking enough water after exercising. I’m taking those first steps every day.
We know that watch and wait is not a fun way to live. What can we do about it? Make active approaches.
You can be unhappy. You can worry. Or you can find that one thing that makes you smile. You can go take that one step, and that one step turns into a block, and then that block turns into half a mile. Then the next thing you know, like me, you’re knocking out marathons.
We don’t use the word cure very often, particularly in CLL, because for most patients, their disease comes back. But there are patients who I’ve followed for 20 years whose disease hasn’t come back.
Dr. Nicole Lamanna
Cure in CLL
Patient: How are you going to know when we’re cured? Is it going to be all physical symptoms good? Normal blood counts? Is it going to be a clonoSEQ of zero for two years?
Dr. Lamanna: There are some patients now who are theoretically cured. They might have gotten FCR, for example, or some other treatment modality, but the biology of their disease is so good that the disease never comes back.
We don’t use the word cure very often, particularly in CLL, because for most patients, their disease comes back. But there are patients who I’ve followed for 20 years whose disease hasn’t come back so they probably are cured.
Our technology is improving with how to measure minimal residual disease or microscopic CLL cells in your body to different depths of detection. We’re employing a lot of these techniques in the current clinical trials to look at depths of detection and it’s changing and evolving.
In CLL, it takes us longer to show if a treatment regimen is going to improve survival and ultimately cure because we’re going to be following some of this testing, which we’re doing on the clinical trials. These aren’t necessarily mainstream in clinical practice yet because the mode of detection is changing and we’re trying to put these in combinations with the clinical trials that are running. But we’re going to need a long time to show that a particular therapy might be potentially curative.
I’ll argue that depending on someone’s biology, there are, in theory, some of those patients already out there.
Jeff: You hedged that bet very well.
Hopefully, we get to a point where we have some biomarkers that tell us that someone is cured.
Dr. Adam Kittai
Dr. Kittai: I’ve started using the phrase “functionally cured.” In a sense, it rephrases the thought process of cure. If you have somebody who’s on continuous therapy and they are not having any toxicities and their blood counts are completely normal, are they cured? They’re technically functionally cured. I like to say, “I looked at your labs and I wouldn’t know you had CLL if I didn’t know you had CLL.”
Dr. Lamanna: They may still have disease and die from something else.
Dr. Kittai: They’re chugging along on their BTK inhibitor without side effects and doing great. Isn’t that somewhat ideal as well? We don’t like the idea of having to take a pill every day, but to some extent, if you’re not having any side effects and your disease looks like it’s well controlled, I don’t know.
I wonder about the word cure. The easiest answer is we don’t know the answer to that question. Hopefully, we get to a point where we have some biomarkers that tell us that someone is cured, but I think that hasn’t been elucidated yet, even with our most advanced technologies.
More and more data is coming out that if we can’t detect your CLL, that is associated with a longer, progression-free survival and overall survival
Dr. Adam Kittai
Jeff: Here we are at uMRD negative. If someone doesn’t show a single one of their cells in the count, are they?
Dr. Kittai: We don’t know the answer to that question yet. More and more data is coming out that if we can’t detect your CLL, that is associated with a longer, progression-free survival and overall survival, but we don’t know.
Anecdotally, based on another disease type entirely, chronic myeloid leukemia, we know that if you get a patient’s CML down to a low enough level, their immune system takes care of it. A similar concept with CLL is that maybe our immune systems can kick back in and take care of it when we get down to a lower level of detection that we’re just not detecting. We don’t know.
The word cure is tricky. Of course, we’re aiming for a cure. I hope that one day we have a biomarker that securely says this patient will not have a relapse again, they don’t need to be on medication, and they are not more immunocompromised than the general population.
The challenge here is assuming that being in remission and having undetectable MRD assures your immune system is back to normal, but we haven’t seen that.
Dr. William Wierda
Jeff: Dr. Bill, you encourage people to do watchful waiting and careful surveillance and let you do the worrying. Patients are on watch and wait for an extended period. In general, people with CLL are considered to be immunocompromised, correct?
Dr. Wierda: Correct.
Jeff: The longer they’re on watch and wait, the longer their immunocompromised bodies are exposed to the world versus starting treatment so they’re not immunocompromised. How do you balance that?
Dr. Wierda: The challenge here is assuming that being in remission and having undetectable MRD assures your immune system is back to normal, but we haven’t seen that. We’ve done a lot of trials and have many patients who are still immunocompromised, even though they have undetectable MRD status. It takes a long time for the immune system to recover and restore to normal function.
Our future work at Anderson will be dedicated to figuring out things that we can do to accelerate the restoration of the immune function and the immune system. But right now, we don’t see that everybody’s immune system is totally normal even when they’re in remission or have undetectable MRD.
There’s a lot of ancillary work besides treating the disease itself to see how we can make things better for patients with CLL in terms of their immune system.
Dr. Nicole Lamanna
Dr. Lamanna: There’s a lot of heterogeneity in terms of your immune system. Some people’s immune system is not as compromised as another person’s. We’re learning how to figure out which individuals might have a worsened immune system versus somebody else. Some CLL patients never get sick while there are patients who get sick all the time and that’s whether you’re on watch and wait or on active treatment.
There’s a lot that we need to learn in restoration and understanding the heterogeneity in our CLL patient population. You’re all different and not everybody is as immunocompromised as the next person. We need to find out if there are ways that we can help to augment their immune system.
Trials are looking at vaccines or at immunoglobulin in CLL patients to see whether or not they benefit and how we look at decreasing the incidence of infection. There’s a lot of ancillary work besides treating the disease itself to see how we can make things better for patients with CLL in terms of their immune system.
They are different tests that look at different parts of the cancer’s genetics to tell us how high risk the patient is.
Dr. Adam Kittai
Dr. Kittai: A question I get often is how long will I be in watch and wait. There was one study that looked at three different factors: IGHV unmutated versus mutated status, palpable lymphadenopathy, and absolute lymphocyte count greater than 15.
If you had 1, 2, or 3 of these factors, how long would I be in watch and wait for? If you had three factors, typically it was around two years. If you had 2 or 1 factors, it was 2 to 5 years. If you had no factors, it was greater than five years.
I see a lot of people buck this trend, but at least it gives us an idea of what to expect. I hope that everyone bucks the trend, but at least it’s something that we can look at and at least advise our patients. If you have all three of these factors, most likely we’ll need treatment sometime in the next two years. If you have none of those factors, over five years is a time that you’ll probably be in watch and wait.
The prognostic factors that we look at in patients with CLL are IGHV mutated status, FISH, which stands for fluorescent in situ hybridization, cytogenetics, and next-generation sequencing. They are different tests that look at different parts of the cancer’s genetics to tell us how high-risk the patient is.
Our normal white blood cells go through hypermutation where they get programmed to attack the very specific bacteria or virus.
Whether the CLL cell comes from the pre-program or after the program determines prognosis, which is interesting. If it comes pre-programmed, that’s IGHV unmutated and if it goes after the program, it’s IGHV mutated and is generally considered a favorable prognostic factor.
We look at all of these things together and help our patients understand their prognosis. A lot of that is changing with our new therapies. Some things that we thought were important are no longer important and some of the things that weren’t important are becoming more important. Your physician will help guide you about your risk factors in terms of what to expect for your prognosis.
Do not dismiss anything as being too trivial to discuss because everything is important. They need to know what’s going on. It’s important to communicate.
Jeff Folloder
Jeff: Dr. Jackie, do patients confide in you? Do they tell you the truth?
Dr. Broadway-Duren: They do. Oftentimes, they will tell me or the advanced practice providers things that they don’t want to share with the doctor for whatever reason. Whenever I ask them, they are very truthful.
I want to tag on to what Dr. Wierda said as far as the immune system. I can think of several patients in our clinic who are in remission and still have all these infections so we’re giving them IV infusions of gamma globulin to try to boost the immune system.
Being in remission definitely does not indicate that you have an intact immune system right away. At some point, it may. The patients are very truthful and forthcoming with information when I speak with them.
Jeff: I advocate on behalf of all of the medical providers. When you’re in watch and wait, nothing is off the table. Everything must be on the table. Do not dismiss anything as being too trivial to discuss because everything is important. They need to know what’s going on. It’s important to communicate.
Vaccines and CLL
Patient: Dr. Wierda, is the shingles vaccine okay with CLL?
Dr. Wierda: You should not get the live virus vaccination for shingles. The one that’s used most commonly now, SHINGRIX, is not a live virus. It’s two doses separated by 2 to 6 months. You should not get live virus vaccinations if you have CLL.
In general, we favor continuous therapy for patients with deletion 17p.
Dr. Adam Kittai
17p Deletion
Patient: Ten years ago, the FISH test seemed to be a big deal and if one had 17p deletion, you didn’t have much time left. Is 17p deletion worse than anything else now?
Dr. Kittai: 17p is still one of our most important prognostic tests. The classic FISH testing that we do is deletion 13q, which is a good prognostic factor, deletion 11q, which used to be a bad one but now seems not to matter as much anymore, trisomy 12, which is intermediate, and deletion 17p.
We knew that patients who had deletion 17p on FISH did not respond well to chemotherapy. Our new agents work for patients with 17p.
In general, we favor continuous therapy for patients with deletion 17p. Not to say that you can’t get time-limited therapy with 17p, but it appears that 17p may matter more with time-limited therapy than it does with continuous therapy.
Typically, 17p goes hand in hand with TP53, which is done on next-generation sequencing. Sometimes they can be discordant. It’s pretty much the same thing.
In the clinical trials, when we talk about these combinations, we’re trying to see if these alternative strategies will be better in higher-risk disease individuals versus non-high-risk disease individuals.
Dr. Nicole Lamanna
Dr. Lamanna: Patients who had these features were considered more adverse or worse, but these new targeted therapies have done great for those individuals.
In the clinical trials, when we talk about these combinations, we’re trying to see if these alternative strategies will be better in higher-risk disease individuals versus non-high-risk disease individuals. How do we tailor our therapies better depending on the features of your disease?
Patients with 17p and TP53 are doing so much better on these targeted therapies. They’re still important but compared to the chemoimmunotherapy days, folks are doing much, much better because of these targeted therapies.
RSV Vaccine
Patient: What is the consensus on the RSV vaccine?
Dr. Wierda: I don’t think there’s a consensus yet. It’s a new vaccine. We heard a little bit of data at the International Workshop on CLL meeting. We need more data on its effectiveness in patients with CLL.
I don’t see a lot of drawbacks in giving it but we haven’t entered an era where we’re recommending it for every patient like we do for the flu shot. That may come, but because it’s a new vaccine and there’s limited data in the general population, there’s not any data available for us in the CLL community.
Even though there are risk-benefit ratios for everything you do in life, including side effects potentially from some vaccines, we don’t want you getting sick and being admitted to the hospital due to these infections.
Dr. Nicole Lamanna
COVID Vaccine
Dr. Lamanna: We think about vaccines because we’re trying to mitigate infectious complications in patients with CLL. In general, for many CLL patients, the immune system is impaired so your ability to mount the same type of antibody response to some vaccines compared to patients without CLL is generally not as good, but that doesn’t mean you shouldn’t get them.
The point is that you can get the flu shot and still get the flu, you can get the COVID vaccine and still get COVID, but if it diminishes the severity of those illnesses and prevents hospitalizations, that’s what we’re trying to do, right? We’re trying to give you any armamentarium that you might have to protect yourself from bacterial or viral infections that are running around so you’re not as sick.
One of the complications we see in CLL patients is infection — pneumonia, sinusitis, cellulitis, and hospitalizations. Infections and recurrent hospitalizations inhibit the quality of life. We have many patients who go through this day in and day out. We try anything we can use to diminish infections.
Vaccines may not be perfect, but we still recommend the COVID vaccine. Despite all the potential side effects, you should get the vaccine. We lived through 2020 and saw how bad it was. We saw how many people died. CLL patients had one of the highest mortality rates due to COVID.
Even though there are risk-benefit ratios for everything you do in life, including side effects potentially from some vaccines, we don’t want you getting sick and being admitted to the hospital due to these infections.
There is no evidence that the COVID vaccine causes CLL.
Dr. Adam Kittai
Jeff: Dr. Kittai, I know the answer to this question, but I need this to be reinforced in our community because it is a pervasive belief. There are a large number of patients who believe the COVID vaccine gave them CLL. Can you talk about why they think this?
Dr. Kittai: There’s no data to state that the COVID vaccine gave patients CLL. Honestly, it comes back to the statement that Dr. Nicole made. A lot of people think that they get the flu vaccine then they get the flu. Ultimately, when COVID was first happening, we were recommending our older patients to get the COVID vaccine.
Given that CLL is a disease of older patients, there’s going to be a chance that any older patient might develop CLL at any given time. It may have also been that someone may not have seen the doctor for a while, got COVID, went to see the doctor, and finally had labs. Remember that CLL is usually diagnosed incidentally so it just might be timing, but there is no evidence that the COVID vaccine causes CLL.
Optimized Care & Limiting Side Effects
Jeff: Dr. Bill, some treatment protocols have side effects. How, when, and what do you communicate to the healthcare team? What information do you need to help mitigate what can be unpleasantness in CLL treatment?
Dr. Wierda: That’s a tough question. All of the treatments that we use have their own set of side effects and toxicities that we see more commonly than others. There are rare things that we don’t commonly see, even if we see a lot of CLL patients on a particular treatment.
Letting your care team know what’s happening, what’s new, what’s uncomfortable and concerning to you is important. Talk to your physician. It’s hard to say if there’s anything in particular because each treatment has its own set of toxicities so we look for different things depending on the treatment that patients are on. But as I mentioned earlier, most of these treatments are very well tolerated by patients and much better tolerated than chemotherapy.
Letting your care team know what’s happening, what’s new, what’s uncomfortable and concerning to you is important.
Dr. William Wierda
Jeff: Watching other people go through it, chemo is not a pleasant experience. When I went through my clinical trial, which was a monoclonal antibody, my first day was not the suggested six hours of a few bumps. It was a full day of unpleasantness. Why is it that so many of these treatment protocols have a bad first day?
Dr. Wierda: What you’re referring to is mostly the CD20 antibodies. What we see is called the first infusion reaction. There is an immune component. You get a monoclonal antibody that binds to your leukemia cells and some chemical messengers are produced in your body. You get a fever and shortness of breath. The higher the white blood cell count, the more severe those reactions tend to be. It’s an immune reaction from the infusion itself that quiets down when the infusion finishes.
Sometimes people have a little bit of fever a day or two after their infusion because there’s not as much leukemia there. For the second infusion, those reactions are much less. We try to pre-medicate patients liberally with steroids to mitigate those, although we can’t always achieve that with steroids. But the subsequent infusions are less severe, usually because there’s less disease.
Jeff: We talked about secondary cancers or associated conditions. Everybody knows you’re supposed to be taking care of your comorbidities. One of the things batted around a lot in the support groups is that CLL patients should be seen by dermatologists regularly. What’s going on there?
Dr. Lamanna: Because your immune system isn’t as good, your body’s ability to surveil and prevent other things from happening is not as good as well. In addition to the infections, this can also play a role in increased risk of other cancers.
All of us are bombarded each day by different environmental stimuli in addition to our genetic components. If you have CLL, your immune system is more impaired so your body’s ability to overcome them is dampened.
There’s no doubt there’s an increased risk of other cancers. Skin cancer is one of the most common we see in CLL patients, mostly basal and squamous, although there could be melanomas as well.
If the dermatologist is following something, they’ll tell you if they want to see you more frequently. Listen to what they say, but at a minimum, see them once a year. If they find something early, they remove it and send it for pathology. We recommend it not just for dermatology but for other routine cancers as well.
Because your immune system isn’t as good, your body’s ability to surveil and prevent other things from happening is not as good as well. In addition to the infections, this can also play a role in increased risk of other cancers.
Dr. Nicole Lamanna
Jeff: When should CLL patients be getting their colonoscopies?
Dr. Lamanna: Unless they have a family history, the age has shifted to 45. It used to be 50. We tell people to get their screening.
The point of a colonoscopy is to try to catch polyps. There is a lag time for most individuals on when polyps could turn into a malignancy. The goal is if they find those polyps, they remove them.
Generally speaking, if you have polyps, they’ll probably tell you to come a little sooner to get a repeat colonoscopy. Rather than 5 to 10 years, they might say 2 to 3 years. If you’re clean, they’ll probably say you’re good to go for 5 to 10 years.
I encourage my patients to do it a little sooner. The guidelines have shifted to 10 years if you’re clean. But if you have polyps, they’re going to want to do it sooner. The goal is to catch polyps early and remove them so that you don’t have a problem.
We recommend age-appropriate guidelines for other cancers. For folks who are much older, there comes a point in time where your utility of screening diminishes unless you’re high risk for a particular reason or you have a lot of polyps.
Some tests look at the DNA in the stool. For patients who have clean colonoscopies and are older or may have issues, doing a colonoscopy might be contraindicated for other reasons. There are other ways to screen people so we encourage you to talk to your docs about those, too.
Jeff: Are there any other conditions that CLL patients should be aware of other than the standard cardiac issues, high blood pressure, and diabetes? What else should we be looking at? Are we more susceptible to something else?
Dr. Kittai: Other things to think about are secondary cancers associated with treatment. For patients who have gotten prior chemoimmunotherapy, specifically with fludarabine or bendamustine, there is a risk of secondary myeloid leukemias that we have to watch out for so that’s why it’s also important not to stop following with your CLL doctor. Even if your counts are all normal and everything’s fine, you should still see a hematologist long-term to monitor for that and that’s going to be a simple blood count.
Other things that are associated with CLL include autoimmune complications. Most often, autoimmune complications coincide with progressive disease so that’s something that we follow. Autoimmune complications include autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). We have to watch out for those as well.
Sometimes you can have complications that may happen down the road and your primary care doctor is not going to know how to manage those so finding a CLL specialist becomes very important.
Dr. Jackie Broadway-Duren
Finding a CLL Specialist
Jeff: Dr. Jackie, we talk a lot about getting a CLL specialist. How do people get a CLL specialist? If you don’t live in a big city, how do you get a CLL specialist?
Dr. Broadway-Duren: You can always go to the LLS site. You can talk with your local oncologist whether they are CLL specialists or not, and they may be able to point you in the right direction or refer you to someone.
There are listings on the Internet where you can look up those things, particularly within certain hospital systems. Many times, patients are sent from the community. You can look it up or contact someone who is a CLL specialist.
Let me reiterate the importance of having a CLL specialist. If you come to Houston, we initiate you on therapy, say you’re doing well and we don’t need to see you as frequently, when you go back to your local areas, you need to have a specialist there, even just an oncologist in some cases.
Sometimes you can have complications that may happen down the road and your primary care doctor is not going to know how to manage those so that becomes very important.
If you don’t understand the disease process, it’s difficult to understand how to manage side effects from treatments. They may not be acute side effects but something that happens down the road. You need someone with the knowledge to manage that.
The problem lies in when you live out of town or out of state and we can’t examine you to make the appropriate choices on how to intervene. You need somebody knowledgeable enough to know how to manage these things.
Jeff: I’d like to shout out to the CLL Society. They have an Ask the Experts program that’s available. If you’re having difficulty finding a CLL specialist in your backyard, it’s a great place to start.
Telemedicine has created opportunities for all of us that didn’t exist before COVID so you should take every advantage that you possibly can to get a CLL specialist on your team.
Work with your care team, your mid-level providers, or the pharmacists to help with patient assistance programs.
Dr. William Wierda
Cost of Treatment
Jeff: Our CLL specialists have talked about new treatments already here and coming down the pipeline. Dr. Wierda, how much do these cost?
Dr. Wierda: The new treatments are very expensive, without question. Most patients with CLL are in the Medicare age category and not all of them have supplemental insurance.
Medicare pays for 80%. Twenty percent doesn’t sound like a lot, but if you’re talking about $10,000, $12,000, $15,000 a month, 20% is a lot of money, particularly for patients on a fixed income.
There are a lot of patient assistance programs. The best recommendation to navigate the whole process is to work with your care team, your mid-level providers, or the pharmacists to help with patient assistance programs and opportunities that we have for patients to get the treatments that they need. There are a lot of them out there.
Mental health is one of the things that we really should focus on, especially for patients with cancer.
Dr. Adam Kittai
Dr. Lamanna: When we’re about to initiate therapy for a patient, we will initiate that process on their behalf. We’ll prescribe and see if their insurance approves the medicine and what their copay is for the drug. We get that response back within a few days. We’ll sit down and talk if we’re going to go forward on a particular treatment based on that information.
If there seems like there’s a hiccup because of a large copay, the pharmacy team lets me know right away and they reach out to the patient to see if they can apply on the patient’s behalf to these assistance programs to see if they can get a reduction in the copay. We don’t start anything until we know and that we’ve all agreed that it’s okay.
Clinical trials are a different beast. This is how our European colleagues get a lot of the drugs they don’t have access to by getting their patients on clinical trials.
There are some patients whose copay is unreasonably high. It doesn’t happen often, but it does happen. We have to decide if that is a blockage to start a particular therapy or not. We have those conversations, but for most people, we do this behind the scenes before we start therapy.
Strategies for Coping & Living Well with CLL
Jeff: Dr. Kittai, how often do you interact with your patients on the mental health aspects of dealing with this disease?
Dr. Kittai: If I’m ever worried about a patient, I do engage. I work with a wonderful team of nurses, nurse practitioners, and a case manager. My case manager has a very bubbly personality. She knows all the things that she can help with. I usually ask her to go and talk to patients after I talk to them.
Mental health is one of the things that we really should focus on, especially for patients with cancer. In addition to telehealth with cancer doctors, telehealth with psychologists and psychiatrists is huge these days.
Be open and honest with your physician about how you’re feeling. Depression causes fatigue. That is one of the main things I screen my patients for when they’re complaining of increased fatigue that is disproportionate to the amount of CLL that they might have.
If you’re actively having depressive symptoms, if you’re struggling, you need to let your doctors know because there are things that we can do.
Jeff: I want to dig a little bit deeper into this because it’s such an important aspect. What is depression?
Sometimes just being able to talk about it is an immense relief so I encourage you to all be candid with your team about mental health.
Jeff Folloder
Dr. Kittai: There are two screening questions I use for my patients. Would you describe yourself as being depressed? Typically, someone who has depression has thought about it. It’s not something that is not without mind.
Have you lost interest in the activities that you typically like to do? If you answer yes to either of those questions, there are more screening questions after. But if you have either of those things, I would seriously consider talking to your doctor.
The worst form of depression is suicidal ideation. I would say that if you have any concerns that you are feeling down and out and it’s related to your cancer diagnosis, there are certain things that we can do. There are programs that we have or have patients see psychologists and psychiatrists to help our patients through this.
Jeff: That’s good information. It’s good advice and good direction. Oftentimes, patients believe that there is a stigma associated with depression. If you are exhibiting any of those symptoms, if you loved playing catch with the dog and that doesn’t do anything for you anymore, let your team know. There are a lot of resources available. Sometimes just being able to talk about it is an immense relief so I encourage you to all be candid with your team about mental health.
To date, we have no supplements that cure CLL that I’m aware of. I’ve read no studies to support that.
Dr. Jackie Broadway-Duren
The Role of Diet & Exercise in the CLL Journey
Jeff: Dr. Jackie, we have three basic groups in our patient support communities. We have patients who take an active role in their care. We have patients who just lay there and take it. Then we have patients who believe that they can diet and exercise their cancer into oblivion.
I worry about my diet and I worry about my exercise, but I’m not doing it to make my cancer go away. I’m doing it because I’m addicted to endorphins and I admit that freely. Let’s talk about diet and exercise. What is the role of diet and exercise in the CLL journey?
Dr. Broadway-Duren: We have patients who think that there are specific dietary supplements they can take that will help cure or treat their CLL. To date, we have no supplements that cure CLL that I’m aware of. I’ve read no studies to support that.
However, we do encourage patients to eat a healthy diet low in saturated fats. You want to eat healthy fats, such as avocado and grapeseed oil. Eating a diet that’s high in fat and carbs makes you tired.
Eat things within reason. I talk to people all the time about exercise and, many times, their response to me is, “If I’m already tired, how can I exercise?” Believe it or not, when you’re tired, just as Jeff said earlier, if you just get up and put one foot in front of the other, if you just walk from down your driveway maybe to the mailbox and back to the house, that’s a form of exercise.
Nobody has to run a marathon or do 50 laps in the pool every day. Anything that gets you moving and gets your heart rate up is going to be beneficial towards helping CLL and your overall body health in general.
Eat healthy. Drink lots of water. Any patient who comes to our clinic knows there’s a constant theme of hydration.
Dr. Jackie Broadway-Duren
As far as supplements, several years ago there were some studies about green tea extract and its benefits, but I don’t know of any patients that were cured of CLL from green tea. I can’t argue against the fact that maybe it may be beneficial, but everything within reason.
When patients are in therapy, I try to tell them to stop all supplements because they’re not regulated. We don’t know exactly what’s in them and the quantity of what’s in them. We don’t know what’s going to interact with the drugs you’re taking for CLL and compete for that pathway where those drugs are metabolized.
Eat healthy. Drink lots of water. Any patient who comes to our clinic knows there’s a constant theme of hydration. They walk in the door telling me how many bottles of water they drank. All of us need to stay hydrated.
For patients who are on the venetoclax ramp-up, we are monitoring tumor lysis. We are monitoring your potassium levels very closely so that’s not the time to take one potassium supplement and think if one is good, three is better. We will tell you to lay off the potassium supplements at certain times during the ramp-up phase.
Disclose to your physician and team other alternative medicines you may be taking.
Dr. Nicole Lamanna
Dr. Lamanna: I want to echo what Dr. Jackie is saying. I don’t want everybody to feel like the docs and the team are against supplements because it always comes off that we don’t believe in any other alternative medicine strategies.
To be fair, part of that may be a fault of the system. It takes funding to run clinical trials with alternative medications. Remember, some plant-based therapies have become cancer therapeutics. It’s not that we don’t believe in other therapies. It’s just that what may work for one cancer may not work for another cancer. When we talk about supplements, we haven’t tested them in the CLL community, outside of the trial of the green tea.
You must disclose to your physician and team other alternative medicines you may be taking. People don’t want to talk about it. Sometimes they feel that the doctors will get upset, but the truth of the matter is that they may have an impact on your organ function, like your liver and kidneys.
Supplements are drugs, too. Anything we take in has to be processed by our body. There may be drug interactions with other medications, even medications that have nothing to do with your CLL. It’s important to disclose anything you might be taking or considering taking so that your team can talk to you about the potential downsides, benefits, and so forth.
It’s not that we don’t believe in them. We want to keep you safe. It’s a conversation that needs to be held.
Everything in moderation. Battling cancer is hard in and of itself. The more that we take away things that we find joy in makes it even harder to battle the cancer.
Dr. Adam Kittai
Jeff: Dr. Wierda, I love a good hamburger. Do CLL patients do better on a plant-based diet versus a meat-based diet?
Dr. Wierda: Not to my knowledge.
I love hamburgers myself, but I don’t eat hamburgers often because they’re not good for you. And I don’t have CLL. There’s a lot of fat in them.
Moderation is my keyword. I love French fries. I love onion rings. You can’t eat that stuff all the time. It’s not good for you.
A lot of it is common sense. There isn’t any diet that’s been shown to be beneficial for patients with CLL in particular.
Jeff: If a CLL patient is in watch and wait or in treatment, are there any vitamins that they should be taking, or should they just be focusing on eating good food?
Dr. Wierda: I take a multivitamin every day. Some things are helpful in terms of the regular multivitamins a day for patients with CLL and non-CLL patients.
Dr. Kittai: My general recommendation is the same. Patients who are healthier when they start treatment do better. If you come in in a healthier state, you’re going to do better. There is no food that we typically recommend.
Once again, it’s everything in moderation. Battling cancer is hard in and of itself. The more that we take away things that we find joy in makes it even harder to battle the cancer.
If you like a hamburger every once in a while, that’s fine. If that makes you happy, that’s fine. It’s not going to affect anything going on with your CLL. It’s a matter of keeping everything in moderation. Make sure that your health is as best as it can be because the healthier you are, the better you tolerate therapy.
Moderation should be the key. It’s not that you can’t have some dietary indiscretions, but it shouldn’t be all the time.
Dr. Nicole Lamanna
Jeff: What about alcohol? I’ve joked around quite a lot about if my doctor ever says I have to give up alcohol, I probably will be getting a new doctor. That’s the way it is.
While we’re talking about stuff that we put in our bodies, I would like for Dr. Lamanna to address what I see thrown out on support forums every single day without fail. Sugar feeds cancer. Why do people persist in saying sugar feeds cancer?
Dr. Lamanna: If you have a lot of sugar in your diet, a lot of carbs, and a lot of other things that are not good for your body, you’re not taking care of your temple, and that leads to other medical problems. People who have diabetes are impaired in terms of healing because of their high sugars. It impairs their immune system and healing ability.
If you take care of your body and your temple, then you’re better able to deal with other medical problems or CLL therapy that goes with the territory because you’re a better fit and your organs function better. There’s a lot online about how high sugar levels are bad for cancer. It’s not just bad for cancer; it’s bad for other medical problems, too.
Moderation should be the key. It’s not that you can’t have some dietary indiscretions, but it shouldn’t be all the time and that’s where that feeds into. I don’t like to take everything away from everybody.
Lowering your sugar and your potential of getting other medical problems are going to be important in how you fight off infections and cancers.
Jeff: Dr. Kittai, is there a connection between CLL and cholesterol levels?
Dr. Kittai: Correct me if I’m wrong, but I have not seen any connection between cholesterol levels and CLL levels. CLL mostly affects older patients. As we get older, we have more difficulty regulating our glucose and our cholesterol, and that just comes with aging and the American diet.
Ultimately, what it comes down to is to take care of yourself and your other comorbidities, and you should do better with therapy. But generally, there’s no link between cholesterol and CLL.
Jeff: Dr. Jackie, we’ve been talking about the fuel that we’re putting in our temple and taking care of the spiritual center of our temple, making sure our mental health is in order. Are there any other tips you want to share? How important is it for CLL patients and their caregivers to take charge of their bodies, take charge of their lives?
Mental well-being is as important and sometimes more important than physical well-being.
Dr. Jackie Broadway-Duren
Dr. Broadway-Duren: It’s very important. We determine how we can cope with things. Sometimes our coping mechanisms are not 100%. You’re weighed down with, “I have CLL. They say I don’t need treatment yet, but that’s in the back of my mind.”
Maybe with the job you had, you’re not able to function fully anymore so you had to cut back on hours and now you have financial responsibilities that you have to worry about. Some people are already at retirement age so if you’re retiring with CLL, you’re not bringing in as much income so you can’t always afford to continue to do the things that you were doing.
If you’re having problems coping and you feel like you’ve just been weighed down, talk to someone. When patients come into the clinic, as Dr. Kittai alluded to, all of them are screened. The nurses screen them with a questionnaire every visit.
If there’s a patient who tells us that they’re having some problems coping or some suicidal ideations — and, yes, sometimes patients do — that’s an immediate call for help. We contact the social worker or psychologists and then psychiatry in some cases to get those patients’ immediate attention.
If you have somebody that you can confide in and talk to that can help allay some of that anxiety and depression, then do that. Speak to a licensed counselor. There are times when patients have to go on antidepressants or anti-anxiety drugs temporarily to get them through that immediate period.
Mental well-being is as important and sometimes more important than physical well-being. Their CLL status doesn’t matter if they’re at a point of wanting to commit suicide. That’s a very key fact that we have to address and do address. I encourage patients to always talk to somebody. If they don’t talk to you about it, then find someone who they can.
Jeff: Excellent advice.
Our relationship with our spouse and a healthy sex life is very important.
Dr. William Wierda
CLL & Sex Life
Jeff: Dr. Wierda, you’re part of CLL Global. I would be remiss if I did not channel a part of CLL Global’s founder, Dr. Keating. Since you are here in his stead right now, you know that one of his big action items is his patient’s mental health.
Part of that is how they’re getting along with their significant other so I’m going to quote him. Let’s talk about sex. How important is a CLL patient’s sex life? How do we deal with it?
Dr. Wierda: It’s important for everyone. Something that you said in the very beginning resonated with me and that was that you have taken account of your priorities in life — who’s important to you and building relationships with those who are important to you. That’s a special thing and not everybody does that.
You don’t have to have CLL to do that. COVID helped with that a little bit, but perhaps we should take your advice on that and take account of what’s important to us.
Our relationship with our spouse and a healthy sex life is very important. We’re all human beings and although I blush about it, it’s just part of being a human being.
Jeff: It’s part of being a normal human being. If that part of your life is no longer normal for whatever reason, get some help. That’s what we’re talking about here. If something’s not working the way you want it to, get some help.
I ask the patient how they would like to bring other people into the conversation and who they want to share this information with, and then we work on that depending on each patient.
Dr. Nicole Lamanna
Talking to Family & Friends About CLL
Jeff: How do we talk to family and friends about our CLL diagnosis? There are a million and one different approaches and strategies, and people believe one way is better than the other. What are some strategies for this?
Dr. Lamanna: First is the comfort level. Each patient is different. Some people have to get a handle on the diagnosis themselves first. Usually, when I have that conversation, I ask who they want to include in the conversation. Sometimes they’re ready to do that, sometimes they’re not and need a little time.
You can’t remember everything in one sitting. Oftentimes, I say, “Why don’t you bring your family member, your significant other, children if you want to?” If you can’t explain it, you can’t relay everything about your new diagnosis when you’re hearing half of it most of the time.
Oftentimes, I’ll suggest calling them on the phone or bringing them to the next consultation so I can explain things and if they have questions.
I ask the patient how they would like to bring other people into the conversation and who they want to share this information with, and then we work on that depending on each patient.
Depending on how old you are, that conversation can be tailored differently because some people feel they’re not ready to share with their extended family, their children, or people at work. People have different times when they feel comfortable and ready to include others. I do think that’s personal and different for everybody.
I encourage all my patients to let their kids know when they get this diagnosis because, ultimately, it’s important for them to know.
Dr. Adam Kittai
When it comes to children, there are adult children and there are little children. When they’re little children, there are support groups that we can reach out to on the patient’s behalf, like CanCare. Different groups can incorporate how to do that with children.
Children don’t need to hear everything, but they are savvy. Even little children are savvy. They’ll get very upset not knowing because they do know something’s going on. They’ll be more upset about the fact that they don’t feel like they’re included. If they have little children, I encourage the patient by finding a forum to do this because I think it’s important for the child.
Dr. Kittai: As an older child with aging parents, one of the things that I’ve talked to my parents about was the concept of protecting me. I don’t know if everyone’s a little different, but trust me — you’re no longer protecting your kids from this diagnosis. You want your family to know what you’re going through.
At the end of the day, it’s your children who are going to be the ones helping you through all of this. It’s important to let them know if something’s going on as soon as possible, in my opinion.
This is something very personal to me. I encourage all my patients to let their kids know when they get this diagnosis because, ultimately, it’s important for them to know, they need to help if they can, and be supportive of you going through this process. The whole concept of protection because they’re better off not knowing, I think, is a total fallacy.
It also depends on the family dynamics… You have to look at the family dynamics and what type of relationship they have with family members.
Dr. Jackie Broadway-Duren
Dr. Lamanna: There’s more hurt involved that way. Would you tell them that you didn’t have heart disease or diabetes? It’s the same concept. Most people know they’re taking medicines.
Your children want to know what’s going on with you. If they can be supportive, great. They may be supportive in ways that you never even could have imagined. I think it’s important early on.
Everybody does need a little bit of time to digest their diagnosis first, which I get, but I think it’s important to include others.
Dr. Broadway-Duren: It also depends on the family dynamics because, in some families, they’re not in that type of relationship to share with certain family members. When you talk to a patient over time, you get a sense of what the family dynamics are.
If it’s going to be more of a stressor for them to share this with their kids who may not be as supportive, then maybe they shouldn’t. It’s individualized. You have to look at the family dynamics and what type of relationship they have with family members.
I have a patient I’ll never forget. He and his wife thought they were doing the right thing for many years and didn’t tell their kids from when they were small until they graduated from high school. When they finally told them, they were very angry for a long time. I always encourage patients to talk to their kids and be honest with them, if they can.
When you get a CLL diagnosis, you have a unique opportunity in your life… CLL allows you to stop, figure it out, and take care of what’s important.
Jeff Folloder
Jeff: Everyone has a different family dynamic, but for the most part, we have family members who deeply care about us and are deeply concerned about what’s going on. They may not always be able to express it well and you may not always be able to understand how they’re trying to express it.
My mother passed away shortly after I was diagnosed with CLL. She was dealing with Parkinson’s at the time. I have the very last voicemail she ever sent me. Whenever I need a little bit of centering and focus, I play that voicemail back.
She says, “Hello, Jeff, it’s your mother.” You could tell that her voice was creaky and that she was under duress and strain. “I need you to call me back. I need an update on your health situation. Love you. Bye.” I can’t get rid of that voicemail. That tells me that my family is important to me.
My youngest daughter asked me to serve as a mentor in her school and I’m happy to provide that service. When she has problems, she comes to me. I owe her the respect of letting her know what’s going on in my world and what I need from her. I do that with her sister and with her mother.
When you get a CLL diagnosis, you have a unique opportunity in your life. You can pull up the parking brake instantaneously and decide what it is that’s going to be important to you going forward. You can make the personal decision to get rid of the stuff that doesn’t matter. You have to determine if the juice is worth the squeeze. A lot of times, it’s not. CLL allows you to stop, figure it out, and take care of what’s important.
If you find that you have to take NSAIDs multiple times a day for multiple days in a row, that’s something that you really should let your doctor know about.
Dr. Adam Kittai
Q&A
NSAIDs for Joint Pain
Patient: Being on ibrutinib, I can’t take ibuprofen or naproxen. Tylenol is great but not strong enough for a lot of muscle-skeletal pain and I’m wondering if you have any recommendations.
Dr. Kittai: You can take naproxen and ibuprofen but not all the time. If you’re having severe pain, it’s okay to take an NSAID every once in a while, but it can increase the risk of bleeding and it can affect your kidneys. We don’t want patients on it long-term. We use a calcium-magnesium-phosphate supplement. It’s a triple pill that can help with joint pain associated with ibrutinib so you can ask your doctor about it.
If you’re having long-term pain, you should also be evaluated, too. I often send my patients to ortho. In addition, if we think the joint pain cause is ibrutinib, I switch to second-generation BTK inhibitors. You can dose reduce or do dose holds as well if the joint pain is directly related to BTK inhibitors.
The classic naproxen dosing is five days. I wouldn’t take it longer than that. If you find that you have to take NSAIDs multiple times a day for multiple days in a row, that’s something that you really should let your doctor know about.
Dr. Broadway-Duren: As far as joint pains, topical Voltaren gel has been shown to show benefits in patients. It’s over-the-counter. I’ve heard some positive outcomes with using that topical gel.
Jeff: Joint pain is a very common complaint in support groups. A lot of people report that taking Claritin helps with joint pain. What’s going on with that? I’ve never made the connection.
Dr. Lamanna: Antihistamines in general can help with the inflammatory response in your body. Even people who take vaccines and have reactions to vaccines take that, too, because it might mitigate some of the autoimmune inflammatory response.
Dampening this very hypersensitive immune drive that you have from CLL where you get exaggerated responses to certain medications, bug bites, and other things can be driven down sometimes with the antihistamines.
If you’re trying to stay healthier, it’s about maintaining your diet, not eating excessively, and not doing things excessively. The key is everything in moderation.
Dr. Adam Kittai
Dr. Kittai: We’ve given short courses of steroids as well.
Dr. Lamanna: Figuring out if this is related to the drug or arthritis will help the doctors figure out how to best help you with certain supportive medicines or other referrals.
Dr. Kittai: Don’t be afraid if you get steroids and your white count jumps up; that’s a normal reaction. Every single time you get a steroid injection within a week of seeing your doctor, your white count will go through the roof. It’s a normal effect so don’t be worried. It will come down again.
Intermittent Fasting
Patient: Intermittent fasting is a big trend. Several of my family members do it and my son said, “If you fast long enough, your body starts to generate stem cells.” Could that be any help with our CLL?
Dr. Kittai: Not that I’m aware of. At the end of the day, diet and exercise are the key. Oftentimes, it’s hard to stick with a diet so I tell my patients to choose a diet that works for them.
Most diets are good because they limit caloric intake. If you’re trying to stay healthier, it’s about maintaining your diet, not eating excessively, and not doing things excessively. The key is everything in moderation.
Dr. Lamanna: If you’re fasting, make sure it’s okay with your other physicians in case you’re on medicines where you shouldn’t be fasting.
There probably is some genetic basis because there are multiple family members affected, but we just haven’t figured that out yet.
Dr. William Wierda
Familial CLL
Jeff: I have CLL. My uncle has CLL as well. Is CLL hereditary?
Dr. Wierda: There’s familial CLL where multiple family members have a diagnosis of CLL. It’s usually family members who are directly related like mothers, fathers, uncles, aunts, brothers, and sisters. Multiple family members are affected.
While 10% of patients with CLL have familial CLL, 90% are sporadic, meaning there’s not any family association with a diagnosis.
For a while, we’ve been interested in understanding the risk factors for familial CLL. What’s the genetics behind why family members develop CLL? We haven’t figured that out yet, but we’re interested in it. There probably is some genetic basis because there are multiple family members affected, but we just haven’t figured that out yet.
Jeff: Is there any group of people or ethnicity that may be more prone to this?
Dr. Wierda: There’s a high incidence of CLL among individuals of northern European descent. It’s very uncommon in the Japanese population. Those with an Ashkenazi Jew heritage also are at increased risk.
Dr. Lamanna: Sometimes, CLL may not be part of the familial CLL incidence, but there might be a more global issue in the family genetics, meaning a predisposition to cancers in general so CLL could be one of them.
When we first see patients, we often ask them about their family history to see whether or not they should be screened for familial mutations that might run in the family that might warrant genetic screening for other cancers.
Patients who have good disease control on BTK inhibitors can go without therapy for around 2 to 3 years.
Dr. Adam Kittai
Dosing of BTK Inhibitors
Jeff: Dr. Kittai, the idea of reducing dosage or stopping the dosage for a BTK inhibitor. How does that work? What patients are candidates?
Dr. Kittai: I don’t know if everyone shares this opinion but now that we have the second-generation BTK inhibitors, which are safer than ibrutinib, I favor the second-generation BTK inhibitors when I’m starting patients on BTK inhibitors.
A lot of people who are on ibrutinib are asking if they should switch to the newer class of BTK inhibitors that are safer. I don’t typically switch if someone’s tolerating ibrutinib very well.
If someone has been dose-reduced on ibrutinib or if they’re developing symptoms due to ibrutinib, I switch. I have a low-threshold switch. I don’t mess with dose reductions anymore. I switch patients to second-generation BTK inhibitors.
In terms of dose reductions on second-generation BTK inhibitors, it depends. If I’m starting therapy, usually within the first year, I try to maintain the dose as best I can and treat side effects that might be associated with the drug.
In general, we can reduce the dose. I try not to do it in the first year but that depends because I’m trying my best to get as good disease control as I can. That’s an overall sense, but there are exclusions to that. Talk to your provider about when a dose reduction is appropriate.
Another question is if a patient on BTK inhibitors for several years can stop. I’ve done this in one patient who had undetectable minimal residual disease. She was fed up with taking her BTK inhibitor. She’s still doing well. We now have some data that shows that that is something that maybe we should be considering.
We know that patients who have good disease control on BTK inhibitors can go without therapy for around 2 to 3 years. I also have had patients that buck that trend as well. These numbers are not absolutes. These are all averages and medians so some people may not have 2 to 3 years and some people have much longer.
There was data presented at iwCLL where they stopped patients’ ibrutinib who had good disease control and measured the amount of disease that came back over time. Most of those patients one year out of stopping had stable disease.
This is something that’s coming. In select cases, I would consider it as I have done but talk to your physician about that if that’s something that’s right for you.
In general, if you’re healthy and you’ve been vaccinated, you can’t go through life being worried about every little thing every minute. Use caution.
Dr. Jackie Broadway-Duren
Exposure to Infections
Jeff: Dr. Broadway, a patient asks, “I’m afraid to go to restaurants and other crowded places. Should I be worried?”
Dr. Broadway-Duren: I am.
Here’s the deal. For patients who are on therapy and maybe neutropenic, meaning your absolute neutrophil count is low, less than 1.0, then yes, you should have some concern about being out and about eating at restaurants and so forth.
I try to not recommend or even discourage patients from going to these all-you-can-eat buffets. Pay attention to what people are doing before they reach for those ladles. I strongly discourage them from eating at buffets, as I don’t myself routinely.
If you’re neutropenic, you may want to limit your outings. That would probably be a time to pick up something and eat at home or avoid being around a crowd of people anyway.
In general, if you’re healthy and you’ve been vaccinated, you can’t go through life being worried about every little thing every minute. Use caution. Avoid areas where people are sick. Avoid being in direct contact with them, but use good handwashing and a lot of common sense.
Richter’s transformation is extremely uncommon among patients with CLL who haven’t had treatment
Dr. William Wierda
Richter’s Transformation
Jeff: Dr. Lamanna, are there warning signs for Richter’s transformation?
Dr. Lamanna: Richter’s transformation is transformed from your CLL cells. Sometimes they can change into a more aggressive lymphoma. The most common happens to be what they call diffuse large B-cell lymphoma, but some other transformations can occur such as Hodgkin’s disease and prolymphocytic leukemia.
Back in the day of chemoimmunotherapy, patients presented a lot sicker in general. They would have fevers and chills, loss of weight, and feeling very unwell. That still can happen, but with the targeted therapy, sometimes the transformation can also be more subtle.
Not everybody is very ill when they present. Maybe it’s profound fatigue that seems out of proportion to the rest of how they feel. They might be currently on a drug, but they’re having profound fatigue. If we haven’t found another reason, that would be a reason for us to look.
Sometimes people still get fevers, sometimes their LDH is rising. The presentation is not as classic in my experience.
There’s more of a mix in presentation than when we only had chemoimmunotherapy and patients were much sicker. We still have some patients who present very sick, but there’s a range in how they present.
Most of the CLL community is working on collaborating and trying to develop new and more effective treatments for Richter’s transformation.
Dr. William Wierda
Dr. Wierda: Richter’s transformation is extremely uncommon among patients with CLL who haven’t had treatment. That situation is probably another disease and not something that has arisen from the CLL. We can cure those patients of their Richter’s transformation typically with chemotherapy.
Most of the time, Richter’s happens in patients who’ve had treatment and it’s from the malignant cells and the aggressive cells that have arisen from the original CLL. In those cases, they’re a lot more resistant to treatments and more difficult to manage.
It’s an area of unmet clinical need for us and an area of active research. Most of the CLL community is working on collaborating and trying to develop new and more effective treatments for Richter’s transformation.
Quality of Life of People in Watch & Wait Who Don’t Need Treatment
Jeff: Some patients get diagnosed with CLL, they’re on watch and wait, and then they go on to treatment. Some patients will never need treatment. What percentage of the population is that and what’s their quality of life?
Dr. Wierda: I think it’s exceedingly good. They still can have infections. They still can have other cancers more commonly than the general population. But in general, the disease isn’t growing. It’s not causing any problems. They’re not getting anemia. Their platelet counts are normal and they live a relatively normal lifespan.
In my experience, probably overall it’s 20%.
Jeff: Interesting. I would have thought it would be closer to 100%. I’m surprised to hear 20% don’t need treatment. I would have thought that most CLL patients at some point would need treatment.
Our patients with CLL are living very close to the normal life expectancy, even if they require treatment with our new therapies, which is great news.
Dr. Adam Kittai
Dr. Lamanna: But the counter, I think, is often the way it’s described. Since most people are diagnosed incidentally by their primary care physician or if they’re getting screening for surgery or mammography, they’re picked up routinely. The docs will often go, “Ah, you have CLL, it’s okay. You’re going to die of something else.”
The fact is that the majority of patients do need therapy for their CLL. It’s not the benign disease that everybody talks about when you hear from other doctors not to worry about it. It’s a small percentage of patients who don’t need treatment; the majority do.
One of the first things I do when I see somebody with a new diagnosis is counseling them that 20% likely don’t need treatment, but the majority at some point do. I’d rather you think that you might be one of those. We can talk about the ones that we think are in that 20% group, but that doesn’t mean we have a perfect test that identifies them. Even if you’re a good risk, I wish I could say that they never need treatment but that’s not the case.
Dr. Kittai: To add to that, one of the questions I hear is the average age of death of CLL patients. There was an interesting study that was presented at iwCLL that looked at all patients who were treated in modern-day clinical trials. These are patients who require treatment. They did a study where they took all those patients and matched them to age-matched controls in the general population. The overall survival of the two groups was practically equal.
With treatment, patients were getting very, very close to their life expectancy. Remember, these are all clinical trials so it’s going to seem a little bit low. It was 52 to 55 months versus age-matched controls which was 56 months. Once again, it was age-matched controls so they matched the population to age-matched controls to general society and the difference was only by a few months. That tells us that our patients with CLL are living very close to the normal life expectancy, even if they require treatment with our new therapies, which is great news.
I’ve seen a patient go into spontaneous remission. My point is to be hopeful.
Dr. Adam Kittai
Dr. Wierda: Again, you have to factor in the age component to that. For patients over 65 or 70, we’re achieving probably a similar survival as the non-affected, age-matched controls in the population. This group tends to see younger patients because we’re at academic centers and referral centers so we see young patients.
I have a 17-year-old with CLL who I’m treating now. For that patient, even though we have great treatments, we need a curative treatment, perhaps a stem cell transplant. The life expectancy for a 17-year-old is going to be different compared to an 80-year-old so you have to consider that also.
Jeff: That’s an astonishing bit of information. I had never heard of a CLL patient that young.
Dr. Kittai: One more astonishing thing I’ve seen is someone going into remission without any treatment. I’ve seen a patient go into spontaneous remission. My point is to be hopeful.
Patient: Dr. Wierda mentioned stem cell transplants and I was wondering what work is being done in that area.
Dr. Wierda: Not a lot because we’re not using it as much as we used to. In the last two years, I’ve probably sent two patients for stem cell transplants. Thankfully, we’re not having to utilize it as often as we used to when we were using chemotherapy.
We’re much more enthusiastic and interested in CAR Ts. There is research work with cord blood-derived CAR NK cells. Those are cell-based strategies that may ultimately take over the allogeneic stem cell transplant where you’ve got a donor that you’re doing a transplant with.
We are now in an era where we take a pill a day to keep our cancer away. We couldn’t have said that 10 years ago.
Dr. Adam Kittai
Final Takeaways
Jeff: We have covered a ton of information. This has been great. I love having these sessions. They fill me with hope. It helps me get my message that you absolutely could live a great life with CLL.
What’s one message you want them to hear loud and clear that you could not say a decade ago?
Dr. Wierda: A cure is soon to come. We couldn’t have said that 10 years ago. I remember going to a meeting with a CLL research group that we were collaborating with. Somebody brought up the word cure and one of my colleagues said, “How can you say that? We’re nowhere near a cure. That’s not something we even need to talk about.”
I thought about it at the time and reflected on it. It was before we had ibrutinib or venetoclax. That comment today would not at all resonate with anybody because I do think we have the tools to cure patients with CLL.
A cure is on the near-term horizon for us. We just need to figure out how to use the drugs that we have available now and optimize them to cure patients.
The issues of Richter’s should subside and go away. The issues of refractory disease should go away. Ultimately, and hopefully in the distant or not-too-distant future, the stress and concern about watch and wait will go away because we’ll be talking about curing patients with well-tolerated treatment, and watch and wait will be a thing of the past.
The good news is that from where we came from with chemoimmunotherapy… There’s a lot to be hopeful for.
Dr. Nicole Lamanna
Dr. Lamanna: Targeted therapies have transformed the way we care for patients. We need to figure out ways to tweak the therapies. We have a whole bunch of new players coming in the mix and that will impact many patients who have relapsed on BTKs and venetoclax.
There’s a lot of hope for the relapsed population as well. There’s a lot of work that needs to be done. Despite these therapies, we have to figure out ways to improve people’s immune systems. There are still a lot of side effects and infectious complications that we need to work on.
It’s different from when I started. The good news is that from where we came from with chemoimmunotherapy, the side effects, the issues we used to see, and the limitations, there’s going to be a lot more personalization of some of these medications with different subgroups of characteristics of patients within CLL. There’s a lot to be hopeful for.
Think about your blood pressure, your weight, your diet, and all of these things that you need to maintain a healthy lifestyle. Continue to thrive in every aspect of your life.
Dr. Jackie Broadway-Duren
Dr. Kittai: At the end of the day, we are now in an era where we take a pill a day to keep our cancer away. We couldn’t have said that 10 years ago. Not only are these pills effective, but they’re getting safer and safer and safer and that is a really exciting thing for our patients with CLL.
Dr. Broadway-Duren: I want to focus on the patients who are in the watch-and-win category. I want you to think of the analogy of an elephant in the circus. The elephant is the center of all the animals and they’re the largest animal. But other smaller animals around the elephant need to be taken care of.
Think about your blood pressure, your weight, your diet, and all of these things that you need to maintain a healthy lifestyle. Continue to thrive in every aspect of your life so that you’re not so consumed with feeding the large animal, the elephant. All of the animals need to be fed and cared for.
With that being said, I 100% concur with everything that’s been said. I’m excited about the future of CLL and can’t wait to see what’s next.
A cure is on the near-term horizon for us. We just need to figure out how to use the drugs that we have available now and optimize them to cure patients.
Dr. William Wierda
Conclusion
Jeff: I want to thank each of you. Thank you to our doctors.
Everyone in the CLL universe needs to know that progress is being made. I’m hopeful that we are making progress and that the future is indeed bright.
I would like to thank the CLL Global Research Foundation for putting effort and resources in the pipeline to find a cure.
I’d like to thank MD Anderson for taking great care to make sure we have a venue to witness these things.
I’d like to thank The Leukemia & Lymphoma Society for being another shoulder to lean on. Light The Night. Let those balloons go. Make sure everybody knows that we’re going to kick leukemia’s butt.
The Leukemia & Lymphoma Society does an awesome job of education and patient support. They provide so many resources that most of us are unaware of all the good that they can do.
I am constantly referring patients and caregivers to their patient support programs. They’ll help you with your copays, your transportation, and a myriad of things. They print out brochures and information so that you can have a handy guide when you want to figure out what questions to ask and how to get through particular things.
I thank them for their support during my journey and I hope that you’re utilizing LLS as part of your resource package.
I’d like to thank the CLL Society. Dr. Kaufman is providing wonderful resources all across the globe for anyone who asks. These are great people.
I also want to give a big thank you to a local organization in Houston, CanCare. Most cancer support organizations provide help and group support. CanCare approaches things completely differently.
When you call CanCare, you’re interviewed and matched with someone who’s just like you. Whether you’re a cancer patient or a caregiver for a cancer patient, you’re matched with someone and you get to walk that journey with someone who’s been there.
I’ve been a CanCare volunteer for quite some time. It’s incredibly rewarding to talk to someone who’s been recently diagnosed and explain to that person, “We’ll get through this. We’ll figure out a way to get this done.” It’s a unique approach.
They’re a nonprofit that exists exclusively upon the kindness of strangers. For 33 years, they’ve been providing this wonderful support in Houston and other communities across the country. I appreciate the fact that they’re here today.
I’d like to thank CanCare for providing shoulders to lean on and for anyone who needs to get matched.
I would also like to thank our sponsors, AbbVie and BeiGene. When companies like AbbVie and BeiGene sponsor events like this, they do it with absolutely zero editorial control. They know that these types of interactions are not just important for the CLL community, they are crucial for the CLL community. They want the word to get out.
Interested in myelofibrosis clinical trials? We’ve gathered the leading experts to explain emerging clinical trials, misconceptions, and how to find the treatment best for you.
Gain invaluable insights into upcoming exciting clinical trials, the purpose and benefit of trials, and navigating trials and treatments. Optimize communication with your healthcare team and empower yourself with extra support and resources.
Thank you to GSK for its support of our patient education program! The Patient Story retains full editorial control over all content.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
We try to help patients and their supporters navigate a diagnosis and we do this through in-depth conversations with patients, care partners, and top specialists across different cancers.
It’s important to have these educational programs, especially when it comes to topics like clinical trials, which are daunting and overwhelming, so we’re trying to humanize your options.
We’re so proud to be co-hosting this with The Leukemia & Lymphoma Society, the world’s largest non-profit health organization dedicated to funding blood cancer research as well as offering patient services and education.
They have great resources, including information specialists who are a phone call away to help answer your questions. We’ll be highlighting the Clinical Trial Support Center, a very critical free resource that offers one-on-one support to enroll in and stay in clinical trials.
We also want to say special thanks to GSK for supporting our educational program, which helps us make this available and free for our audience. The Leukemia & Lymphoma Society and The Patient Story retain full editorial control of the entire program.
This is not meant to be a substitute for medical advice. We want you to walk away and be able to ask your own doctors and medical teams questions about clinical trials in myelofibrosis.
I know how fortunate I am as many people suffer so much more than I ever have.
Ruth Fein Revell
Ruth Fein Revell, Patient Advocate
Stephanie: I’m thrilled to introduce someone who’s not only a big MPN and myelofibrosis patient voice and leader in the community but also someone I’m lucky to call a friend and who will be leading the conversation.
Ruth, I know that you’re going to share more about your own myelofibrosis cancer story and how you became a passionate advocate. But first, can you share more about yourself outside the cancer context? Because as we know, we are so much more than a diagnosis.
Ruth Fein Revell: Thanks so much, Stephanie. Professionally, I’m a health and science writer who now writes primarily about cancers, blood cancers in particular. I also host patient programs. I have the privilege of speaking to many of the world’s most prominent researchers and clinicians.
In many ways, I think cancer has attracted many of us because we feel we can make a real difference in a difficult disease.
He’s globally recognized as a leader in the MPN space and we are so fortunate to have him with us. Our audience would love to know you beyond that white coat of yours. What drew you to work in cancer and research?
Dr. Ruben Mesa: Cancer is such a terrible disease. It impacts and steals from an individual’s length of life and quality of life. I myself have been touched by cancer as so many have. My father passed from cancer and my mother is a cancer survivor. I was able to witness the impact of cancer research, developing new therapies, and the value of really compassionate care and how important these things were.
In many ways, I think cancer has attracted many of us because we feel we can make a real difference in a difficult disease. It’s also an exciting time when scientific progress is really making a genuine impact.
There are many aspects of myeloproliferative neoplasm that I find extremely rewarding to take part in.
Dr. Angela Fleischman
Dr. Angela Fleischman, Hematologist-Oncologist
Ruth: Dr. Angela Fleischman is a hematologist-oncologist at UC Irvine Health, where she leads the Fleishman Lab with a special focus on MPNs and improving the options and care for patients.
As a physician-scientist, Dr. Fleischman not only treats patients but also actively researches hematological malignancies. She’s passionate about translating findings from the lab bench to the patient’s bedside.
Dr. Fleischman, we’d love to know a little more about your passions as well. What drew you to blood cancers and research?
Dr. Angela Fleischman: I have always been extremely interested in blood cell development. I started out as a Ph.D. student prior to my MD and focused on normal blood cell development and what determines whether a blood stem cell goes one direction or the other.
When I decided to go to medical school and first learned about myeloproliferative neoplasms, I was extremely fascinated by them because I felt that it was an opportunity to learn what happens when blood cell development goes awry.
Another extremely interesting aspect of myeloproliferative neoplasm that I was extremely drawn to is the ability to make connections with patients throughout the years because it’s a chronic disease. As a physician, I’m able to travel with them through their journey as a patient. There are many aspects of myeloproliferative neoplasm that I find extremely rewarding to take part in.
I help patients navigate the complicated clinical trial landscape, and provide them with education and potential treatment options to take back to their care team.
Melissa Melendez: I’ve been in the oncology field for almost 20 years and it was a happy accident how it happened. While in nursing school, I started my first clinical rotation in the oncology unit. I was pretty apprehensive and concerned that I was being plunged into caring for such complex patients with extreme highs and extreme lows of treatment outcomes.
I instantly fell in love with not only helping patients on their journeys throughout their treatment but also the privilege of caring for their families who were going through the journey as well. I decided that oncology was going to be my career path.
I started as a patient care assistant then a registered nurse, a division supervisor, and currently a nurse practitioner. Working for The Leukemia & Lymphoma Society in the Clinical Trial Support Center has been such a blessing for me as a nurse and it was a pretty easy transition from my previous occupation.
I help patients with clinical trials and throughout their journey. Not only do I work with intelligent, caring, and selfless colleagues but also with a population of patients and families that I truly love.
On a daily basis, I get to see the impact that the LLS has on patients and families, help patients navigate the complicated clinical trial landscape, and provide them with education and potential treatment options to take back to their care team to discuss so they can make informed decisions about their care. I get to build relationships with patients and family members that last for years.
It wasn’t until I was taken off hydroxyurea before starting a clinical trial that I realized how severe my symptoms were without treatment.
Ruth Fein Revell
Ruth’s MPN Story
Ruth: What is myelofibrosis? Myelofibrosis is one of the MPNs, a myeloproliferative neoplasm, and a very personal topic for me. I’ve lived with an MPN for nearly 30 years, originally diagnosed with essential thrombocythemia or ET at age 38 while I was raising two young boys.
I was taking an aspirin a day, which was stopped because I developed an ulcer. I ended up with clots in my portal and splenic veins. After a week in the hospital, I was put on an anticoagulant or a blood thinner. Several years later, my bone marrow flipped a proverbial switch and instead of producing too many platelets, it now produced too many red blood cells.
The diagnosis was changed to polycythemia vera and I lived with periodic phlebotomies and daily hydroxyurea. That was part of my life, as with many people who live with polycythemia vera and the different MPNs.
In 2018, I had surgery for early colon cancer. The surgeon was so focused on avoiding any more clots that I had the opposite happen. A major bleeding episode put me in the ICU for nearly a week, followed by several months of healing.
I finally sought out an MPN specialist and began to see Dr. Ellen Ritchie at Weill Cornell in New York. I had an updated bone marrow biopsy, which confirmed a diagnosis of myelofibrosis.
I used to say I was mostly asymptomatic but I’ve lived with severe migraines, a few TIAs (transient ischemic attacks), and other constitutional symptoms my whole life. It wasn’t until I was taken off hydroxyurea before starting a clinical trial that I realized how severe my symptoms were without treatment.
I experienced both life-threatening clots and bleeding episodes. I had such extreme fatigue that I couldn’t walk up the street without stopping to lean or sit on a neighbor’s step. Of course, I also know how fortunate I am as many people suffer so much more than I ever have.
Fibrosis does not always equal the MPN myelofibrosis.
Dr. Angela Fleischman
What is Myelofibrosis?
Ruth: Let’s dig right in. Dr. Fleischman, what exactly is myelofibrosis?
Dr. Fleischman: People may interpret the word myelofibrosis as having some fibrosis in the bone marrow. What we’re talking about is the myeloproliferative neoplasm myelofibrosis, which also can have some fibrosis in the bone marrow. However, I want to emphasize that fibrosis in the bone marrow does not always equal myelofibrosis.
MPN myelofibrosis is a chronic blood cancer that stems from the proliferation of some abnormal mutant cells in the bone marrow. Exactly what causes the fibrosis is unclear. The abnormal megakaryocytes or the cells that are producing platelets have been implicated as the bad cells in myelofibrosis and causing the fibrosis.
Patients also tend to have an enlarged spleen, which can also be seen in ET and PV but is more prevalent in myelofibrosis.
Blood counts can look very different. There’s a wide variety of what a myelofibrosis patient’s blood counts look like, but a classic myelofibrosis patient may have some anemia. They may have a little bit of a high white blood cell count. They may also have immature cells in their blood so their bone marrow cells are not maturing fully before going into the blood, indicating that there’s some stress going on in the bone marrow.
Myelofibrosis patients can have some significant constitutional symptoms. ET and PV can also, but in myelofibrosis, they tend to be more severe.
I do want to emphasize that because somebody has a bone marrow biopsy that says fibrosis does not necessarily always equal the MPN myelofibrosis. Other things, like autoimmune diseases, can cause some fibrosis in the marrow. Infections can cause fibrosis in the marrow. Other blood cancers can cause fibrosis in the marrow. What I want to emphasize is fibrosis does not always equal the MPN myelofibrosis.
Ruth: That’s a really good reminder and not something that people focus on much so thank you for that.
We’ve seen an explosion in many different types of therapies. Over the last three years, we’ve seen a rapid increase in FDA-approved options.
Dr. Ruben Mesa
Advances in Myelofibrosis Treatments
Ruth: The world of MPNs, in particular myelofibrosis, is changing before our eyes as clinicians, researchers, and people living with these conditions. Dr. Mesa, would you tell us how the landscape of treatments for MF patients has changed so dramatically in the last 2 to 3 years?
Dr. Mesa: I first saw patients with myelofibrosis at the beginning of my training almost 30 years ago. In the first half of those 30 years, the medicines we had for myelofibrosis were really limited because we had a very limited understanding of the biology of the disease.
What happened about 15 years ago is we identified important genetic changes, such as JAK2, CALR (calreticulin), MPL, and others that lead downstream to a patient having a myeloproliferative neoplasm.
With that, we’ve seen an explosion in many different types of therapies. Over the last three years, we’ve seen a rapid increase in FDA-approved options, now four different JAK2 inhibitors. They’ve made a real impact in patients with myelofibrosis regarding the enlargement of the spleen, perhaps helping to slow down the course of the disease to some degree and, for some individuals, dramatically so.
The next step we’re launching into is combinations of therapies where we use more than one drug and look at treating different aspects of the disease or different targets in terms of the biology of the disease to make a deeper impact.
Wearing my cancer center hat, as I look at how therapies are advancing in many different diseases, both blood cancers as well as non-blood cancers, most of the time we’re now using more than one therapy where medicines complement each other.
Different blood diseases, such as multiple myeloma, use up to four different drugs at a time. The explosion went from really very little understanding to multiple drugs, a much greater understanding of the biology of the disease, and hopefully a deeper and deeper impact.
For the majority of individuals, probably over 90%, based on a variety of factors, we start with medicines.
Dr. Ruben Mesa
Standard of Care: First-Line Treatment
Ruth: Dr. Mesa, what is the standard first-line treatment for myelofibrosis?
Dr. Mesa: When patients come in with a diagnosis of myelofibrosis, their doctor first gets a sense of the risk of the disease, how likely is the disease to be life-threatening, and the burden that the patient is facing from an enlarged spleen, from symptoms, or from the risk of progression.
We discuss whether we should pursue the potentially curative option of bone marrow transplant or stem cell transplant; we use those terms interchangeably. That’s a very complex therapy, but it’s something that we consider throughout for individuals up until their 70s, depending on the risk of the disease and other factors.
For the majority of individuals, probably over 90%, based on a variety of factors, we start with medicines. The only approved medicines for myelofibrosis are the JAK inhibitors. Transplant either in the near future, delayed, or we’re not going to pursue transplant and then consideration of a JAK inhibitor.
JAK inhibitors help to decrease the activation of JAK2. Regardless of which mutation a patient has or even if they don’t have one of the three mutations, they all seem to benefit from JAK inhibitors.
Dr. Ruben Mesa
How JAK Inhibitors Work
Ruth: We currently have four FDA-approved JAK inhibitors, including momelotinib, which was approved in September 2023. How do JAK inhibitors work? For each of the approved JAK inhibitors, would you explain what their benefits and limitations are?
Dr. Mesa: In myelofibrosis, there are three main mutations that we believe are involved with causing the disease. The JAK2 or the JAK2 V617F, the mutation in calreticulin, and the mutation in MPL. There’s even a small subset of people who do not have one of those three.
All of those mutations lead to the same outcome: an overactivation of the protein JAK2. JAK2 is one step. It’s an on-off switch stuck in the on position telling cells to grow.
JAK inhibitors help to decrease the activation of JAK2. Regardless of which of those mutations a patient has or even if they don’t have one of those three mutations, they all seem to benefit from JAK inhibitors.
Ruxolitinib has been approved since 2011. It improves the spleen and symptoms, may help patients who respond live longer with the disease, and in many ways has long been the standard. It’s frequently been used as the base in combination trials.
Fedratinib has been approved since 2019. It can be used to improve the spleen or symptoms. It may be used in the front-line setting instead of ruxolitinib or in the second-line setting if someone has had ruxolitinib already.
Pacritinib was approved in 2022 and this one has a little distinct profile. It’s particularly helpful for decreasing the spleen and symptoms but for individuals with a very low platelet count.
Both ruxolitinib and fedratinib are approved for individuals with a platelet count above 50,000. Pacritinib can be helpful in anyone, but its particularly unique niche is in individuals under 50,000 and we certainly will consider it for individuals with lower blood counts.
Momelotinib was approved in September 2023. This can improve the spleen symptoms and anemia. It showed the strongest improvement in anemia compared to the other three. Pacritinib sometimes can have an improvement in anemia. Unfortunately, both fedratinib and ruxolitinib sometimes can have anemia as a side effect or worsen anemia and rarely would improve anemia.
There are some differences among the four of them, but they overlap in many ways in terms of improving the spleen and symptoms and can be beneficial regardless of the mutation profile that a patient with myelofibrosis has.
Ruth: It’s very exciting for the MPN community to finally have so many treatment options. People often think that because they have mutations other than JAK2, a JAK inhibitor won’t help them so thanks for noting that that’s not necessarily the case.
It’s really exciting now that we have four different JAK inhibitors so we can try to tailor the best JAK inhibitor for the person upfront.
Dr. Angela Fleischman
Navigating Treatment Options
Ruth: Dr. Fleischman, here’s a loaded question. How do you know which JAK inhibitor may or may not work and which one to try first?
Dr. Fleischman: This is an evolving topic. It’s really exciting now that we have four different JAK inhibitors so we can try to tailor the best JAK inhibitor for the person upfront. Sometimes it’s a hit or miss but, as Dr. Mesa described, each JAK inhibitor has a little bit of a different profile.
All of the JAK inhibitors inhibit JAK2 but each one has “off-target” effects and some different proteins and that may explain why they have their own unique profile.
Each myelofibrosis patient is quite unique so they have different needs. For example, for somebody who has an enlarged spleen, with symptoms, and pretty robust blood counts, ruxolitinib would be a great option, which is also the only JAK inhibitor currently approved for PV, in which the purpose is to bring down blood counts.
If the person’s primary problem is anemia, which is unfortunately a very common problem in myelofibrosis, it’s very exciting that we have an option that’s specifically designed for patients with anemia. That’s a patient population very, very appropriate to start pacritinib first.
Many patients with anemia also have a low platelet count. What do you do for somebody who has both anemia and a very low platelet count? We’re going to have to learn how to sequence and make decisions between pacritinib and momelotinib. For a myelofibrosis patient with both anemia and thrombocytopenia or low platelet count, the two options that exist upfront are momelotinib and pacritinib.
Different tiers of needs as we talk about individual clinical trials.
Dr. Ruben Mesa
Combination Therapy Clinical Trials
Ruth: Some of the most exciting clinical trials for MF patients are for combination therapies. Dr. Mesa, can you explain the idea behind combination drug approaches and who might benefit?
Dr. Mesa: We think about different populations of patients. We have those who are JAK inhibitor naive or individuals who have not had a JAK inhibitor yet. This may be at the time of diagnosis or individuals who have had the disease for a while, have been observed, and now, based on spleen symptoms or changes, need to begin therapy.
There are individuals who have been on a JAK inhibitor and have had some benefit, but we feel that there’s an opportunity for further benefit. Some of these individuals are participating in add-on studies where you have a JAK inhibitor that they’ve been on for a while, they have a partial response, and a second drug is added.
The third type of patient is an individual who was on a JAK inhibitor and now no longer has a benefit from that medication so you are switching them to a different therapy altogether. Different tiers of needs as we talk about individual clinical trials.
Selinexor + JAK Inhibitor
Ruth: Let’s talk about some of those combination trials. There are a number of them where JAK inhibitors are given with the addition of a new agent with a different mechanism of action. Let’s talk about selinexor plus JAK inhibitor.
Dr. Mesa: There’s a whole constellation of different agents that have an impact on different mechanisms of action that are being looked at in combination with JAK inhibitors. This one is a little bit earlier in its development.
It’s an approved drug for multiple myeloma and has been approved since July 2019. It’s an anti-cancer medication. It’s a selective inhibitor of nuclear export. It works on some of the processes within the cell in a different way that we feel may be beneficial in combination.
Data from early studies suggest that there is benefit and it may be more with two drugs than the single drug itself. Whether this will become an option for patients with myelofibrosis, the trials will demonstrate, but it has made an important impact for individuals with myeloma so we’re hopeful that it’ll be helpful in this group of patients as well.
Ruth: It’s great to see when we borrow from different areas of research.
Navitoclax + JAK Inhibitor
Dr. Mesa: This works against a process within cells called apoptosis or programmed cell death. Navitoclax is a cousin of a drug that’s approved for acute leukemia called venetoclax.
In studies with myelofibrosis, navitoclax has shown real activity for decreasing spleen symptoms and potentially impacting the disease and, in combination, to a greater degree than JAK inhibitor alone. We have had patients on large phase 3 trials who have been newly diagnosed as well as other situations so those data are anticipated with great interest.
It may take further time for us to identify which combination is a better fit for a patient. These trials are not necessarily designed to answer that itself.
Dr. Ruben Mesa
Pelabresib + JAK Inhibitor
Ruth: Let’s talk about pelabresib, a drug very close to my heart. That’s the trial I’ve been on for more than three and a half years used in combination with a JAK inhibitor. I understand the results have been very promising. At Weill Cornell, they’re calling me the poster child for this study so I’m very grateful for that. Dr. Mesa, tell us about the MANIFEST-2 trial.
Dr. Mesa: This is probably the furthest along of the combination approaches. Pelabresib is an inhibitor of another cellular process called BET. There’s reason to believe that it may have a very complementary role in inhibiting JAK2.
In the early studies, it appeared very promising in terms of having an impact, perhaps more than JAK inhibition alone or in combination when individuals had failed a JAK inhibitor.
We now have phase 3 trials of patients newly diagnosed or who are JAK inhibitor naive receiving this combination versus ruxolitinib alone. We are looking for information to see the net benefit of using the two drugs.
Are the responses more profound? Do they last longer? Are patients better off? We always weigh any downsides to being on two drugs versus one. There are multiple combinations being tested in parallel. It’s possible that multiple of them may be beneficial. It’s possible that multiple of them could become FDA-approved.
It may take further time for us to identify which combination is a better fit for a patient. These trials are not necessarily designed to answer that itself. They’re designed to answer if they are better than a JAK inhibitor alone.
Downstream, we’ll have a better understanding based on specific patient features or other aspects of their health whether one of these combinations may be a better choice for one patient versus the other.
Ruth: Dr. Fleischman, what should patients be asking their doctors to understand if one of these combination therapies might be best for them?
Dr. Fleischman: Entering into a clinical trial is a personal decision for the patient and deserves deep thought. There are many reasons why somebody may want to do a combination therapy. It’s not only because your current therapy isn’t working or that you want something “new” but also to help other people.
Clinical trials are not necessarily only supposed to be for the benefit of the patient themselves, but by participating in a clinical trial, the patient is increasing our knowledge of whether specific combinations work, the appropriate dosing, and the side effects. You’re helping other patients who will come after you.
Cancers are pretty smart that if you target one, they’re going to find a way to get themselves around that medicine you’re giving them.
Dr. Angela Fleischman
Trials Beyond JAK Inhibitors
Ruth: We go into clinical trials often because we were on Jakafi or another treatment and it wasn’t effective, caused side effects that were serious and needed to be discontinued, or maybe it worked for some time and then stopped. Dr. Fleischman, can you talk more about aiming to introduce non-JAK inhibitor treatments?
Dr. Fleischman: JAK inhibitors are very good in terms of reducing inflammation and reducing spleen size and, in some patients, can work very well for a period of time.
Patients could get “resistance.” Resistance with JAK inhibitors is very different than what we think about with other cancers. People on JAK inhibitors don’t develop new mutations that make them “resistant” to the JAK inhibitor. They start to not work as well so that would be one reason to add on and target different pathways.
Myelofibrosis is very heterogeneous. Each patient is very different. Each patient may have different mutations. They may have either JAK2, calreticulin, or MPL, but some patients will have additional mutations that make them look a little bit different than other myelofibrosis patients.
Trying to target multiple pathways, as Dr. Mesa had mentioned, is a very common technique. Cancers are pretty smart that if you target one, they’re going to find a way to get themselves around that medicine you’re giving them. They’re quite ingenious and able to grow despite our single treatments. Each myelofibrosis patient is very different so identifying what the appropriate second agent would be is really on a case-to-case basis.
Part of the challenge that we have with medicines against blood cancers or cancers is finding ways to deliver medicines solely to the cells affected by the disease without harming normal cells.
Dr. Ruben Mesa
Ruth: What’s exciting to see is that we’re more forward-thinking in our endpoints of clinical trials so we’re looking more at survival and not just symptom relief.
All of the clinical trials that we’ve talked about so far are exploring new drug treatments. There are also trials that look at lifestyle issues like exercise or the benefits of yoga and meditation.
Dr. Fleischman is renowned for her work studying inflammation and diet. She and her collaborators recently published the results of a clinical trial that tested the feasibility of the Mediterranean diet for MPN patients.
For those of us living with an MPN, anything we can do ourselves to potentially control our symptoms is very welcome. In fact, it helps us feel in control of our own blood disorder. Even if it’s only a little bit, it’s important.
Dr. Mesa, let’s move on to an area of treatment that the MPN community is very excited about exploring, which is a novel therapy targeting calreticulin, the CALR mutation, one of the most common drivers of essential thrombocythemia and myelofibrosis. People are calling this a potential vaccine. What can you tell us about this that explains it best?
Dr. Mesa: About a third or more of patients with myelofibrosis have a mutation in the protein called calreticulin. This is a little different from JAK2 and MPL because calreticulin might be on the surface of the affected cells and we may be able to target the abnormal calreticulin in a specific way.
Part of the challenge that we have with medicines against blood cancers or cancers is finding ways to deliver medicines solely to the cells affected by the disease without harming normal cells. In the bone marrow, that’s particularly important.
There has been a great interest in seeing if we can target calreticulin in a specific way. A vaccine trial has been done in Europe and is in its infancy.
There’s a theme of multiple different approaches being developed, both cellular-based therapies, such as CAR T or vaccines, or a monoclonal antibody against calreticulin. That is creating great interest but has not yet started in human trials. In the laboratory, it appears to be a very promising medicine.
We’re very hopeful, but we also recognize that until we’ve started treating patients, we never know how good a fit it’s going to be, if there’s going to be an unexpected side effect, or if it will have the benefit that we hope that it has.
I certainly hope that this medication is successful. Even if it is not, I suspect there will be others behind it that hopefully will be. We learn from trials whether they end up being a home run or not. This theme of us trying to selectively target the cells involved is really key.
As we think about anemia, there are JAK inhibitors that can have an impact on the spleen and symptoms, but they may either worsen anemia or not improve anemia.
Dr. Ruben Mesa
Treatment for Patients Who Suffer From Anemia
Ruth: Dr. Mesa, as we know, anemia is very common in myelofibrosis and many people need regular transfusions so this isn’t something that’s likely to go unnoticed. There can be severe fatigue associated and MF patients will have regular blood tests so in theory, it should be seen and diagnosed early on. Tell us about some of the new hopeful treatment options for MF patients who suffer from anemia.
Dr. Mesa: Anemia is when an individual has fewer red blood cells than they’re supposed to. Red blood cells carry oxygen from our lungs to the rest of the body so that’s key for us in terms of our muscles to work well and for us to feel well. That’s why we can have issues in terms of anemia.
Myelofibrosis anemia has multiple aspects. There can be baseline anemia because the bone marrow is not producing enough red blood cells. There can be other contributors if they’ve had baseline iron deficiency that contributes to that. If the spleen is very enlarged, it can hold on to many red blood cells.
Historically, we’ve had a range of options. None of them have been overly dramatic in terms of their impact, but they can help. Injections such as erythropoietin-stimulating agents and androgens like testosterone help to produce red blood cells in both men and women.
There are medicines that are in development. Luspatercept, a medicine that can help with anemia, is currently in phase 3 clinical trials for patients with myelofibrosis. Momelotinib, which was most recently in September 2023, is a JAK inhibitor that can also help to improve anemia.
We look for that medicine to improve both spleen symptoms and anemia. As we think about anemia, there are JAK inhibitors that can have an impact on the spleen and symptoms, but they may either worsen anemia or not improve anemia. Both things can be present.
Momelotinib is an important advance. I hope that as we see other combination therapies, we may see broader improvement in spleen symptoms and anemia.
Should momelotinib or those agents that are more helpful with anemia, perhaps even pacritinib, be that JAK inhibitor to be used with other medications in combination? That has yet to be answered with some of these combinations.
Some real progress in anemia and improving anemia can clearly have a benefit, in terms of the patient’s quality of life and their ability to have enough energy to do their daily activities or things they enjoy, as well as being easier on the body.
One area that we’re intensely working on is trying to identify surrogates for survival or something that we can capture with data amenable to a clinical trial that will be a marker for disease impact.
Dr. Angela Fleischman
Symptom Control While Being on Treatment
Ruth: Dr. Fleischman, what I find very exciting in today’s clinical trials is that we’re moving beyond symptom management and moving more toward progression-free survival, living longer with a high quality of life. When evaluating clinical trials, it’s important to understand the goal of the study. Where do you think we are with this?
Dr. Fleischman: That’s a very important point. For a clinical trial, you need to have an endpoint, a defined thing that you’re going to test. Ideally, something that you anticipate that your drug of interest is going to achieve better than the comparator.
Classically, in myelofibrosis, we’ve focused on spleen volume reduction and symptom burden because those are two things that we can quantify and expect to see a change in a short period of time. Although spleen size reduction and symptom burden are extremely important, they just don’t capture the whole picture of myelofibrosis.
The endpoint of survival obviously is extremely important to myelofibrosis patients. Survival is extremely important to everybody. But because, in general, myelofibrosis patients live a long time, it’s not a feasible outcome for clinical trials.
One area that we’re intensely working on is trying to identify surrogates for survival or something that we can capture with data amenable to a clinical trial that will be a marker for disease impact.
There are some clinical trials such as the imetelstat clinical trial in which survival is the actual endpoint, which is a unique and forward-thinking endpoint. One of the key areas of need in myelofibrosis is identifying markers that can be used in clinical trials that indicate a significant impact on the disease that goes beyond reducing spleen size and symptoms.
Ruth: We’re definitely getting into a very exciting time that will make such a difference therapeutically once we have those answers.
A transplant itself is an extremely risky procedure that can lead to significant side effects or even death.
Dr. Angela Fleischman
The Best Time to Get a Stem Cell Transplant
Ruth: When is the best time to get a stem cell transplant? I know there isn’t a black-and-white answer, but Dr. Fleischman, how do you answer this common question?
Dr. Fleischman: That is another million-dollar question in myelofibrosis and I think the most difficult decision for a myelofibrosis patient as well as for the physician.
As we know, at this point in time, a bone marrow transplant is the only curative option for patients with myelofibrosis. You may say, “If it’s curative, why doesn’t everybody just get a transplant?”
Transplants themselves can be quite risky. The media may miscommunicate transplants. You always see on the news that somebody’s looking for a donor so it may seem that the only problem with transplants is you can’t find a donor. That’s not necessarily the case.
A transplant itself is an extremely risky procedure that can lead to significant side effects or even death. We don’t want to give somebody a transplant if the transplant is going to make them sicker or potentially lead to their death earlier than would be the case if they just treated their myelofibrosis through other means.
The ideal time to transplant is when you get clues from this myelofibrosis patient that with standard treatments, they are very likely going to have an extremely bad outcome or will have an outcome that will lead to their death very quickly. That’s the time going forward with a transplant is worth the significant risk.
The safer the transplant becomes, the greater the consideration of when it is used.
Dr. Ruben Mesa
Dr. Mesa: There is a balance between a patient undergoing a stem cell transplant and a medical treatment. They have very different dynamics. A stem cell transplant can potentially be curative but can come with significant risks, including upfront risk.
The benefits of medication depend on many things, like how much benefit, how long is that benefit, and the impact on the patient. I would certainly view it as a success if we are able to have medicines that are sufficiently impactful that it leads us to either be able to skip a bone marrow transplant or delay it further.
We have precedent in other areas and the most successful example is in chronic myeloid leukemia. At the beginning of my career, most young patients had a stem cell transplant. Now, with the impact of medications, it is rare for patients to have a stem cell transplant because of the effectiveness of medications.
Currently, we are not there yet. A patient who clearly needs a transplant still will go for a transplant. Over time, there may be more combinations of both. Can the medicines help to decrease the burden of the disease and make the likelihood of success with the stem cell transplant greater? That is also a win.
In parallel, there’s tremendous research from our colleagues who do stem cell transplants to try to make that process safer. The safer the transplant becomes, the greater the consideration of when it is used.
It continues to evolve. We reevaluate every option we have. Does that change the dynamic in terms of transplantation as well as how the two things work together? With our current medicines, we are not changing our decisions for transplant, but increasingly, almost all patients that go to transplant have had at least one or more of the JAK inhibitors ahead of time.
The data would suggest that the outcomes with transplant are better in part because of JAK inhibitors but also because of improvements in the processes, antibiotics, other medications, and expertise of our colleagues who run transplant centers.
Asking About Clinical Trials
Ruth: When should a patient ask about clinical trials? How and when do you introduce the idea of considering a clinical trial to your patients?
Dr. Mesa: Clinical trials may exist in any aspect of the disease, from diagnosis to initial treatment to treatment downstream. It’s always a fair question for patients to ask. Is there a clinical trial that may be appropriate for me? It is not limited to one segment of the disease.
Clinical trials are how we make progress. They are highly regulated and always have the needs of the patient front and center. At a minimum, a patient is always getting the option that is at least as good as the standard of care.
It’s a fair question to ask at any point along the way. Truly, all the options we currently have have only been possible because of patients’ willingness to participate in clinical trials.
As physicians, we are happy to have another set of eyes look at the patient and hear another person’s thoughts. That is in no way hurting your physician’s feelings by seeking out a second opinion.
Dr. Angela Fleischman
Dr. Fleischman: This may be a different answer than one may get in a community practice. When I approach a new patient and we talk about treatments, I’ll always talk about standard-of-care treatments first and give people their options, and the pros and cons of each of the standard treatments.
Afterward, we’ll discuss potential clinical trials that the patient might be eligible for. I talk about clinical trials at my own university or elsewhere that I think would be appropriate for the patient. If there was something specific that I thought the patient would be ideal for, we’d talk about that trial first.
Because I want to give the patient all of the information, I would talk about other clinical trials that the person may be eligible for. I would give them reasons why they might be a good idea but also why I don’t think that clinical trial would be ideal for them and give them specific reasons why.
I highly recommend second opinions or even third opinions. Sometimes patients feel bad going for a second opinion. Their primary oncologist may think that they are not happy with their approach. That is not the case.
As physicians, we are happy to have another set of eyes look at the patient and hear another person’s thoughts. That is in no way hurting your physician’s feelings by seeking out a second opinion.
I highly recommend a second opinion or a third opinion, even if it’s just, “I want to learn more about my disease. I’m happy with my treatment now, but I want to get somebody else’s point of view, learn about my future, and what might the options be if this happens or that happens.”
All drugs must move through the steps or phases to ultimately be approved by the FDA.
Melissa Melendez
Trial Knowledge #1: Phases of Clinical Trials
Ruth: Melissa, clinical trials try to see if we can improve the standard of care and give more and better options to more people.
There are different phases of a clinical trial. What are they and what do they mean?
Melissa: I like to think of clinical trials as steps to drug approval. All drugs must move through the steps or phases to ultimately be approved by the FDA. If drugs are studied in new combinations or in diseases outside of their approved indication, they still need to go through all the phases.
For phase 1 trials, the treatment is tested in a very small number of patients. It could range from 20 to 40 patients. We’re testing dosage and looking at the safety and side effects.
Phase 2 trials typically build on phase 1 results. They try to determine the effectiveness and safety of the drug in a specific population. We’re trying to answer the questions of whether a treatment works and how well it works.
For example, there may be a phase 1 trial that tests a drug in blood cancer patients or MPN patients. After the phase 1 results, they determined that myelofibrosis patients showed the best response to the drug. The phase 2 trial now might only include myelofibrosis patients and they’ll be testing it in a larger subset, like 100 to 300 patients.
Researchers continue to monitor patient safety throughout the phase 2 trial and phase 2 studies with positive results will then move into the phase 3 trial.
Phase 3 trials are often referred to as randomized trials, comparing a new treatment against the best standard treatment. These trials can be done with anywhere from 300 to 3,000 participants. Researchers are trying to see if a new treatment has better survival outcomes and fewer side effects.
When a trial is completed and shows that the drug is in fact better than the standard of care or the best standard treatment, that’s when the newly investigated drug becomes a standard of care and will become FDA-approved.
By the time a clinical trial enters phase 4, the FDA has already approved the treatment. These trials are done in thousands of patients and they usually go on for many years.
Placebos are not typically used with patients in cancer clinical trials. But if a placebo is used, the person will also receive the standard treatment for their specific cancer.
Melissa Melendez
Trial Knowledge #2: Use of Placebos in Clinical Trials
Ruth: This one needs myth-busting. A lot of patients and care partners say, “I wouldn’t want to risk getting a placebo.” Are placebos used in myelofibrosis clinical trials?
Melissa: Ruth, I’m really glad you asked that because federal regulations require patients to know if a placebo, which is an inactive substance that looks the same as the one used as treatment, will be incorporated into a trial. An example of a placebo could be a sugar pill.
Placebos are not typically used with patients in cancer clinical trials. But if a placebo is used, the person will also receive the standard treatment for their specific cancer. In our case for myelofibrosis patients, the placebo will be in combination with active drugs so patients are receiving at least the standard of care. No one with active cancer would be treated with only a placebo because that is unethical.
When researchers do use a placebo, they must tell the patient that they have a chance of getting a placebo and that they will receive an experimental treatment at some point in the clinical trial, if not right away. For example, you may be assigned to the placebo group, but if your cancer gets worse, researchers will switch you to a study drug or new treatment.
The more you ask and open up the lines of communication with your team about potential treatment options, the more you learn.
Melissa Melendez
Trial Knowledge #3: Finding Clinical Trials
Ruth: For people who want to explore clinical trials, what can they do to find one for themselves? The ClinicalTrials.gov site isn’t the most user-friendly and that’s why the LLS Clinical Trial Support Center is in existence and is so important. Tell us about that.
Melissa: I agree that ClinicalTrials.gov isn’t the most user-friendly and can be difficult to use. ClinicalTrials.gov is a searchable registry and database of clinical trials conducted in the United States and around the world. It can be overwhelming and this is where the patient’s healthcare team and the CTSC can come into play.
Patients can talk to their doctors and learn more about clinical trials done at their home institution or outside of it. The more you ask and open up the lines of communication with your team about potential treatment options, the more you learn. This can help you better understand what options are available to you and feel more comfortable moving forward with a treatment plan.
The LLS created the Clinical Trial Support Center to arm patients with information to take back to their healthcare team. The CTSC provides a free service to patients. It usually takes under five minutes to fill out a form online. Don’t get overwhelmed. If you’re worried that you haven’t filled out enough information, please submit it anyway.
We reach out to patients within 1 to 2 business days; typically, on the same business day that we receive the referral. When you connect with one of the nurses, you can expect a teammate who will join you on your cancer journey.
We take your individual needs into account. We learn about your treatment goals. We educate the patient about trials and conduct a clinical trial assessment. This includes addressing barriers, such as travel, and discussing financial assistance through LLS or even outside organizations.
We search for trials and go through each one individually, which is a little bit different than other online services. We take an individualized approach and only send trials to patients that they’re likely eligible for. We send the results to the patient and encourage them to take them back to their doctors to discuss the results.
We provide patients with a non-biased, patient-friendly list of appropriate clinical trials. Ultimately, we work in collaboration with the patient’s healthcare team to decide if a clinical trial is right for them. We offer to reach out to the trial sites if there’s anything on the trial list that they would like to learn more about.
We have many patients that we’ve worked with for several years and developed a personal connection with them. We really strive to provide continuity of care throughout their journey. I always tell my patients that I’m just a phone call away and they can always reach out to me at any point with questions or if their disease or treatment changes.
Over time, trials may change. Additional trials may open up or some may have closed so I want to make sure that I can provide them with an updated search any time.
Our services are available to myelofibrosis patients as well as other blood cancers ranging from pediatric patients to adult patients. We even encourage healthcare providers to reach out to us. We do clinical trial searches for physicians in large centers and smaller community centers where they don’t have as many resources or staff.
The clinical trial landscape is pretty complicated. CTSC nurse navigators are here to break down the barriers to clinical trials that patients face to help them make informed decisions. We’re here to help and welcome any patient referrals.
We learn about each patient and take a personal approach to find out their treatment goals, their physician’s goals, and what they’re looking for in a trial.
Melissa Melendez
Trial Knowledge #4: Staying in a Clinical Trial
Ruth: What are the top three things that you do at LLS to help people stay in a trial? Talk about the challenges and the solutions.
Melissa: We learn about each patient and take a personal approach to find out their treatment goals, their physician’s goals, and what they’re looking for in a trial.
Barriers are the first challenge. Nurse navigators are proactive during those conversations on breaking down barriers that patients might face. Are these barriers financial? Will they have to travel if we find one that they’re interested in? Our solution to these issues is to find out if a trial offers financial assistance in addition to what we may offer at LLS.
We email trial coordinators and principal investigators and inquire about the treatment schedule. How many visits may the patient expect? Can they get labs at their home institution?
This is also dependent on what phase the trial is in. This may not be possible for phase 1 trials, but more possible for phase 2 or phase 3 trials. Can any of the long-term follow-up visits be virtual?
Communication is also another challenge. Our solution in the CTSC is to help break down the intimidating medical language or trial jargon. We try to use the simplest explanations and if patients want more in-depth or complex information, we can definitely adjust and provide that as well.
We always check on a patient’s understanding. When we’ve explained something or provided information, we may ask the patient to repeat what they understood and listen as they walk through that process with us. The more they understand, the more comfortable they feel when they’re making the decision.
Trial awareness is a challenge and we can help raise awareness through programs like this. We talk about trial myths and help patients understand the clinical trial landscape better. We help patients be more well-informed about trials that may be available to them and about personalized trial services like ours and the Clinical Trial Support Center at LLS.
At the LLS, our main hub is our information resource center through our information resource specialists, nurses, and social workers. You can call the 1-800 number Monday through Friday, 9 a.m. to 9 p.m. Eastern Standard Time.
We also have a chat option where you can do a live chat online, and that’s Monday through Friday, 10 a.m. to 7 p.m. Eastern Standard Time.
If for some reason you reach out to us outside of our business hours, you can always leave a message 24/7 and we’ll give you a call back.
We’re in a very exciting time for myelofibrosis… We can personalize FDA-approved JAK inhibitors for each myelofibrosis patient.
Dr. Angela Fleischman
Final Takeaways
Ruth: If you could leave people with just one message, what would that be?
Dr. Mesa: I would leave them with a message of hope. We have made a tremendous amount of impact and a much greater understanding of the biology of the disease, the genetic mutations, and why people progress. We are building on a base of very good medicines that have made an impact with the JAK inhibitors but to a new era of multiple different approaches.
I would heavily encourage patients to consider clinical trials where appropriate. Clinical trials will build on the base of these medications to try to drive progress further and further. We need your help and together we will continue to improve the therapy of diseases like myelofibrosis.
Dr. Fleischman: We’re in a very exciting time for myelofibrosis. In the past few years, we’ve moved from a single FDA-approved JAK inhibitor to four JAK inhibitors. We can personalize FDA-approved JAK inhibitors for each myelofibrosis patient.
There are a lot of opportunities for combination treatments that are moving forward in clinical trials as well as going beyond JAK inhibitors, trying to identify other key pathways to target myelofibrosis.
Melissa: In the CTSC, we educate, support, and empower myelofibrosis patients as well as other blood cancer patients to be active participants and have control over their treatment decisions with their healthcare team.
The Leukemia & Lymphoma Society wants to make a difference in patients’ lives through research, advocacy, education, support, and financial assistance. We want to see a future without blood cancers. We have a lot of free information for patients, caregivers, and healthcare providers to check out.
We’re a phone call away and we are here to help make clinical trials less overwhelming for patients and to help healthcare providers.
Ruth: We have covered an awful lot of information and invaluable insight from our experts. I know I speak for people living with ET, PV, and MF, their loved ones, and care partners when I offer our very sincere gratitude to you all for everything you do for our community.
Stephanie: Thank you so much, Ruth. I always appreciate the way you bridge the conversation for us.
Thanks so much to Drs. Mesa and Fleischman for the work that you do in the clinic and in research to help patients and families who are trying to navigate a myelofibrosis diagnosis and treatment, and all the decisions that come in between.
Thank you to our LLS clinical trial nurse Melissa Melendez for being there day to day and helping people who are overwhelmed by the topic of clinical trials.
We really hope that you walk away with a greater understanding of clinical trials in myelofibrosis. We hope to see you at a future program.
Special thanks again to GSK for its support of our independent patient education content. The Patient Story retains full editorial control.
Learn about new multiple myeloma treatment classes and combinations, including advances in BCMA-targeted therapies, like CAR T-cell therapy and bispecific antibodies. Find out the future of belantamab mafodotin combinations in relapsed/refractory multiple myeloma. Acquire clinical trial knowledge and bust common misconceptions about clinical trials.
Thank you to GSK for its support of our patient education program! The Patient Story retains full editorial control over all content.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Stephanie Chuang, The Patient Story: My name is Stephanie Chuang, founder of The Patient Story. A few years ago, I had a diagnosis of non-Hodgkin lymphoma, but we have so many shared experiences in what we’re looking for.
We believe it’s especially important to have these educational programs specifically for patients, family members, and supporters when it comes to topics like clinical trials, which can sound daunting and have lots of jargon so our goal is to humanize your options.
We’re so proud to be co-hosting this with The Leukemia & Lymphoma Society, a great partner of ours. It’s the world’s largest nonprofit health organization dedicated to funding blood cancer research that is so critical as well as offers patient services and education.
They have great resources, including information specialists who are a phone call away to help answer your cancer questions. We’ll be highlighting the LLS’ Clinical Trial Support Center or CTSC, which is a huge free resource that offers one-on-one support to enroll and stay in clinical trials.
We also want to say a special thanks to GSK for supporting our educational program. Their support helps us make these programs more available and free for our audience. We want to note that The Leukemia & Lymphoma Society and The Patient Story retain full editorial control of this entire program.
This is not meant to be a substitute for medical advice. We want you to walk away and be able to go to your own medical team with questions and more knowledge to make more empowered decisions.
Cindy Chmielewski, Myeloma Patient Advocate
Stephanie: Our first incredible panelist, a myeloma patient voice, and leader in the community, Cindy Chmielewski, will be leading this conversation from this point forward.
Cindy, I know you’re going to share more about your own story and how you became such a passionate advocate, but we would love to learn more about you because as we know, we are so much more than a diagnosis.
Cindy Chmielewski: Hi, everyone! My name is Cindy Chmielewski and I’ve been living with multiple myeloma since 2008. Prior to my myeloma diagnosis, I was a fifth-grade teacher.
Since being diagnosed with myeloma, I realized how important it is for patients to be part of their care and educated so they can be part of the decision-making process. Now I’m using my teaching skills to help myeloma patients learn more about myeloma so they can engage in discussions with their doctors.
Dr. Caitlin Costello, Hematologist-Oncologist
Cindy: We have Dr. Caitlin Costello, a hematologist-oncologist and associate professor of medicine at the University of California San Diego. She specializes in treating blood cancers with a focus on multiple myeloma. She also participates in a number of clinical trials that offer cutting-edge treatment strategies and therapies for myeloma.
Dr. Costello, what drew you to myeloma and what’s your passion for helping patients?
Dr. Caitlin Costello: It’s people like you who draw us into the things we love. Multiple myeloma satisfied a lot of my interests. The science of myeloma exploded during the course of my career, which really satisfies the academic side of my brain.
I didn’t want to go into oncology when I was doing my training. I find such passion and reward in connecting with my patients. At the very beginning of my training, I felt like cancer oncology was not going to allow me to have long-standing relationships with patients because of the biology of the disease and the outcomes associated with it.
I found myeloma and it satisfied both. It let me find that scientific side and let me have enduring relationships with patients as myeloma patients live long with this cancer. Sometimes things fall into place and I’m so grateful for that.
Cindy: I’m so glad that we are living much longer. We do develop relationships with our doctors because we’re in ongoing treatment so we’re seen for a very, very long period of time.
Dr. Landgren, what drew you to myeloma, and what drives you most to continue your work with helping patients?
Dr. Carl Ola Landgren: I’ve been in the field for quite a few years; almost 30 years since I started my career.
When I was in fellowship, the senior doctors were saying there are two diseases you should stay away from, chronic lymphocytic leukemia and multiple myeloma, because there had been so little development in those disease areas.
I thought, That sounds like a really great opportunity. We need to go there. We need to do more investigation and see if we can change that. I was drawn to that and initially started working on both. Over time, I picked multiple myeloma as the disease that I was most interested in.
It’s been spectacular to be part of this journey together with so many other colleagues and friends around the world, with all the development of new drugs, and all the new technologies.
Over three decades, we are at a very different place. I’m very, very happy about it. All my research is centered on patient needs. I’m dedicated to driving the research forward.
Cindy: Thank you for choosing myeloma. We’re very lucky to have you because I’ve seen all the work that you do.
Cindy: I would like to introduce Christen Hawthorne from The Leukemia & Lymphoma Society, a nurse navigator with the Clinical Trial Support Center. Christen, share a little bit about yourself and what made you become a clinical trial nurse navigator.
Christen Hawthorne: I’m originally from northern New York, but moved to Denver, Colorado, in 2015 to pursue a career in cancer care. Since then, I’ve specialized in the area of bone marrow transplants and worked with patients who have a blood cancer diagnosis at different stages in their treatment plan.
My grandfather, unfortunately, passed away from cancer. I was so inspired by the holistic care that he received not only when he was in the hospital but also from my grandmother, who’s a retired registered nurse. Seeing that care and devotion, both professionally and personally, inspired me to pursue a specialty that allowed me to care for people beyond the clinical landscape and really focus on them as a person.
I’ve volunteered for The Leukemia & Lymphoma Society since 2015, fundraising for Light The Night and as an advocate with their Office of Public Policy. Seeing the many different pillars at LLS and how they support patients and families inspired me to pursue a position within the organization, joining the CTSC team in 2022.
Clinical trials and research are critical pillars of cancer care. They are how efficacious treatments are developed with the hope of fewer side effects and better outcomes. I hope I’m able to shed some light on their importance, dispel myths, and share additional resources.
Cindy: The myeloma landscape has changed over the last decade or two for clinicians, researchers, and patients.
When I was diagnosed in 2008, there were very, very few treatment options. Most of what’s available today were not available. Induction therapy was normally a doublet. Eventually, it became a triplet. Now we have quadruplets.
Back in 2015, there was something called the November to Remember and it was in that November when three myeloma drugs got approved within weeks of each other. We had our first two monoclonal antibodies and an oral proteasome inhibitor. It seemed like a great time.
But since then, we’ve had so many more drug approvals that I can’t even keep track of them — CAR T cells, bispecific antibodies, and the next generations of some of our other drugs. It really is an exciting time.
With all these drugs coming into the market, it’s so important that myeloma patients work with the myeloma specialists because there are so many combinations. How do you sequence them? What’s best for you? Are there any biomarkers that will help predict what would be a better outcome for you?
The landscape is changing, which is exciting, but we have a lot of work to do to figure out the best combination for each patient.
Multiple myeloma is technically a cancer of a cell called a plasma cell, which is an important part of your immune system.
Dr. Caitlin Costello
What is Multiple Myeloma?
Cindy: Dr. Costello, can you briefly describe what multiple myeloma is and some of the signs and symptoms of multiple myeloma?
Dr. Costello: It’s so important to do myeloma 101. Patients can advocate for themselves if they understand the basics of the disease.
Multiple myeloma is technically a cancer of a cell called a plasma cell, which is an important part of your immune system.
When they do that, they don’t work like they’re supposed to either. Now you have cancerous plasma cells that are not working the way they’re supposed to and they start producing abnormal proteins.
Your body, your immune system, and your plasma cells are supposed to produce a variety of different proteins or antibodies to fight the bad guys. But when one plasma cell goes rogue and starts copying itself, it starts prioritizing to make one form of those antibodies relative to the rest of them. Those bad antibodies get produced and find a way to run around the body and wreak havoc a bit.
Significant fatigue, shortness of breath, and lightheadedness are some of the most common symptoms that patients come to get medical help for when they’re first diagnosed with myeloma.
Dr. Caitlin Costello
Common Symptoms of Myeloma
Dr. Costello: Myeloma can affect your body in a variety of ways, one of which is having an interest in the bones. There are a couple of different ways it affects the bones. I like to think of it as a little Pac-Man. It takes little bites out of the bones or can almost form little tumors within the bones and that can hurt.
A lot of patients who are first diagnosed with myeloma say, “I have this pain. I don’t know why it’s there and it’s not going away,” and they seek care for that. Sometimes it can take a while to get to a diagnosis of multiple myeloma, but bone pain is a common presenting symptom.
Another common presentation is fatigue and this is hard because we’re all tired; life is hard sometimes. Fatigue can happen because of anemia.
Multiple myeloma is a problem in your bone marrow, which is the factory not only of your immune system but also of your blood. If your bone marrow is busy making cancerous cells, there’s not enough room to make the normal blood you need. That decreased production known as anemia can really produce symptoms of significant fatigue, shortness of breath, and lightheadedness.
Those are some of the most common symptoms that patients come to get medical help for when they’re first diagnosed with myeloma.
Cindy: They were the two symptoms that brought me to the doctor. I had terrible back pain and I was so tired and out of breath.
A big step forward in the field has been the evolution of all the different options. It’s no longer a matter of picking A or B. We pretty much have the whole alphabet to present.
Dr. Carl Ola Landgren
Navigating Myeloma Treatment Options
Cindy: We’ve had a slew of new treatments. When you think about what treatments a person should be on, what are some considerations that you weigh? What do you think about when they’re transplant eligible or ineligible, newly diagnosed versus relapsed/refractory?
Dr. Landgren: A big step forward in the field has been the evolution of all the different options. It’s no longer a matter of picking A or B. We pretty much have the whole alphabet to present.
There are very many options and it starts in the newly diagnosed setting. If someone has a recurrence, there are many options looking at the guidelines that dictate what we’re allowed to prescribe. Based on the NCCN Guidelines, there are over 40 different combinations in the setting of relapsed/refractory disease.
When I have a newly diagnosed patient, I have to think if this person is a potential transplant candidate or not. That has also shifted over the years because we can technically transplant many more patients than we could before. We can transplant people who are older and even those with comorbidities.
On the flip side, I personally think that the need for transplants has probably gone down. There are so many new treatments so we could do more. But in reality, I think we do less and I think the numbers point in that direction as well.
Cindy: I’m glad you include the patient. Shared decision-making is always the best.
We have to understand the difference between a long, durable remission, which means it goes away and stays away for some great period of time, versus a cure, which means it ain’t ever coming back, which is what we’re all aspiring to.
Dr. Caitlin Costello
Working Toward Cure
Cindy: Is there a treatment that can cure myeloma or put myeloma in a really deep remission? A few years ago, doctors were very hesitant to use the word cure. They were talking about controlling myeloma and keeping it at bay for several years, but I never heard the word cure. But more recently, I’ve heard the word cure and doctors are thinking that maybe we are curing some patients.
I talked to lots of patients and one of the most common questions I hear is what treatment works the best. Should I be on three drugs? Should I be on four drugs? What should I have? They also want to know: is there a cure for myeloma?
The words myeloma and cure were never used in the same sentence by myeloma specialists, but things began to change. I started hearing myeloma doctors say, “Yes, I think we may be curing some patients and maybe in 10 years, we’ll be curing more patients.”
Dr. Costello, can you talk about your perspective on a cure for myeloma?
Dr. Costello: This is the other C word. The big C we think about is cancer, but the cure word is becoming something we’re really starting to flirt with. Over the last couple of years, we’ve seen this explosion of new medications.
In the last two decades or so, we have seen the number of options for treatment go from a few to a wide variety of options that let people get into remission and stay in remission for very durable long periods of time. We’re starting to see that happening for such long periods of time that we’re saying, “Is it ever coming back?”
We have to understand the difference between a long, durable remission, which means it goes away and stays away for some great period of time, versus a cure, which means it ain’t ever coming back, which is what we’re all aspiring to.
I think we’re getting there. I always tell my patients, “In my lifetime, we’re going to do this. We absolutely are going to do this.” We’ve seen too much change in the last decade or two decades to not reach that point.
This is not a one-size-fits-all type of cancer. Although multiple myeloma is grouped together as one form of blood cancer, there are very different subtypes and very different forms of myeloma that act differently. Some are easier to treat and may go away, others can be a little bit more stubborn.
When we’re thinking about ideal treatments for any individual person, we have to look at you as a person, your health, your social situation, and your support. Then we have to look at the biology of the disease and put all of that together to figure out the best means of achieving a cure.
With more and more of these drugs delivering great, deep, durable responses, it’s natural for the field to talk about it.
Dr. Carl Ola Landgren
Dr. Landgren: I do think we are heading towards a cure. There are multiple reasons that the field has not talked about that cure for myeloma in the past. Quite frankly, the drugs were not good enough. We used to have 1 or 2 drugs for many years, way before I started practicing.
Then there was the emergence of high-dose chemotherapy with melphalan, the so-called transplant. Then there was the rediscovery of IMiDs with Dr. Bart Barlogie’s discovery of thalidomide that led to lenalidomide and pomalidomide. We had proteasome inhibitors coming around. Then we had all the immunotherapy.
The field has evolved. We see many patients achieving remissions and minimal residual disease (MRD) negativity so there is no detectable disease. When you don’t have those perspectives, it’s not really something brought up frequently with cure. With more and more of these drugs delivering great, deep, durable responses, it’s natural for the field to talk about it.
There is really no definition in the literature. What is the definition of cure? It’s true for any disease. If you were to survey myeloma experts and ask how they define cure, you would probably get very different answers.
If you ask me what I think, someone who has been treated with effective therapy and repeatedly shows no detectable disease is, at some point, probably cured.
If you put me on the spot and say how long that window is, then I will start going back and forth but maybe five years or so is a reasonable endpoint. Can you be 100% sure that the disease will never come back? Probably not, but life is filled with a lot of unknowns.
Many patients in my clinic are cured. Many of those patients come from Dr. Barlogie, who used to treat a lot of patients in Arkansas. He gave every drug under the sun. When he moved to New York, I was the chief of the Sloan Kettering myeloma program then he retired. When he retired, many of those patients were looking for another doctor and came to me. Then I moved to Florida. Many of those patients followed me to Miami.
I had many of his former patients who were treated for five years and then stopped treatment. I have patients who have been off treatment for 20 years. They remain off treatment and are doing very, very well.
Cindy: Thanks for giving me hope that you think there’ll be a cure in my lifetime so that makes me smile.
All drugs have to move through steps or phases to ultimately be approved by the FDA.
Christen Hawthorne
Trial Knowledge #1: Phases
Cindy: We have a new section called Trial Knowledge where we’re going to give you some knowledge about clinical trials and maybe do some myth-busting of things we’ve heard.
Christen, there are different phases of clinical trials. Can you talk about what happens in each of those phases?
Christen: I like to think of clinical trials as steps to drug approval. All drugs have to move through steps or phases to ultimately be approved by the FDA. If drugs are studied in new combinations or in diseases outside of the approved indication of the drug, they still have to go through these phases.
In phase 1, we’re investigating the safety, side effects, dosing, and best way to administer treatment. This is usually in 20 to 100 patients.
In phase 2, we’re determining the effectiveness and safety of the study drug in about 100 to 300 patients.
In phase 3, we’re looking at the effectiveness, side effects, and safety of the study drug in comparison with other treatments. This includes anywhere from a few hundred to a couple thousand patients.
No one with active cancer would be treated with only a placebo as that is unethical.
Christen Hawthorne
Trial Knowledge #2: Placebo
Cindy: One thing I hear from lots of patients and care partners is that they really don’t want to consider clinical trials because they’re afraid that they’re going to be given a placebo. With cancer, you don’t want to be given a placebo. Can you talk about placebos and how they are used in cancer trials?
Christen: It’s definitely a common one that we get from our patients.
Federal regulations require patients to know if a placebo or a substance that looks the same as the one used in the treatment but is inactive will be used in a trial. Placebos are not typically used with patients in cancer care trials. The decision of whether to use a placebo in a clinical trial is based on how serious the illness is or if the disease is life-threatening.
Patients with these types of diseases are given the best available treatment or standard of care instead of a placebo. If used in cancer clinical trials, the placebo will be in combination with active drugs so you’re at least receiving the standard of care. No one with active cancer would be treated with only a placebo as that is unethical.
Cindy: It’s good to know that if there is a placebo, it’s in addition to the standard of care that you normally would be receiving. You will never be given just a placebo alone.
Clinical trials are a very complicated care landscape to navigate. The mission of the Clinical Trial Support Center is to help patients and caregivers identify potential clinical trials and overcome the barriers to enrollment.
Christen Hawthorne
Trial Knowledge #3: Finding Clinical Trials
Cindy: Christen, how do patients find clinical trials? I know there’s ClinicalTrials.gov, but it’s not the most user-friendly. You might end up with hundreds of trials when you search for them and you won’t know what’s right for you. Can you talk about how The Leukemia & Lymphoma Society can help?
Christen: Clinical trials are a very complicated care landscape to navigate between understanding what institutions are participating in certain trials, their inclusion and exclusion criteria, and what might be the best match for your unique profile. It can be really overwhelming.
The national average of cancer clinical trial enrollment is only between 5 and 10%. We found that, on average, our team has 22 interactions on behalf of a patient from the initial assessment to the time of enrollment — that’s 22 potential holes in the road where patients or caregivers could fall through. We’re able to fill those holes in 23% of eligible patients that we work with enroll in a clinical trial.
Resources within the LLS, including the Clinical Trial Support Center, collaborate with your care team, helping equip you with the knowledge to support you and to help you feel confident in making an informed decision about your care.
Our support center is a team of nurses and nurse practitioners who work one-on-one with you and your family to understand your unique clinical situation while getting to know you as a human, providing support that aligns with your goals of care.
Our mission is to help patients and caregivers identify potential clinical trials and overcome the barriers to enrollment.
We start with an initial conversation to learn more about you, your goals of care, your treatment plan, and your past medical history. From there, we begin a search based on the information provided, including ability and willingness to travel, insurance concerns, and any other factors specific to you.
Once our search is complete, we provide a comprehensive but easy-to-digest list of potential trials and resources to review with your care team. If there is an appropriate trial to pursue, we can reach out to the clinical trial sponsor or specific site with any questions or find out the next steps to enroll on your behalf. Throughout this process, we remain available to support you and answer questions along the way.
You can connect with one of our information resource specialists. They are happy to assist you in filling out the form and we can connect to get to know you and do a thorough assessment.
Cindy: Sometimes staying on a clinical trial may be difficult. Can you explain some of the things that the LLS can do to help patients stay on a trial?
Christen: In the Clinical Trial Support Center, we’re able to understand your unique clinical situation before providing a comprehensive list of trials to review with your care team. We also provide continuity of care by working with you and your family throughout your diagnosis and this could be months to years long. We continue to understand your evolving goals and tailor our support to meet them.
We do have regular meetings with sponsors of clinical trials to understand patient requirements of the trial and if there are additional support opportunities for patients or families to cover travel and lodging expenses associated with trial participation.
While we provide education and resources to our patients within the CTSC, we also have an incredible network of information resource specialists, the financial assistance department, and patient and community outreach managers who can help support patients throughout their care plans in unique ways.
Clinical trials exist at every part of the journey with myeloma and they really offer opportunities for patients.
Dr. Caitlin Costello
Clinical Trials for Newly Diagnosed Patients
Cindy: A newly diagnosed patient is someone who’s just starting treatment. In my mind, I always thought that clinical trials would be for later down the line when you’re running out of treatment options.
Dr. Costello, can you talk about trials for newly diagnosed patients?
Dr. Costello: Clinical trials exist at every part of the journey with myeloma and they really offer opportunities for patients. Like Christen beautifully said, you’re either getting the standard of care or you’re getting something that might be better so it gives patients opportunities for the next new and cutting-edge treatments.
In the last few years, we’ve had the outcomes of some of these newly diagnosed trials, particularly the ones that finally are getting published. One was the GRIFFIN study. As Cindy mentioned previously, two drugs are good, three drugs look better so maybe four is the best.
When someone’s newly diagnosed, our usual cocktail is three different drugs together. But what if we give them four? Does that have better outcomes and more likelihood of achieving remission? Does it get us more durable remissions where people are staying in remission longer?
We have the final analysis published that showed us that those patients who get four drugs when they’re first diagnosed have deeper and more durable remissions than those who get standard of care. Our standard of care of three drugs now seemed outdated.
It’s in recent years that we’ve said four drugs are the way to go. This is specific to younger and/or healthier patients. Age is just a number. The reality is some intensive therapies may be too much for a patient depending on their health or other medical issues that they may have.
If we find the next new and exciting thing for someone younger and/or healthier, the next question is: what about someone who may not be as young or as fit or possibly more frail?
The triplet combination that came out of the MAIA study combined three different drugs, which we proved was better than two different drugs. To say that, though, that cocktail truly has exceedingly, exceedingly effective outcomes for patients who may be older or more frail, for example.
There’s a lot of work that’s been done to get us to this point. We’re so glad that we finally have a new standard of care that we can have future trials use as a baseline to compare to for the next steps to get us to that cure.
Cindy: We’re in exciting times. If you ask different myeloma specialists, they would have different answers about what a cure is. The same holds true for patients. If you ask what they expect in a cure, you might come up with different answers. But to me, it sounds wonderful being treated for a set period of time and then being off drugs for an extended period of time; that would be my definition of a cure.
We need more classes of drugs because if you treat the patient and it works, that’s fantastic. But if the therapy stops working, we need to have other classes of drugs.
Dr. Carl Ola Landgren
Triple-Drug Combination Clinical Trials
Cindy: We’ve been talking about how things have changed. I know when I was diagnosed back in 2008, induction therapy was a doublet. Now, the standard of care is a triplet, but it seems to be moving towards quadruplets.
Before we start talking about quads and the benefits of some of these four-drug combinations, can we focus on some of the clinical trials that are triplet combinations and which ones have been gaining your attention and why?
Dr. Landgren: The bigger triplets that I pay attention to are the RVd or VRd regimen. This is bortezomib, lenalidomide, and dexamethasone. This was initially developed by Paul Richardson and the group at Dana-Farber. It was presented at ASH 2008 and it was published in a small study in 2010 that became the standard in the US, based on a little bit more than 50 patients treated.
Eventually, it was published as a randomized study compared to lenalidomide and dexamethasone. The randomized evidence came many, many years after this had already become a standard of care. That is one of the three-drug combinations that I think are important. They pushed the field forward.
I was involved in the development of the KRd regimen with carfilzomib, lenalidomide, and dexamethasone. The difference between these two regimens is that the proteasome inhibitors are different. You have no added neuropathy with carfilzomib, which you have with bortezomib.
But if you give carfilzomib to a patient with underlying cardiovascular disease, you could push that patient into congestive heart failure. What has been found also is that a lot of this is due to giving too much fluid. But that’s a great, great combination. For patients who are otherwise fit, that would be my go-to therapy.
Then you have the DRd, which is daratumumab or DARZALEX with lenalidomide and dexamethasone. That was approved in 2019. That has been a game-changer. It takes away all the problems with bortezomib’s neuropathy. You replace the proteasome inhibitor with an antibody. Giving a CD38-targeted antibody with lenalidomide and dexamethasone has really changed the field.
It has also erased some of the age discrimination that’s been in the field for a long time where younger patients could get more effective therapies while patients who were older and more frail have very few options. You had only two drugs.
With daratumumab coming, the difference between patients that are frailer, older, or have other issues and patients who are younger and more fit became smaller in terms of efficacious drugs. The addition of immunotherapy has really, really made a huge step forward.
Cindy: How about your thoughts on the trials that are doing selinexor, pomalidomide, and dexamethasone against elotuzumab, pomalidomide, and dexamethasone? Any thoughts on that trial?
Dr. Landgren: Those are combinations in trials for patients who have relapsed/refractory disease. Elotuzumab is a drug that binds to a protein called CS1 or SLAMF7, and it was discovered many years ago.
In the laboratory, this antibody bound to myeloma cells and they died. However, in patients, elotuzumab alone has not been found to have any clinical benefit.
Elotuzumab has been partnered either with lenalidomide or pomalidomide. Given in combination, it has been found to be more efficacious than lenalidomide with dexamethasone alone or pomalidomide with dexamethasone alone. Elotuzumab adds to these backbones.
Selinexor can be used in different combinations. It has been approved with bortezomib and for patients with a first, second, or third relapse. There are other combinations as well with pomalidomide and also with carfilzomib.
Selinexor is a new class of drugs. It binds to a protein that is sent into the center of the tumor cells, the nucleus, so it’s a blocker of certain proteins that go in and out of the nucleus and has been found to work very well in myeloma.
We need more classes of drugs because if you treat the patient and it works, that’s fantastic. But if the therapy stops working, we need to have other classes of drugs.
Cindy: Before we move on to the four-drug combinations, let’s talk about BLENREP or belantamab mafodotin. We had it on the market for a bit and then it was pulled because it didn’t meet one of its primary endpoints, but it’s still in trials, like the DREAMM 8 trial, using BLENREP in combination.
Dr. Landgren: Belantamab mafodotin is an antibody-drug conjugate. It’s a small molecule, a toxin similar to lenalidomide or carfilzomib that can have an anti-myeloma effect. The difference between belantamab mafodotin and these other drugs is the way it’s delivered.
The drug is not given as a tablet, an injection, or an infusion; it’s bound to an antibody and that antibody is infused into the vein. When the antibody comes into the human body, it looks for the corresponding protein that this antibody’s been designed to bind to and that is the BCMA protein that’s widely expressed on the surface of myeloma cells.
When these antibodies find the myeloma cells, they bind to the BCMA protein. Once they have, the myeloma cell lets this antibody in and once it’s in there, it releases this toxin that will kill the myeloma cells. It’s like a Trojan horse.
This is the first and so far only antibody-drug conjugate developed for myeloma. It was approved in 2020 and then pulled from the market in 2022. What happened?
The FDA has a fast track for drug development, which is great for patients. That will speed up the availability of new drugs. A drug company can do all the safety and toxicity data pre-clinically. They can open a phase 1 study and identify the right dose, then you can have an expansion cohort or a phase 2 study and treat a number of patients per agreement with the FDA.
If the right proportion of patients responds to the drug, if the FDA agrees, then an accelerated approval will happen. That’s what happened to most of the drugs. All the drugs we currently have in more recent times have been approved based on this mechanism; that happened to belantamab mafodotin.
When belantamab mafodotin was compared to its control arm, the drug belantamab mafodotin was not superior. When the FDA reviewed the data, they said this study did not live up to its endpoint.
FDA did not stop the drug. GSK, who owns the drug, took it off the market before the FDA made that decision. There was nothing for the FDA to stop because they already took it off the market.
However, in agreement with the FDA, the drug is available for compassionate use. The fact is that the drug works for many patients. If there is a doctor who thinks this is the best option for a given patient here and now, that doctor can reach out to the FDA and get permission to use it.
The FDA has the next rule in place. Once you’re given accelerated approval, you have to design a randomized study where you prove that this drug is superior to a control arm. A randomized study has to be written, launched, and concluded, and the data has to be handed to the FDA.
There are other trials that they had already launched in combination with belantamab mafodotin and there are two of them ongoing. There is a control arm and now it’s belantamab mafodotin in combination.
The study that failed was belantamab mafodotin as a single drug versus a control arm. There are two ongoing trials that use combination therapies versus control arms. When they are done, the data will be handed back to the FDA.
It’s very likely that those trials, one or both of them, may read out with the drug being superior and that could reintroduce the drug and they could get the full approval. We have to just wait and see.
They are part of the DREAMM program. Belantamab mafodotin was initially developed in DREAMM 1 and then there’s been 2, 3, and 4, and so forth. Now we’re up to DREAMM 7 and DREAMM 8.
The trials use belantamab mafodotin. One of them uses it with bortezomib and dexamethasone and the control arm is bortezomib and dexamethasone. The other one uses it with pomalidomide and dexamethasone and the control arm is pomalidomide and dexamethasone.
With all things being equal, I do think that four drugs are here to stay. The GRIFFIN study showed us that it is better than three.
Dr. Caitlin Costello
Four-Drug Combinations for Multiple Myeloma
Cindy: Do you think the four-drug combinations are going to be the new standard of care for newly diagnosed myeloma? If so, which four drugs do you envision to be used as part of induction therapy? How do you weigh the risks and benefits of adding that other drug with the side effects it may cause? Would there be some patients that maybe could still use three?
Dr. Costello: Four drugs are definitely here to stay but not for everyone. We talked about the importance of personalizing this approach and how we take into consideration so many different aspects of you, your health, and your myeloma when we make these decisions.
With all things being equal, I do think that four drugs are here to stay. The GRIFFIN study showed us that it is better than three.
There are more trials coming out. GRIFFIN was a phase 2 trial, which showed us important things, but we want to extrapolate that data to use it in several hundred different patients to prove what was shown in the GRIFFIN study.
The next studies that are coming along, like the PERSEUS phase 3 trial, are going to show us how we can get the durability of response and prove that the initial study, GRIFFIN, was right and is proof that quadruplet or four drugs is here to stay.
Dr. Landgren: Similar to most things in life, there will be early adopters and people who will be the very last people to change their minds. Some people build their career on saying no, no, no all the time and that’s how the field goes.
The three-drug combinations I mentioned before are proteasome inhibitors with IMiDs and steroids, and the evolution has also been CD38-targeted antibodies with IMiDs and steroids.
When we talk about four-drug combinations, it’s basically a merge of those so that means that you add a CD38-targeted monoclonal antibody. For the most part, the studies out there are using daratumumab added to a proteasome inhibitor, IMiD, and steroid. In plain language, you’re talking about Dara-RVd or Dara-KRd; those are the two that have been presented.
There are three trials that have been published so far using those combinations. The first was the Dara-RVd randomized phase 2 study that was published about three years ago in the Blood journal. They wrote the protocol and the lead author is Peter Voorhees.
That had about 100 patients with daratumumab with RVd and about 100 patients just with RVd. Patients receive four cycles of either of the regimens. They were all transplanted then they got two more cycles with the same regimen that they started off with.
After completing the sixth cycle, the study looked to see if there was an improvement in the stringent complete response rate. There was a slightly higher stringent complete response rate if you add the daratumumab therefore the study was deemed successful. Clinically, you could argue: is that really meaningful? But that’s how the study was designed.
Patients who got dara-RVd continued on daratumumab with lenalidomide maintenance for two years. The patients who got RVd got lenalidomide maintenance.
What the study continued to show is that the rate of MRD negativity is much, much higher in the group that started and continued on daratumumab. They have plotted out the progression-free survival curves. The progression-free survival seems to be way superior in the four-drug combination.
But it’s not only the four-drug combination upfront that’s different between the two arms. It’s not four versus three. It’s also the maintenance being very, very different. You could ask the question: what would happen if you gave everybody three drugs to begin with and had a two-drug or one-drug maintenance, would that make a difference? That study has not been done so we don’t know the answer to that.
The other combination is Dara-KRd and I was the lead investigator in the first trial to be published called the MANHATTAN study. I did that when I was at Sloan Kettering. We gave Dara-KRd for eight cycles and patients were not transplanted in that study.
After four cycles of treatment, a patient had the option of collecting their stem cells or not, and after eight cycles, they had the option of being transplanted or not. Some patients were MRD negative and they chose to go for transplant.
The majority of patients who were MRD negative chose not to be transplanted so they kept their stem cells in the freezer. We have kept on following these patients. So far, we have not really seen any significant difference in whether you were transplanted or not, but the study was not designed to fully answer this question.
The third study that used Dara-KRd is the MASTER trial, which was developed by Luciano Costa. He treated a smaller number of patients. Patients got four cycles of Dara-KRd, were transplanted, and if they were MRD negative after each of these two steps, were taken off therapy
If they turned MRD negative, they got another four cycles of Dara-KRd and, again, if they were negative two times in a row, they were taken off therapy. They could get an additional four cycles so they could end up with a total of 12 cycles. Every patient was transplanted in this study.
He has shown that with a relatively short follow-up, patients who didn’t have adverse cytogenetics continued to be free from disease after 1 or 2 or so years, while patients who had more aggressive disease would have their disease flare back again if you take them off therapy. That’s where the field is right now.
From what we’ve seen so far, it’s been a new, wonderful treatment option for myeloma patients.
Dr. Caitlin Costello
CAR T-cell Therapy
Cindy: When I first heard about CAR T-cell therapy, it was when the University of Pennsylvania and CHOP had their first CAR T-cell patient and how well that response was. Can you talk about what CAR T-cell therapy is and some of the benefits of using this type of immunotherapy in treating myeloma? What could some of the challenges be?
Dr. Costello: This has been one of the single most exciting treatments I have seen in my career. They were developing CAR Ts for other kinds of cancer patients and none of us really knew what to expect. But over the course of the last decade or so, we’ve learned so much.
CAR T stands for chimeric antigen receptor T-cell therapy. Your T cells are part of your immune system. They are these fighter cells that are designed to look for bad guys that come into your presence, whatever that may be.
What if there was an opportunity to train your T cells to specifically look for your myeloma? Speaking of personalized medicine, it doesn’t get much better than this. This is your own immune system fighting your own cancer.
Every myeloma cell has little tags on it that identify it as a myeloma cell. There’s a tag called BCMA, B-cell maturation antigen, on the myeloma cell. CAR T cell is a way that we can train your T cells to look for that tag.
The logistics of it can be a little overwhelming and it’s one of the challenges of CAR T. If you’ve ever undergone a stem cell transplant or have heard of it, it feels very similar.
Your T cells are removed from your body, similar to a blood donation. They’re sent off to a specific company that re-engineers them in order to create and train the T cell to look for that tag we talked about.
The CAR T cells are mailed back and, with some additional logistics, your doctor will put them right back into your body. Your immune system is now trained to look for your myeloma cells.
There are two different CAR Ts that were approved by the FDA in 2023 for treating relapsed or relapsed/refractory multiple myeloma. It’s approved for patients who have had four or more different treatments.
The benefit of it is that it is a one-and-done treatment. Myeloma patients have probably been on myeloma treatments for a very long time. They keep a lid on everything. Maybe it can delay it from coming back. But with that comes cost, time, side effects, and a lot of additional challenges.
When you receive CAR T-cell therapy, that is the treatment, and your immune system is now trained to go to war against your myeloma and knock everything down. It’s a very exciting opportunity to allow patients to have a treatment-free interval where they’ve done their treatment and can enjoy years without any additional therapy.
Unfortunately, it’s not curing everybody yet, but it’s buying us time, which is what we really do with myeloma treatments. We kick the can down the road until the next treatment comes.
There are lots of exciting benefits. With new drugs come new side effects that your doctor and you need to learn about and figure out how to manage to keep you safe. With new exciting options, there’s a lot of popularity around them.
There are a lot of logistics involved in getting the T cells out of you, engineering them, sending them back to you, having the manufacturing capabilities to do that, and that is time, money, and accessibility.
There is still not enough access for everybody who needs it to have it. We’re going to continue to fine-tune and hone this. But from what we’ve seen so far, it’s been a new, wonderful treatment option for myeloma patients.
Cindy: Patients were so excited when we had our first approved CAR T-cell therapy. It prolonged life. People who were out of options were given an option. That’s what we do in myeloma. We just keep on treating ’til the next new thing.
These CARTITUDE studies are looking to see if CAR T-cell therapy is at least as good, if not better, than our standards of care.
Dr. Caitlin Costello
CARTITUDE trials
Cindy: The CARTITUDE trials talked about cilta-cel or CARVYKTI. Can you talk a little bit about what we found out from the CARTITUDE trials and maybe specifically CARTITUDE-4 and what’s happening in CARTITUDE-5 and 6?
Dr. Costello: The CARTITUDE trials are looking at how can we use cilta-cel, which is one of the two CAR T products targeting BCMA.
Drugs get approved on the basis of safety and effectiveness from the very get-go. Truly, and maybe unfortunately, this is oftentimes studied with patients who have no other options.
Once we prove it works and that it is safe, then we can cast a wider net. If it works at that point in the disease, could we potentially study it in patients who have been diagnosed with myeloma more recently or have had fewer than four treatments or maybe even when they were first diagnosed?
The CARTITUDE trials, and there are a lot of them, are looking at exactly this. It’s a randomized trial that gives one set of patients the standard of care, what I know works, and another set of patients CAR T cells. These CARTITUDE studies are looking to see if CAR T-cell therapy is at least as good, if not better, than our standards of care.
We’ve been doing bone marrow transplants for a very long time and it has been great in the sense that it works. It has its issues, it has its side effects, and there are parts of it that are no fun. But everyone’s starting to say: can we compare that to CAR T instead?
We’re going to see more and more data coming out about some of these CARTITUDE studies. There’s the KarMMa study, which is evaluating the other BCMA CAR T cell with ide-cel, asking the age-old question: do we still need a transplant?
As a disclaimer, I’m a transplanter. I believe in transplants. Until someone shows me it’s better, there’s still a great role for transplant, but I can’t wait to see how those results turn out.
Cindy: I’m excited about that, too, because I haven’t had CAR T cell. I’ve had a transplant and from everyone I’ve talked to who’s had both, they had an easier time going through the CAR T-cell therapy.
The other more exciting thing is trying to put CAR T cells closer to the front line. As patients, we hear that sometimes CAR T cells aren’t working as great as they can because of exhausted T cells so if we did them sooner, they might not be exhausted. I’m hoping to see if that might be true and if we use some of these CAR T cell therapies upfront, maybe they’ll be closer to being curative than they are later on down the road.
The only way we’re going to find these answers is from clinical trials so we need them, we need patients to enroll in them, we need them to answer these questions, and we need those answers fast because patients are waiting.
We give an antibody that links the T cells to the myeloma cells. We are trying to engage the T cells so the T cells can act as the treatment for myeloma.
Dr. Carl Ola Landgren
Bispecific antibodies
Cindy: Bispecific antibodies are a new type of immunotherapy, too. Can you talk about what bispecific antibodies are, their mechanism of action, and some of the side effects that we’re seeing?
Dr. Landgren: From a development point of view, bispecific antibodies are very different from other antibodies. We talked about daratumumab and elotuzumab before they were developed back in 2015. The first bispecific antibody that came to myeloma was at the end of October 2022. We have additional two bispecifics in August 2023.
Bispecific antibodies bind to the surface of the myeloma cells and to the surface of T cells. They bring these two cells to sit next to each other. When a T cell sits next to the myeloma cell, it will kill the myeloma cell.
When we talk about CAR T-cell therapy, what does that mean? We take out the T cells, make them into CAR T cells, and those T cells bind to myeloma cells. You could say it’s very similar.
Instead of taking out the T cells, we keep the T cells in the body, but we give an antibody that links the T cells to the myeloma cells. We are trying to engage the T cells so the T cells can act as the treatment for myeloma.
The side effects of bispecific antibodies are quite similar to CAR T cells in that you could have cytokine release syndrome and these immune cell-mediated neurological syndromes with neurological side effects.
But usually with bispecific antibodies, you have less profound, less severe reactions. Most of the cytokine release syndrome we see are grade 1 or grade 2, but we very seldom or almost never see higher grades. But with CAR T cells, you could see grade 3 or grade 4.
There is some continued immunosuppression and patients seem to be more able to capture infections over time with bispecific antibodies.
Dr. Carl Ola Landgren
Cindy: Do bispecifics have higher rates of infection?
Dr. Landgren: Infections can happen both with CAR T cells and bispecific antibodies. I spent a lot of time going through the literature, trying to understand the dynamics of these types of immune cells and the side effects from both short- and long-term perspectives. I continuously go through the literature and talk to other investigators.
What I’ve seen is that the infections are more likely to happen earlier on with CAR T cells because you have more profound suppression. With the antibodies, the way they are developed is you keep on giving them. You not only hit the myeloma if it’s there or keep the myeloma away, but you also keep on hitting the immune system. You will see there is some continued immunosuppression and patients seem to be more able to capture infections over time with bispecific antibodies.
There are ways to prevent this and this all comes back to the physicians. Every time I talk about this, I always emphasize that doctors have to know exactly how to manage this.
These antibodies bind to markers, like BCMA and GPRC5D, which are widely expressed on myeloma cells. Unfortunately, these can be also expressed on normal plasma cells, which means that the patient would make fewer immunoglobulins. Low IgG in the body is called hypogammaglobulinemia and that could increase the risk for capturing infections. It could also be more severe infections.
A way to prevent these infections is to give intravenous immunoglobulin or IVIg. I always say to check your IgG levels. If they go under 400, you have to give IVIg. I would give it, check the next month, give it, and check the next month. If it goes into the normal range, then you can hold off, but you have to keep on checking it. If it starts drifting down again, you have to give it.
You can see with these combinations that you can bump up response rates from 60 to 70 to 80 to 90 to 95%.
Dr. Carl Ola Landgren
Cindy: The bispecifics that are currently approved are approved as monotherapy or just by themselves. There are some trials that are doing some combinations. Can you talk about those trials?
Dr. Landgren: The field is moving forward very fast and there is a whole range of combinations.
Damian Green of the Fred Hutch Cancer Center in Seattle found that myeloma cells can protect themselves by chopping off BCMA from their surface, the target for many of these bispecific antibodies and the currently available CAR T cells.
The drug binds to the target, but the target gets chopped off so it’s circulating free in the blood. The cancer cells are swimming by, waving to these receptors and the drug. That’s not a good scenario. How could you prevent that from happening?
Dr. Green and his colleagues found that this happens when the cells release γ (gamma) secretase. They used γ-secretase inhibition to stop this from happening. There are newer developments now and we have been part of this as well.
It’s probably overkill to give every patient this. For some patients, it may be the right thing to do, but in general, it’s probably not needed. That’s one line of investigation. We are not yet done, but that seems to be the way the field is going.
Then you could increase the efficacy of it. You could use other antibodies. You could use daratumumab in combination with bispecifics.
People have daratumumab and teclistamab. Let’s put them together and see what happens. People have used teclistamab with lenalidomide or elranatamab, which is also an approved BCMA bispecific antibody, together with lenalidomide and pomalidomide. You can start using it also with proteasome inhibitors, carfilzomib, or other drugs.
Why not take two of these bispecifics at the same time? You could take a BCMA and GPRC5D-targeted bispecific antibody and use that together. There is data coming out and ASH 2023 will present a lot of this data.
The bottom line is that these single drugs are amazing. About 60% of patients respond to bispecifics. To put it in context, when daratumumab was approved in 2015, it was 30%.
Patients today have been treated with many more drugs when they go on trials. Almost 10 years ago, there were virtually no drugs around. You could argue and say patients today are sicker than they were 10 years ago and it still delivers over 60% so that’s amazing.
You can see with these combinations that you can bump up response rates from 60 to 70 to 80 to 90 to 95%. There are some studies treating 28 patients and 27 of them respond. It makes me wonder how we can learn from that so we can take the last person over the goal line.
We will probably have, I would say, 95 to 100% response rates in later lines. These drugs will probably become part of front-line therapy. What we have known for a long time is that what works in later lines usually works better in earlier lines. If we have this discussion in five years, everything will have probably changed.
Cindy: Exciting times. I’m very, very hopeful. I hope to be here five years from now. When I was newly diagnosed, five years from now was really scary to me. Now with all these new drugs, I’m counting on being here and having a discussion with you in five years.
It scientifically makes sense for me to put CAR before BiTE, but I do think we have the reality of challenges with CAR T that don’t allow us to sequence it the way we would want to.
Dr. Caitlin Costello
Choosing Between CAR T-cell Therapy & Bispecific Antibodies
Cindy: How do I know whether or not I should be looking for a bispecific antibody or a CAR T-cell therapy? Dr. Costello, how do you have that discussion with your patients? I know it’s probably going to be very specific, but what are some of your guiding principles?
Dr. Costello: We have to break this down into the ideal world and the real world.
In an ideal world, everyone has access to everything. We are sitting in front of our patients, say A or B, and we can do A or B soon but that is not the real world.
The real world makes that difference for usually at least two reasons. People relapse differently. Some people have myeloma that grows back very slowly so we have time to organize the next treatment and think through the logistics. We can prepare ourselves or get on waitlists for CAR T because that’s the reality of CAR T.
However, other patients have myeloma that relapses very quickly. We may not have the benefit of time to think about our next steps, pursue treatments that may not be locally available, or be on a CAR T-cell therapy waitlist. We have to consider all these different scenarios to help make that decision.
In an ideal world, I like the idea of starting with CAR T. I would love for patients to have time to get off treatment and enjoy treatment-free intervals.
Bispecific therapies are a great way to keep using the immune system to keep pushing against the cancer cells, but they’re going to get tired, too.
If we continuously ask the immune system to fight, fight, fight, and then we try to take those immune system cells out and re-engineer them and ask them to go to a whole ’nother battle, they may not be as effective.
It scientifically makes sense for me to put CAR before BiTE, but I do think we have the reality of challenges with CAR T that don’t allow us to sequence it the way we would want to.
The other thing worth mentioning is that there’s this concept of a waiting period because we have different ways to attack the BCMA tag. As we attack it, we can see that the tag level in your bloodstream goes down as your myeloma gets killed.
At some point, it may regrow as your myeloma grows and we may need that BCMA to start growing back so we can attack it again. I don’t know if we know the answer yet about the ideal waiting period between doing sequential BCMA-targeted therapies, but it also does rationally make sense to me.
I think CAR T buys us more time to allow the T cells to do their thing then allow the BCMA to redevelop to allow us to target it again. It’s a little complicated because we don’t know.
No one really knows for sure. The jury is still out. There are so many questions that we don’t really have the answer to when it comes to this.
Dr. Carl Ola Landgren
Cindy: We could have a whole discussion on BCMA treatment, sequencing, and waiting periods. There’s so much going on.
Dr. Landgren: We talk about it at conferences. It always comes up and people talk about it internally. I get phone calls from private practice doctors asking for advice on how to think about it.
The short version is no one really knows for sure. The jury is still out. There are so many questions that we don’t really have the answer to when it comes to this.
If you look at the trials that use bispecific antibodies, some of those trials have allowed patients with prior exposure to BCMA-targeted therapies, like belantamab mafodotin or CAR T-cell therapy. If you look at the overall results, the numbers are not significantly different.
Similarly, there are CAR T cell studies that have been done that allowed people who have been exposed to prior BCMA-targeted therapy. Again, if you look at these response rates, they don’t look that different.
Based on the small numbers from available studies, if you do these so-called stratifications — you look at one study whether they have prior exposure or not, or do another study and flip it around from CAR T cell to bispecific or bispecific to CAR T cell — it doesn’t look that drastically different. There is no significant P value. There is no definitive answer. That’s why I started off by saying we really don’t know.
We have to be open-minded and we have to involve the patient. Every patient will have his or her own perspective.
Dr. Carl Ola Landgren
The Role of Stem Cell Transplant
Cindy: With all these newer treatment options, is a stem cell transplant still necessary?
Dr. Landgren: That is a very difficult question to answer because it is all about what you have as alternatives.
In a broader context, if you think about the whole world, transplant has been proven for a very long time. It was initially developed in 1983 for a very old treatment that is a spinoff of mustard gas, which is what melphalan is. It was mustard gas discovered taken in to become melphalan chemotherapy; that is the so-called transplant. It has been implemented around the world for all these years.
In many countries, there is limited access. There are very few treatment options for patients. Transplant remains a very, very good alternative. In many parts of the world, in 2023, this remains one of the most, if not the most, powerful therapies widely available so to take that away would be the wrong thing.
If you look at the United States, we are very lucky. We have so many treatment options. Is it the ultimate therapy for every patient? Do you have to have to do it? The answer is more complicated. It’s probably more towards maybe not.
If you ask someone who is a transplant specialist, that person will say, “It’s been around for a long time. I use it all the time. It’s a great therapy. It’s not a big deal. You should really do it.” I have respect for that and I see where they come from.
There are other people who will say, “There are so many new treatments. We have CAR T cells and bispecifics. There are so many alternatives. The patient is already MRD negative. Why don’t you keep the cells in the freezer and give the patient the option of doing a delayed transplant if needed?” I would agree with that, too. I have great respect for that opinion.
We have to be open-minded and we have to involve the patient. Every patient will have his or her own perspective.
Cindy: That’s why it’s so important to have educated patients who could be part of that conversation and make the decision about what they feel is best for them.
We don’t have a cure yet, but we can control the disease and provide a very good quality of life for many, many patients with these drugs.
Dr. Carl Ola Landgren
Final Takeaways
Cindy: Thank you all for such a wonderful and incredible discussion. If you had to leave our audience with one takeaway message, what would that be?
Dr. Costello: Advocate for yourself. There is so much that you need to understand about your cancer so that you can find your best, personalized pathway forward. With all these resources, you have no excuse to not do that.
Dr. Landgren: Myeloma is at a tipping point as a disease. If I put all my years of experience into perspective, it used to be a disease that was almost like a kiss of death. Now it’s a disease where the lifespan for many patients is getting very close to, if not identical, to the general population.
We don’t have a cure yet, but we can control the disease and provide a very good quality of life for many, many patients with these drugs.
Seek advice from experts. If you choose to be treated locally, the expert can always be looped in and give advice if there needs to be some changes and strategic considerations. Involve an expert when you’re newly diagnosed or if there are new decisions to be made. The future is very bright and we are always here to help you.
Cindy: I’m glad there’s a bright future. You just made this girl’s day because that’s not what I was told in 2008 so I’m glad times have changed.
Christen: I hope that you feel less intimidated by the clinical trial landscape and are encouraged to reach out to support teams like the Clinical Trial Support Center. We’re here to support you through your journey, whatever it may look like.
Cindy: It’s so important to be involved in your care. When I was newly diagnosed, I blindly followed my doctor’s orders. I grew up in that age of doctor knows best so whatever the doctor told me to do, that’s what I did without asking questions, without being part of that decision-making process. I’ve learned how it feels to be educated and empowered and part of that decision-making process.
Stephanie: Thank you so much, Cindy, for being our incredible patient advocate and moderator.
Thank you also to Drs. Landgren and Costello for the work that you do in the clinic and in research to help move the landscape of myeloma options and treatment forward, and for helping patients and families who are trying to navigate a multiple myeloma diagnosis and treatment.
Thank you to our LLS clinical trial nurse, Christen Hawthorne, for being there for people who are overwhelmed by approaching clinical trials.
We really hope that you walk away with a better understanding of clinical trials, specifically in multiple myeloma. Again, they may or may not be right for you, but our goal is to make sure you feel empowered to make a decision for yourself. We hope to see you at a future program.
Special thanks again to GSK for its support of our independent patient education content. The Patient Story retains full editorial control.
Tony’s Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) Story
Tony was in peak physical condition, working out several times a day when he suddenly began to struggle with fatigue.
After undergoing scans and tests, he was diagnosed with diffuse large B-cell lymphoma (DLBCL), the most common adult form of non-Hodgkin’s lymphoma. He would later learn that his specific subtype is known as T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL).
Before his diagnosis, Tony was an avid cyclist and fitness enthusiast. He noticed a decline in his physical performance despite his extensive training routine, as well as swelling in his leg. After consulting with his chiropractor and internal specialist, a CAT scan revealed that he had cancer.
Although his blood tests did not indicate lymphoma, the cancer had spread extensively throughout his body, leading his doctor to believe that he may have had it for years without knowing.
Tony made a conscious decision to keep a mindset of strength and perseverance that allowed him to face his diagnosis.
He voices how he processed his diagnosis, how he dealt with the side effects of R-CHOP chemotherapy and CAR T-cell therapy, and what he did to stay mentally and physically strong.
Thank you to Genmab & AbbVie for their support of our patient education program! The Patient Story retains full editorial control over all content.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Name: Tony W.
Diagnosis:
Relapsed T-cell/histiocyte-rich large B-cell lymphoma (THRBCL)
Initial Symptoms:
A lot of effort needed cycling; body wasn’t responding the same
I’m an igniter. I have started several businesses in my career.
I went to North Carolina State University and majored in civil engineering and pre-med. I wanted to be a doctor at some point.
I’m an avid cyclist. I love to work out.
I’m a go-getter. I can’t sit still. I like to initiate things and see things come to fruition.
I’ve always been that person that didn’t need someone else to motivate me. I’ve been highly self-motivated [throughout] my 51 years on this planet. I just love learning new things.
I play the organ, the bass guitar, [and] the saxophone. I love music. I sing [and] write music.
Anything that I put my mind to, I try to do the best that I can do.
My T-cell histiocyte-rich large B-cell lymphoma story
If you ask anyone who knows me, they would say, “No, not him. Can’t be Tony. No, you’re joking.” I lost a lot because COVID hit exactly at the same time. It was rampant when I got sick.
At the time, I had about 200 employees working for me. We lost a lot of contracts and things were just out of my hands. I couldn’t do anything about it because I had to focus 100% on my health.
Cancer doesn’t care [about] your economic background, what race you are. [or] your social status. When it comes for you, it will come for you no matter what you thought you had built up in life.
I thought I was leaving some legacy behind and it came for me. What am I going to do after it comes for me? I never asked myself why. I said, “Okay, why not?” And that was my approach. Why not?
I’m a guy that works hard, does a lot in the community, [and is] active in the church. There’s no discrimination. It can happen to anybody.
Pre-diagnosis
Initial symptoms
I’m an avid cyclist. We ride a lot of miles. At that point, I was doing about 350 miles a week. Being in an endurance sport, you learn [about] your body.
I have this reputation on the team of being pretty fast and pretty fit. I wasn’t giving the guys the business like I normally would be doing. It was just a lot of effort. Something wasn’t right.
They couldn’t really tell any difference because I just won’t stop. I give everything I have, but my body was not responding the same. If I wanted to go an extra five miles an hour, it was a struggle. Coming out the curb or the corner trying to chase somebody down was a struggle.
Then I started noticing that my leg was swelling. I lift weights a lot. I do spin class a lot. I said, “Maybe I hurt my back.” My chiropractor worked on it and she said, “This isn’t getting better. Your leg is swelling.” We thought it was sciatica nerve, but it wasn’t. She said, “Maybe you need to go see your internal specialist.”
I went to the internal specialist. We were thinking maybe I had kidney stones or something bacterial was causing me to experience this. When she checked me out, she said, “You look healthy. There’s nothing wrong. Your blood looks fine. But how about we just do a CAT scan?”
That’s when we had that “Oh my!” moment.
I was 49 going into 50 years old that year. I thought I was going to have this great 50th celebration. I was sitting in a chemo chair on my birthday.
When I first saw my oncologist, the first words that came out of his mouth [were], “If you were not as fit as you are, we would be having a different conversation.” All those miles, all that training, spin class, and gym work, whatever small percentage that was, gave me a jump start and it might have saved my life.
I’ve been an athlete all my life. You develop this push-through-no-matter-what mentality. We push past the threshold. That’s not a good thing all the time.
Think about professional athletes [and] collegiate athletes. Everybody pushes through but they pay for it [in] the end. That’s the mentality that you develop. No matter how you feel, you just push through.
“This hurts.” Push through. “I feel a sore here.” Push through. You develop that mentality that I’m going to beat whatever how I’m feeling and I’m going to still push through. That’s simply what I was doing.
Diagnosis
My blood wasn’t giving them anything. They would run my blood and it would come back good. No signs of lymphoma.
I look at it as if it was the perfect storm. If your body was going to operate in its most perfect form, my lymph nodes did exactly what they were supposed to do.
My cancer was so prevalent that my doctor thought I might have had it for years and didn’t even know it. It had completely taken over my stomach, my lung, everywhere.
I could see the fright in my doctor’s eyes when he saw [the scan], but he could see the tenacity in my eyes. When he told me what it was, [he went] over options.
I had to make a conscious decision. What are you going to do about it? There [wasn’t] any time for tears. I didn’t cry at all. I sat there and made a decision. I looked him in the face and said, “Okay, game on. Let’s go.”
I cried later but [at] that moment, I made a decision. I had to let the cancer in my body know: I’m not giving you victory in my mind this quickly.
I created this alternate reality. I created this warrior mentality. “You coming for me? I’m going to come for you.” No matter what my doctor said, I already told myself that [I’m] going to beat this. I’m going to do whatever I have to do to overcome this.
Breaking the news to family & friends
Initially, I didn’t let anyone know. I’m very methodical and I like to see things through before I bring attention to something. I want to have control of the situation. I wanted to know exactly what was happening because people are going to have a lot of questions.
Going through a chiropractor and my initial doctor locally and even once my oncologist told me, I still didn’t tell them about it. I waited.
I went for a walk. We have a pond in my neighborhood so I sat out there on the pond bench and that’s when I had my moment.
I called my mom. I’m the first child, the oldest grandchild. I remember telling my mom, “I don’t want to die.” She said, “What are you talking about?” I started crying and that’s when I told her.
My wife was there so she knew, but she was frightened. She didn’t know what to say or what to do. Then I told one of my best friends.
It hit me when I was talking to my mom. That’s the person that birthed me. It was devastating.
After that conversation, I zipped those tears up. I said, “It’s not a crying situation. It’s time to go. Time to go to work.”
Drawing boundaries
I said that I will not let family and friends imprint on me. We’re going through enough as is. We know our odds. We know the percentages. We know what we’re facing. Sometimes, [because of] their mere concern for you and all the emotions they bring to the situation, loved ones will compound your situation.
You have to put them at arm’s length. You can’t take on what they’re saying because sometimes, out of love, they will give you bad information or will remind you, “Only 1% of people live from this?” They don’t mean any harm but their words will hurt you.
This is what I did. Love your loved ones, but guard yourself. At the end of the day, it’s a one-on-one thing. You’re battling that cancer. You’re battling everything that comes with it. They’re not doing that with you. They will stand with you, but they’re not here. That’s where your battle is.
The crying was symbolic of accepting what was happening. It’s real. We can create all the alter egos we want, but accept that it’s real. The crying just released that in me.
I felt free. A freeness came over me. It was a calm and peace that came over me. I felt like it was necessary.
A lot of times, men are providers. We like to take care of things. We have our egos. We want to feel important. We validate ourselves by what we can do for you, what we can give you, or how we can protect you.
We’re not conditioned to be as emotional. Women are more emotional incubators and that’s a good thing because you need to have that balance. We need to have that also as men and sometimes we don’t. If you hold that in, [it’s] just adding more stress to your situation.
Crying and releasing helped me further along in my process versus me doing it at a time that wouldn’t be optimal. I was doing soul-searching, too. I thought, “Tony, you have done this. You came through this. You have broken through this ceiling. You have done all of these things. You can do that, too.” That’s how I approached it and it helped me.
Treatment
I had R-CHOP, which was pretty nasty.
I left my local doctor and went to [the] UNC hospital system. That’s where I met Dr. Boles, my oncologist. We talked about my treatment plan. He gave me all the options and encouraged me to get a second opinion.
But I already knew. When you know, you know.
When I look that man in the eyes, I see a caring, compassionate person [who’s] concerned for me. And that’s important because sometimes, a lot of us will get someone [who] doesn’t have [a] good bedside manner, just matter of fact, or [will] bring gloom to your situation and you already know it’s gloomy.
He talked to me almost like the big brother going to the little brother who’s a doctor. You’re putting your trust in the little brother now because he has [the] skill set you don’t have. That’s [the] kind of relationship he and I have. I was the big brother who was relying on him as my little brother to take care of me.
One thing he told me [was], “Tony, by nature, you’re not a selfish person. You employed people, started a cycling club, and you did all these things. You give a lot to people. But I need you to be selfish. This is the one time you will have to be the most selfish in your life.
“You have to block out all the background noise, all the chatter. Stay off of Google. Inundate yourself enough that you understand what’s going on with you, but don’t deep dive to the point that it causes hysteria.”
Keeping physically active during treatment
[During] certain rounds of my chemo, I was walking five miles a day every day and doing my spin trainer 30 minutes a day.
Finally, Dr. Boles said, “Tony, you got to pick one. You can’t keep doing both.” I already made a determination that I wasn’t going to let those chemicals run roughshod in my body and not do something about it.
I’m out there walking when I was feeling sick, made my other body systems kick in, and it made me feel better than just sitting there. Doing pushups gave me something to look forward to. It made me feel defiant. The more I became defiant, the more I start seeing victories.
Instead of losing weight, I was gaining weight. I was gaining muscle when I shouldn’t have been gaining muscle.
When I look sick, it affected everybody around me. They didn’t know how to handle me. They were very cautious because it was just so unnerving. Not only did I have cancer, which was evoking something in them, I now physically looked the part.
When I first got diagnosed, I got down to 167 pounds. I went to my doctor after chemo and one of my PAs said, “Tony, you’re losing too much weight.”
I basically starved cancer. I stopped eating bread [and] sugar. I only ate green greens like spinach and kale. I said, “I’m not giving you anything that you can live off of.” I was losing 6-7 pounds a week. She said, “You can’t do that. You’re losing way too much weight.”
The next time she saw me two weeks later, I was at 190 pounds. When she saw me the next week, I was at 205. I never stopped. I started doing pushups. I start physically challenging myself.
You don’t have to be that extreme, but I didn’t have anything else to do. I do believe that if you’re not physically fit or capable of that, do something. Don’t sit there. Show cancer that you will be defiant.
Dr. Boles told me, “Tony, one of my biggest challenges with my patients is me looking at them and saying, ‘Maybe just walk.’ But I’m looking at a person that never walked in their life so I have to be realistic and say if they weren’t walking before, it’s going to be hard for them to walk afterward. If everybody would just physically move their body, you’re going to move those processes along in your body.”
Chemo is designed to fight cancer, but it wreaks havoc on your organs. That’s a problem for a lot of people. I said to myself, “I need a healthy lung, I need a healthy spleen, I need a healthy heart,” and the only way I knew to keep those things active was to move. That’s what I chose to do.
I’m not trying to be anybody’s superhero. You have a baseline and then you have an extreme. All of us still want the same thing, to be cured and healed. I did, too. I chose the extreme. At the end of the day, we all want to get to the same place. Choose what motivates you to get to that place.
Side effects of R-CHOP chemotherapy
R-CHOP was funny. I’m just an enigma. Because I was doing those things, I’m just breaking all the rules.
I was going every 21 days. After my first R-CHOP session, Dr. Boles and the team would say “How are you feeling? You feel any chills?” No. “Sweats?” No. “Your hair? Well, obviously, your hair is not falling out.” Mm-mm. “You feel nauseous?” Nope.
I had no symptoms that first week. I really believe they didn’t believe me because he dragged me back in there right after the next R-CHOP session to test me. I didn’t feel anything. I was saying, “Oh, this is going to be easy.”
[The] second week, [I] got really sick. I was going into this pattern. [The] first week, I was good. [The] second week, didn’t feel so good. [The] third week, the light came on and I felt like I was back. That was my process all the way throughout like clockwork.
My body is responding pretty well. I had the Red Devil. I’m doing fine.
The right-hand side [of] my initial scan [was] what it looked like when I first walked into the door. A couple of weeks later, on the left side, was my scan after and that was a premature scan because he wanted to see what was going on. You could see how much of that cancer was eradicated just like that.
On my second round of R-CHOP, I see a bunch of needles. I said, “Whoa! Where are the bags?” They started giving me injections in the stomach.
Dr. Boles said, “You responded so well we’re going to go with some direct shots,” and they [were] putting half of my chemo directly in my stomach because I could handle it. That’s how strong my body was.
I have a port. I recommend getting a port because it saves your veins in the long run.
Hair loss from chemotherapy
Hair loss kicked in on my third session. I went to the bathroom, cut my hair, and it just start coming out in globs. It went just like that.
Your hair’s like your badge of honor. You take honor in that until you have that recessive gene and you lose it and can do nothing about it. But that hadn’t hit me so I still had mine.
You’re not going to get through this with no [side effects] at all and hair was one of them. To lose that, I felt like this is real. Cancer is still fighting. The chemo is doing what it’s supposed to do. It just was a reality check for me.
I would cover my head a lot. I didn’t like the bald look so I don’t have a lot of pictures from that. I don’t want to be reminded of that. I started wearing beanies and look more stylish, but there was no hair.
Savoring the small wins
When I started getting little stubble back, I felt good again. It’s funny how that works. You defeat it when you lose your hair, but when it starts growing back, you are so excited. Even if I didn’t have a lot of it, I was happy that it was coming back. It was like a victory.
It’s these small victories you have that you start thinking, I’m getting better. Cherish those moments because any moment that you can have and savor is a win for you.
Post-chemotherapy PET/CT scan
At the end of R-CHOP, Dr. Boles gave me a couple of months off. When I started feeling well, I jumped right back on the bike again. I was feeling good about myself. I thought, “Maybe we won.”
When I had that PET scan, he brought me back in and said, “Well…” I knew. He said, “We’ve got a couple of concerning areas.” I said, “Maybe they’re dead cells, just not giving up.” He said, “No, I don’t think so.”
At that point, I said, “Okay. I got to re-engage.” Dealing with cancer is a battle of engaging and re-engaging. For that brief month or two, I disengaged. But when he told me I had some trouble spots, I had to re-engage all over.
Relapse
Mentally, that was challenging. You have to have a counselor or someone to talk to. I started journaling and I would talk to myself a lot. I would talk to my body and my cells.
He said, “I’m going to send you to the big house, UNC Chapel Hill,” that’s where the teaching hospital is. “I’m going to send you to specialists there.”
He said, “I’ve taken you as far as I can take you, Tony.” [Do] you know how humbling that was to hear a man of his stature saying that? He’s pretty credible. He said, “I’ve got to send you somewhere else, someone that’s better than me.”
So impressed with UNC, so impressed with them. Again, he gave me options. I said, “You know what? The UNC family has been really good to me.”
When I met Dr. Grover, she was just like him. She was amazing. Later on, she said he told her, “When you meet Tony, he’s not going to look like you think he looks. He’s not going to respond like you think he’s going to respond. Just be ready because he’s going to be the opposite of anything that you’ve ever seen.”
CAR T-cell therapy
Early on, I had mentioned to Dr. Boles, “What about CAR T?” I had done a lot of research. He said, “That’s not available at the time,” cause it wasn’t available to my specific type so it wasn’t an option.
In December 2021, CAR T came online for my specific type. When I got to Dr. Grover, she said, “Tony, I have great news. You qualify for it,” so that’s what pushed us into CAR T.
I knew my body needs a break from chemo. That was not going to be an option.
I was very interested in CAR T from a scientific standpoint — taking your cells and modifying them to specifically attack cancer. That’s pretty ingenious.
Cancer is a very smart cell itself. It can change and evolve. Initially, your T cells will jump on it and eradicate it, but cancer will evolve and say, “We’re going to trick you. We’re going to change our makeup so you don’t recognize us,” so the T cells just come cruising right on by it and cancer can still proliferate. I thought it was interesting how they would reprogram ourselves to recognize the tip [of] the cancer.
I said, “This is if insurance would pay for it.” That’s the main thing. They said yes and that’s how we did CAR T. No other options. I wanted to do that one.
Doing research to help with treatment decisions
You have to do an honest assessment of how you’re feeling coming out of this. Chemo can be rough. If you feel like your body can’t handle that, seek second opinions. If your body’s telling you it can’t handle any more of this, it can’t. You may need a break if you can afford to have a break. But if there [are] other opportunities, make sure you understand what they are.
If you don’t feel right and you don’t feel good, you can’t continue down that path. You have to have time where your body can gather itself. That’s what I encourage more so than anything.
Understand your body and understand how much more of this you can take. Pay attention to what your levels are and how your organs are responding and that will tell you what your course of action should be. You have to make sure everything is at a place [where] it could handle another round or another series of chemo.
You have to ask yourself: how am I feeling physically? If your doctors say you’re at a point [where] we’re not as concerned with it spreading rapidly, pause a little bit just to get your mind and body back together so you can engage again. That’s what I would encourage, more so than what treatment you’re seeking.
Don’t be so quick to rush into one treatment, into the next, into the next because that degradation would take place in your body at some point.
Just the word practicing medicine is exactly what it is. It’s practice, unfortunately. They do the best they can through what they’re dealing with, their education, and what they’ve been exposed to, but it’s still practicing medicine.
Holistic care in conjunction with cancer treatment
I found a holistic doctor so I was doing holistic medicine in conjunction with chemo. I was researching holistic doctors in other countries that may not have the scientific approach as developed countries. Some of them rely on Mother Nature who provides us with everything that we need, too. I started looking at plants and herbs that can help me detox.
As quickly as you can detox chemo and chemicals out [of] your body, the more readily your body will be if you have to do it again. I was looking at different options to detox myself outside of traditional medicine.
You don’t want to just keep adding chemicals to your body. They give us chemo then they give us these other pills to help with this and that. But sometimes, Mother Nature gives you that and your body is readily absorbing that versus the tablet.
I would tell them what I’m taking because some of that may affect chemo. Chemo is strong and designed to do what it does. Sometimes you can alter how it works by taking some of these things.
Don’t be a renegade. Do these things in conjunction. Make sure you let them know what you’re taking and then they can tell you. Some things he would say, “I don’t recommend that,” then he will tell me why and it would make sense. Seek other opinions but also validate that versus what you’re already doing. You got to have that balance.
When I would throw all these things at him and he didn’t dismiss me, that’s when I knew he was the doctor for me. Your physician and your team matter. You have to feel good about them. If you don’t feel good about them, find someone that you do. They affect everything about your situation.
If you don’t feel loved or feel like they care, then with the treatment that they’re giving you, you’re not going to have confidence in that. Make sure you feel good about them.
Preparing for CAR T-cell therapy
CAR T was my most difficult time simply because I was just so uncertain. I was saying to myself, “Okay, I went through R-CHOP. What if CAR T doesn’t work? What’s better than that?” For a moment, my mind would go dancing.
The chemo depletion was very hard for me. They take you to the edge. I had three days worth of chemo depletion.
When you’re sitting there, you can be full of life and your eyes could be all bright and bubbly. But when that chemo starts coursing through your veins, it’s almost like a dimness comes over your body and you can feel an extraction of life just coming out of you. It’s like getting close to death.
Chemo depletion is exactly how it sounds. They depleted my body to the point that there was nothing [so] that it would accept those CAR T cells.
The first day hit me so hard. I went through six rounds of R-CHOP and I didn’t feel like that because they would always give me something to try to bring me back. They would give me the white blood cell shot and help me boost myself back. But this time, [there] was none of that. I could feel like my essence leaving me after that first day.
You had to be within 15 minutes of the hospital. I live an hour and something away so I had to move up there. I stayed in a SECU House, which is like a Ronald McDonald House for grown-ups.
They took me through the back entrances of the hospital to get to the CAR T center because you had to be away from people. You had no immune system at that point.
I always would pass the chapel going up. [On] the second day, I went in and broke down crying. I said, “Lord, I can’t do this.” It drained me so bad I felt like I couldn’t do anymore.
I sat in that chapel [for] about 5-10 minutes. Then I got up, dried my tears, sat in that chair, and had my second day. I did the same thing [on] the third day.
I stayed at the SECU House and started my rehab and recovery. The people there were great. They cook for you, you meet other cancer patients in [the] same situation, and you realize that there [are] a lot of people in worse situations than you.
Nurses call me Zeus at the hospital. At the SECU House, I saw people fighting for their life and I’m walking around like I’m going to a training camp somewhere.
Typically, you have to be there [for] 30 days depending on how you respond and you have to go to the hospital every day for labs. [In] my first seven days, I had no symptoms. I was feeling great.
I was sitting there talking to my CAR T cells and said, “You guys are my special forces.” Every night, every day, I would check in with them and say, “Hey, what [are] you guys doing?” They’ll say, “Executing. Executing, boss.”
I would talk to myself like that literally. I thought, “Execute. Go into the highway and the byways in my body and find cancer and kill it.” I was just talking to my body.
After the seventh day, my head nurse said, “You’re doing so well. We’re going to let you go home.” This was a Wednesday. That Friday, I got super sick, wound back [in] the hospital, and stayed for 10 days. My doctor was joking, she said, “You [were] my little superstar and you wound up back in here.”
I didn’t have any other side effects. I was lethargic for a while. The fever was the only thing that showed up. After they determined how to get that down and I actually broke it, they let me go back home and I’ve been home ever since.
Post-treatment scan
I finished the CAR T in December 2022 and had another PET scan [in] January 2023.
We found some cells, but I told Dr. Grover the same thing. I said, “Maybe they’re dead.” She was the same way, “I don’t think so.”
I was very discouraged because I put a lot of faith in the process. But all hope wasn’t lost because we were unsure.
The spot that I still had resonating was in the original area. It was very difficult to get to so she wanted to do a biopsy. They went through my hip to get to it. They took 16 to 18 samples and they were decent samples that we could tell what’s what.
Miracle moment
If you believe in miracles, I would say this is a miracle moment. When I met with Dr. Grover [about] the results, she said, “Tony, it looked like someone had pinched it.”
If you can imagine pinching your cell, smashing it, and just excreting everything in it, like you squeezing something really, really tight, that’s how that cell looked. She said, “The report said no lymphoma found.” I thought, “That’s a miracle, right? That’s a miracle.”
But doctors don’t deal in those terms so they’re not going to say certain things. They’re not going to give you certainty or anything because they don’t know. But we both were smiling. No lymphoma found. It was inconclusive.
I have another PET scan to prove whether or not those cells were active, dead, or whatever they were. We will know more.
I had another moment of victory. Typically, when they give you that report, it’s a whole page. When the radiologist gave the report, it was only five lines. That’s all he said. It looked like this and no lymphoma found so that was a win for me.
At that moment, I didn’t want to talk about the what-ifs because now, my faith is renewed again. I’m engaged.
I’m telling myself, “When we have this next PET scan, it’s going to reinforce what we already thought. Those cells are going to be dead.” That’s what I’m saying to myself.
Now, what if it’s still there, right? But it’s the same what-if that we had before. We never did targeted radiation, stem cell transplant is still on the table… A whole lot of stuff is on the table because of how my body responded. My organs are super healthy so they feel confident that I could withstand something if we had to.
I ask my body to respond every time I get knocked down. I think that’s just my faith. That’s the promise that I believe, that I hold on to.
A lot of times, it [doesn’t] have to make sense to a lot of people. It just has to make sense to you because that’s what’s keeping you going. If you’re putting your faith in that, that’s what’s keeping you going. I don’t care what nobody else thinks. Eliminate the background noise.
Words of advice
You have to cry. Go somewhere alone. I was alone, out in nature, crying, [and] talking to my mom. You can’t do that amongst other people. There are moments for that.
You need to have that alone time so you can get yourself prepared for what’s to come. It’s going to help you because it makes them stronger.
Listen to what your body is telling you
Get checked. Do your yearly checkups. Go beyond that. Get your blood analysis done. Take more control of your health.
Sometimes if you feel pain, it’s for a reason. Just go get checked out. I was one of those ones that, “I don’t need to go do that. I know what to do. I’m just going to put some ice on it. I’m going to get a massage. I’m going to do this.”
Go get checked because sometimes, there are things going on in your body that you can’t see that need to get checked. For all the athletes, for mom and dad sitting on the couch, your kids, get checked out and go a little further.
Sometimes the basic check is not enough. Add extra to that. Get your prostate checked if you’re a man. Get [a] mammogram if you’re a woman. Get the blood test done so you can see what’s going on in your body. Those things matter. I would definitely do that over because I didn’t do a great job of that at all.
Make the most of your hospital stay
I made a lot of friends in the hospital. Try to make the most out of it. The nurses and I would have fun. I used to tease them all the time.
You would think, I’m here for my care. They’re giving me chemo. They’re taking care of me. Then they ask you if you’re hungry and they give you some cookies. Like, “What? Cookies? Where [are] the oranges and apples?” They give you all this stuff that you shouldn’t be eating.
I had a good time. I bonded with my team doing R-CHOP. I am thankful for every nurse because they are doing God’s work. It goes unappreciated [and] devalued sometimes, but they work long hours and they legitimately care for you.
That is your frontline. You’re not going to see your oncologist in there with you. You’re going to see the nurse and you’re going to see them all the way through the end. Don’t be nasty and bad to your nurses. Love them. Encourage them.
I would do little things for them just to give them a ray of cheer because they’re taking care of me and they’re breathing life into my situation. They’re making sure I’m taken care of and I appreciate that. You got to appreciate that.
Cancer is bigger than you
This is bigger than you. Why are you in it? It’s not all about you. It’s bigger than us. When you help other people and pour into other people, it will come back to you. The more you give, the more you will receive.
You have to be selfish to protect yourself while you’re going through this, but you also have to accept that maybe [you] can help somebody. Maybe I can do something. Maybe I can [make] a difference in somebody else’s life while they’re going through this. Maybe I can volunteer at the cancer ward.
Keep yourself engaged not so much on your situation but think about someone who’s doing worse than you.
My biggest impact was when I stayed at the SECU House and I saw so many people that were worse than me; that encouraged me. People that could barely move were cooking breakfast for us, making lunch and dinner for us. They were giving back. In spite of their situation and no matter how they felt, they were willing to give back.
I said, “My life will not be the same. I’m going to give back. I can’t wait till I get some clearance runway.” We’re at the hospital a lot dealing with this. I can’t wait till my doctor says, “You don’t have to come as often. We’ll do it every quarter.” That gives me more time to get activated and start doing stuff because people need that.
Have faith
Sometimes, you just take [the] faith that you have. Faith is something that you really can’t see, so you’ve got to put it in something. Either you’re going to believe in a doctor or you’re going to rely on your faith in God. I chose to rely on that and held on to that
As a result, every time I get low [and] feel like I can’t make it, I just recall that. I’m hoping and believing in the outcome that I want to see happen.
I encourage everybody [to] grab faith and believe because that’s where the battle starts. It starts right [in the mind]. Physically, you can do all you can, but if you lose the battle [in the mind from] the very beginning, you’re fighting an uphill battle. Now you’re battling your belief that you can even be healed from this or that you can be cured from this.
When you can look beyond your situation and into somebody else’s life and try to help them, it will help your situation. It’s that faith — believing in something strong enough that you know the outcome of this end will be for you.
My wing is being fixed so I can fix somebody else’s wing and say, “You know what? At one point in time, I had a broken wing, too.”
We have our tribe. When we move and make an assault on this, together is so much better than going lone wolf. You got an army behind you so it’s not over.
Stay steadfast, everybody. It may seem difficult. It may seem bleak at times, but stay steadfast. Don’t let outside sources influence you. Stay steadfast even in your darkest moments.
Listen to The Patient Story. That’s what I did. One of my favorite stories was Nina. Those are the things that get you by.
We all have our faith, but sometimes you got to put your hands on something. You have to put your eyes on something so guard what you see [and] protect what you hear.
Special thanks again to Genmab & AbbVie for their support of our independent patient education content. The Patient Story retains full editorial control.
Cathy was diagnosed with myelofibrosis after a routine blood test.
After her husband retired, she encouraged him to do a blood test with her to get a sense of their health status. Her husband’s blood test results turned out normal while hers showed a low platelet count and teardrop-shaped red blood cells.
She later got a spleen ultrasound, which revealed a slightly enlarged spleen measuring 18 cm, and a bone marrow biopsy, which revealed myelofibrosis. Her myelofibrosis story includes a stem cell transplant, clinical trials, support groups and GvHD.
In addition to Cathy’s narrative, The Patient Story offers a diverse collection of MPN stories. These empowering stories provide real-life experiences, valuable insights, and perspectives on symptoms, diagnosis, and treatment options for cancer.
I’m originally from Shanghai. I came to the US in 1990.
I’m married with a 19-year-old son and a 32-year-old stepdaughter who lives in L.A.
I worked in insurance for the last 19 years. My husband and I both did, but he did for a lot longer. I was a product manager and worked on the IT side, making sure my business had a robust and stable system.
I like running outdoors, working out, and doing weights.
Pre-diagnosis
Routine blood work
When my husband retired, I said, “Let’s go get a blood test,” because he doesn’t like to know about those numbers. His numbers came back all normal and mine was pretty much all normal except for the platelet, which was in the 50s. I didn’t understand it. I know it’s lower than the lower limit.
A couple of days later, my primary care physician from Kaiser emailed me, and said, “I want you to get a spleen ultrasound.” I wondered why. I did the ultrasound and my spleen is 18 cm. Then that’s when I started Googling and found out that 18 cm is 50% larger than normal so there must be something wrong with me.
I Googled it right away. What’s the purpose of a spleen ultrasound and what happens if it’s a certain size? I have a general idea why before I went in and when I got the result, it just confirmed my suspicion that it had something to do with a blood disorder.
A couple of days more, my doctor said, “You have teardrop-shaped red blood cells. Now you need to get a bone marrow biopsy.” I searched YouTube videos and saw the big needle with the big handle drilling in. I asked, “Do I really need to? Is there another option?” She said, “That’s pretty much the gold standard.” I thought, Gold standard for what?
I was nervous about the procedure itself, but it wasn’t as bad as I thought. They did have a little trouble getting the marrow out. Later, I found out it was actually a symptom because I’m kind of dry.
Reaction to the diagnostic procedures
I was more anxious. I’m the type of person who likes to know all the details and I felt I wasn’t fed every detail. From the teardrop-shaped red blood cell, it pointed me in the same direction as well. I’m already thinking, I think this is it, but I’m not sure, and going back and forth.
How detailed did you get in your research?
I saw primary myelofibrosis as one potential diagnosis.
I don’t feel like I have cancer. Other than I have quite a bit of a strange bruising on me, which is normal because I’m clumsy, but those are in areas that I don’t usually hit myself with like the back of my finger. I still feel normal.
On one hand, I thought, Maybe the numbers are pointing in that direction. On the other hand, I just don’t want to believe it. Maybe something is wrong.
Around late April, I had quite an episode of vertigo. Never happened to me before. I was driving home, probably 10 minutes away, when all of a sudden, I felt blood traveling from my left ear to the brain. It’s almost like I can hear it. Then my vision became blurry. I thought it was my contact lenses getting dry. I kept driving for a couple of blocks and the road just started moving. That’s when I got a little scared. I parked on the side of the street and closed my eyes. I couldn’t open my eyes. I called my husband to pick me up.
We went to the ER. They couldn’t find anything. I had a similar mini-episode about ten times for the next 2 or 3 weeks. I know when it’s coming. The noise comes then my head spins. If I keep my eyes closed, I’m okay.
I later read that it may have something to do with low platelets but I don’t hear too many people mention that. I didn’t make the connection until later on.
I still run and do weights. I work during Eastern time so I get off at 4 o’clock. I get really sleepy. I don’t usually take a nap in the afternoon but I would nap on the sofa for an hour and have him wake me up so I don’t sleep through dinner. That’s in the last month or two before the diagnosis.
Being referred to a hematologist
I’m the type of person who worries about a lot of small symptoms. I would email my PCP and she’d tell me if this is something to worry about. But this time, she acted very fast.
Three days after my blood test, I went back and looked at the history of our emails. She asked me to do the spleen ultrasound. A couple of days later, teardrop-shaped red blood cells. She said, “Read this.” In the paragraph, it already said leaning towards MPN and I had no idea what MPN is. Probably a week later, she said, “I’m going to refer you to a hematologist,” and that’s when my hematologist and I spoke.
Appointment with the hematologist
I think he had a hunch. My husband was listening to the call as well and I can tell he was trying to be very conservative. He asked me about my symptoms and was trying to gather information. Then he asked, “Do you have a sibling?” That was another clue for me.
He said, “I need a few blood tests.” He didn’t get into detail. I asked, “Am I going to get a chromosome test?” He said yes because I knew about the list of tests. I just want to make sure I’m getting all my tests.
As soon as I met my doctor, he said, “Don’t Google.” I’ll say the opposite but with a grain of salt. How would I be able to ask these questions or know what’s missing without knowing what tests pertain to my disease?
You have to look at reputable sites. I go to the Mayo Clinic and the American Society of Hematology. They’re hard to understand. I look at the article as if they’re a foreign language. I Google pretty much every word to understand.
I figured that it’s a disease so someone has to be able to understand it, no matter how complex. It boils down to something is wrong with you that’s causing this and therefore there’s a potential solution.
Diagnosis
How long did it take to get a diagnosis?
A month. It was the longest month.
During work, I was busy enough not to think about it. As soon as work was over, my brain just gravitated toward, “Could it be cancer? Could it be something else? What’s going to happen?”
I already looked at the life expectancy, but I didn’t know how severe I was. I did not find out about the scoring system so I don’t know how to score myself yet. What’s going to happen?
My son is 19. If I’m not here, financially, he will be okay. I planned this from when he was very young. But what if he needs guidance?
Who’s going to take care of my husband when he needs medical care? He is a lot older than me. How about my parents?
Eventually, my brain got really tired. I didn’t want to think about it anymore.
Getting the official diagnosis
I got the call with the diagnosis on July 8th. I remember when we had the call. Now, I think back, Would it have been better if it was in person or through video?
As soon as we got on the call, I could sense he was nervous. He wanted to be careful how to break the news to me. I told him, “I’ve already done my homework. I think this is what I have and if that’s the case, go ahead and tell me. I’d much rather know about it and get it over with.”
He explained the scoring system, my platelets, spleen size, and fibrosis. Mutation-wise, I’m okay.
As soon as we got off the call, I was Googling MIPSS70. Now it makes sense, but at the time, I didn’t know about it. All I know is I’m probably MF-3 but what that meant, I didn’t know.
Joining online support groups
Some are much more experienced. Some can read my bone marrow biopsy and tell me whether it’s good or bad because I couldn’t understand some of the terminologies. But a lot of time, people give you support and prayers, which are helpful, too.
Myelofibrosis scoring system
There are actually multiple scoring systems. China uses a slightly different scoring system, which doesn’t take into consideration the genetic mutation and the karyotype, which puts a person that potentially could be high risk into medium risk, which changes their life expectancy.
That was actually something I was trying to show in my Chinese group. The website is in English. People can actually click on the link and translate to Chinese. However, the algorithm stops working; it won’t do the addition for them, but it’s good to spread the word out there. You also want to look at those two as well, not just your blood count or your fibrosis level.
JAK2 gene mutation
JAK2 was my mutation type. I don’t remember what that karyotype was, but it was a deletion of one of the 44. That’s the part I don’t remember. But in the scoring system, it will tell you these are the bad ones so I fit into one of those.
Reaction to the cancer diagnosis
I wasn’t sure where the scoring system came from. I thought I’d done enough research. At first, I didn’t believe in the scoring system. But then when I started looking into it, I realized that they make sense and they’re very objective.
It’s either you have a platelet below a certain number or not, or you have this mutation or not. It’s black and white. Before this, I couldn’t tell. It’s just that I wasn’t prepared to have this number thrown at me.
Talking about the diagnosis with the family
My husband doesn’t talk much when it comes to this. I know he was trying to be very calm for me. He always said, “Maybe there’s a treatment out there. Maybe there’s hope.” He’s always trying to give me hope.
He likes to keep things to himself and I like to get it out of him so that’s our conversation. I would talk about my concerns and he doesn’t talk much.
My son, being a teenager, doesn’t talk much, but he occasionally would ask me or even his stepsister, “What’s going to happen to my mom? How many years can she live? Is it going to get bad very soon?”
You can tell he’s thinking about it, but he’s probably not comfortable coming up to me to talk. I wanted him to know right away because I think he’s old enough. I don’t want to hide this away from him.
Feeling healthy but knowing something was wrong
It was very hard. I was hoping to get a second opinion outside of Kaiser, but because it’s HMO, it’s different.
I was able to get a second opinion from a different hematologist within the Kaiser network. He took his time, looked through my numbers, and concurred with the diagnosis. I also reached out to four hospitals outside of Kaiser, some major cancer centers.
In our Facebook group, we always talked about MPN specialists. In my experience, it’s actually not that easy to get ahold of one.
My Kaiser hematologist isn’t an MPN specialist but his diagnosis was accurate. He said, “We handle one myelofibrosis patient each month,” but I didn’t know how to interpret that. Looking back, it’s probably a pretty significant number because Stanford handles about 25 myelofibrosis transplants a year.
Out of the four major hospitals, one of them got back to me. I can talk to a hematologist but not an MPN specialist and it will total about $5,000 out of pocket.
Understanding fibrosis
When your level is high, even after you’ve gone through a transplant, the fibrosis level is not going to decrease right away. It might take months before your fibrosis levels go down, which means your blood count may not go up as fast as other diseases so just be prepared.
One thing that I hear most commonly is, “Is there a drug out there that could shrink my spleen without lowering my blood count too much?” A lot of the time, by the time your spleen is enlarged, your blood count is already borderline. You’re getting close to being transfusion-dependent.
They’re all related to each other. When your fibrosis is high, your bone marrow is not making as much blood, therefore, your spleen is working extra hard to make up for it.
Some patients have spleens that are much bigger than mine and they couldn’t find a solution to reduce it. I feel bad for those patients because their spleen needs to be shrunken enough to get a transplant. I’m lucky enough that mine was just slightly enlarged. Some are 24 cm. Mine was 18.
He said that I might want to consider a transplant in the near future. I said, “Oh, that’s why you asked me about siblings last time.” He said, “You may not need it right away, but it’s better to consider when you’re still relatively healthy.”
He spoke very slowly just to make sure I could digest everything. I think he said I had at least 1 to 2 years. Maybe it’s five years because I didn’t feel that bad.
I didn’t digest it at that moment. I’m kind of a dinosaur when it comes to this kind of thing, but eventually, it kicks in.
I’m not too worried about dying myself, for some reason. I’m just worried about leaving people behind. What can I do now for these people? I don’t know why. It just never dawned on me. It’s not scary for me to die, but it’s scary to leave people behind.
Stem cell transplant
I pushed for the transplant. When I went in for my first appointment with the Stanford transplant doctor, after the discussion, I said, “I’m ready. Just give me a date.”
When I got the date, October 1st, I did a lot of preparation beforehand and even imagined what my room would look like.
I love the nurses there. I had about at least 15. I met 15 nurses because you have a morning shift and a night shift. I learned so much from just talking to the nurses. Why do we do this? Why is this way? Why does the chemo nurse have to wear another gown and there’s always another nurse there just to make sure I’m getting the right chemo?
They kind of became my family during those 23 days because my husband doesn’t talk much. He would spend a whole day sitting in the room with me, keeping me company, but we didn’t talk much. But when the nurse comes in, we talk, even in the middle of the night. I thought I would not have much sleep. I wake up every few hours, but I just went right back to sleep.
I started fludarabine on October 1st. I had four days of fludarabine followed by melphalan; that’s the day we need to chew ice. Forty-five minutes before, I was getting cups of ice chips from the nurse, chewing non-stop all the way through then 30 minutes after. No mouth sores at all throughout the process.
On day zero, I started to feel tired. On days one and two, barely ate, but I had fruits. The next few days, my husband pushed me to get up, walk around, and take a shower. We were supposed to walk around half an hour a day. There’s this pink mask that we wear when we go to the hallway, which makes it harder to breathe. But if I exercise in the room, then I don’t need to wear it.
I danced with my IV pole. I like dancing, but he is not into dancing so I danced with my IV pole because then I can grab the pole with me wherever I want to go. It was really fun because we played music. That was one of my exercises. I even brought in my 8-lb weight at some point so I did some weights, too, because I know I’m going to lose muscle.
Side effects of stem cell transplant
Overall, the experience was a lot smoother than I imagined.
I thought I would have a reaction to the chemo right away, but it wasn’t until 5 or 10 days after that my body started to feel them.
One way to describe the initial feeling of chemo was kind of like towards the end of pregnancy when your body is getting heavier and heavier. It’s harder to do basic stuff. Going to the bathroom takes a lot of energy. Taking a shower requires two people.
Then comes the nausea and diarrhea, but they can be controlled. What I found out later was ondansetron works for me. It doesn’t work for all patients. One of the nurses said I could have it every eight hours so I never feel the nausea and I’m ahead of the game. As soon as that happened, I was able to eat a lot more than before.
Possibility of graft-versus-host disease (GvHD)
I think age makes a difference. My brother being a full match made a total difference. Once I got my diagnosis, the first thing I did was call him. He was in China. I said, “I need you to go get an HLA typing done. I don’t want to wait for the doctor to send you the kit,” so he did and the results came back very fast.
Looking at the typing, it’s so easy to understand. They look like 12 sets of timestamps. You compare one against the other. If you match, you match. I didn’t think he would be a match because we have different blood types. He was 12 out of 12. Full match.
After that, he said, “Let me know when you can get your transplant scheduled. I need to buy the airplane ticket.” At the time, China was still on lockdown due to COVID. He lives in Shenzhen across from Hong Kong; that city was locked down so we were worried he could not leave. Fortunately, right before his departure, it opened up.
It was better than winning the lottery.You can’t buy a perfect donor match, especially one who’s related. It would be nice to win the lottery, too. But when you’re in that situation, this is definitely better because the lottery can’t save a life.
For the first three months, I was supposed to be hiding away upstairs. I didn’t completely follow that because I felt okay. I was weak. When I went upstairs, I felt my legs were heavy. I thought maybe I could use going up and down the stairs as an exercise to gain strength.
I was hungry all the time so at midnight, I would be eating mini saltine crackers. My husband said I sounded like a little mouse in the bedroom. At four o’clock, I’ll be hungry and crave traditional Chinese food. I would be cooking rice soup and steamed pao at 4 o’clock. He doesn’t know how to cook those.
For four or five meals a day for about a month or two, I ate whatever I wanted to eat and did not gain weight. That was probably the only time in my adult life I would not gain weight eating like that.
For the first three months, I went back to Stanford ITA once every three days to check my blood. I needed a transfusion a couple of times. After that, I was fine and they just checked if I needed any adjustment on my medication.
They want to make sure because, during those first three months, you could have acute GvHD. Your blood count can fluctuate quite a bit.
Advances in research & treatment options
I actually met a lot of patients who aren’t the best candidates for a transplant. There are definitely medications to bring up their platelet or their red blood cell count. I actually talked to a lot of families of patients like that.
There’s not a whole lot that can be done. A lot of times, the patients themselves are not optimistic about what could happen to them. It’s really hard for their families to get them to a different state unless the patients are ready to deal with it.
Follow-up protocol
Istill go in for follow-ups once a month. Probably at least for another year.
Community support
Importance of finding support in a community
I met a 71-year-old patient. She arrived at Stanford two weeks after me and had some complications. She ended up having to go back there and was actually hospitalized. One day, I met her in ITA and it’s like a reunion. It felt good to see someone who’s been through it with you.
That’s the reason why I started to blog online with hashtags specific to myelofibrosis. A lot of patients chime in. They know what I went through.
Sometimes they ask for my opinion or my suggestions. I didn’t post on a site where all my friends were because I didn’t want them to feel uncomfortable not knowing how to talk to me about this. I know some did get uncomfortable when they eventually found out. I don’t want to impose on them by doing that.
Supporting patients with different backgrounds
China has a very different dynamic. Patient-doctor relationships are a little different. A lot of times, patients are afraid to ask the doctor questions so they actually help each other.
The patient actually knows more about the disease than a lot of the patients here. Give them a bone marrow biopsy report and one person can look at the different numbers and decipher it for you.
The treatment options are slightly different. The philosophies are different there, too. China seems to believe in MAC approach versus the reduced intensity (RIC) approach. They want to clear all your marrows, make sure there are no bad cells in there, and then bring in the stem cell. But here, studies show that the reduced intensity produced just as good as a result.
As a result, when patients go through MAC, there is a lot of damage to their organs. They are in the hospital for two weeks of chemo and they have much stricter diet restrictions. I felt that slowed down the recovery.
There was actually one patient I met who was going through a myelofibrosis stem cell transplant. It’s very hard to find a full match for Asians. He couldn’t find any good match. I got lucky because my brother is a full match.
His two sisters flew in from China; they’re not good candidates. I think he ended up using his daughter, which is very rare. It’s very rare to use kids but the daughter pulled through. He’s going through a haploidentical transplant, which is a little harder. I think it’s a lot harder than mine because there’s more chemo involved to reduce GvHD. He had days of fever.
I message him sometimes. I message other patients as well or they message me. There are a couple that are about to go into transplant at Stanford. I want to share my experience and I want them to benefit from mine as much as they can.
Words of advice
Knowledge is power. There’s a lot of information that’s not valid. You just have to figure out which one pertains to you. Use information from Facebook groups because some of these patients did go through the transplant so they can validate one way or the other.
A lot of times they say you don’t need to know about it and just let the doctor take care of you, but you also need to be able to make calls. Is this treatment for me?
For example, when I was given the initial chemo protocol, it was part of a clinical trial with T-cell depletion, which doesn’t make sense for a full donor match so I questioned that and then it was changed to a different protocol. I’m not saying not to trust the doctors, but I think there’s a reason they put you in one versus the other. Do your homework. Make your own call.
Clyde’s Caregiver Story
What do you remember from the first time you saw Cathy?
We were both employed by the same company. I sized her up as being a very quiet, introverted, typical Asian lady, which she was. It turned out that once you get to know her, she’s a very assertive, intelligent person with a mind of her own. We started dating about two years after she started working there. It was only then that I found out she was very assertive.
What do you like doing together?
There’s a 17-year age difference between us. There’s a cultural difference so there’s not a whole lot that we have together in common.
She likes to dance; I like to sit by the wayside. She likes to eat Chinese food; I like to eat Mexican food. Our life has been a series of compromises more than anything else.
We like to do a little bit of cooking together. We like to help out with non-profit organizations. We went to Mexico once to build a house with our school church group, but age prohibited me from doing it again. Cathy and her son Tom made a second trip down there in 2022 to help build a house.
It’s a very satisfying experience and I would encourage other people to go and do it. It allows them to see how people who are not so fortunate live. They don’t have running water, they don’t have electricity, they don’t have flush toilets, or anything else.
Reaction to Cathy’s blood test results
My personality is not to be the knee-jerk, oh-my-gosh type of reaction. We’ve got something here that’s not very normal. Let’s just see where this goes first. I had a little bit of time to process.
For the next day or two, I was thinking, It could be absolutely nothing or it could be something a little bit more serious. As time rolled on and we did more and more tests, it became very obvious that this wasn’t something that was just going to be simple. It was something that was serious.
Later on, I realized that it was something that was extremely life-threatening. It hit me a little bit slower than it hit Cathy.
I think Cathy is the type of person to look at it and say, “Okay, I know exactly where this is going.” Maybe she’s a little bit too over the top; that’s her personality and for this situation, it worked out best for her.
Understanding myelofibrosis
Cathy is the type of person to do a lot of the research. As she was doing the research, she would tell me what was going on and then I would slowly process it, but there really wasn’t anything else that I could do.
I’d talk to her every once in a while, figure out where she’s going with this, learning what she learned because she’s a very good learner at this. I’m a very slow learner so I’d have to ask her question after question after question before it would sink in.
Impact of a life-threatening disease
I couldn’t fathom it. I couldn’t fathom losing my wife. She’s a lot younger than I am and it was just racing through my head that this isn’t fair. I should be the one that should go first. I was just so afraid that I’d lose her. That was the hardest thing for me to process.
Once I got over that, I realized that we weren’t throwing in the towel. Not now, not when we still have options. She’s a strong lady. She was going to deal with it.
Because we’re a team, we’re going to see this thing through together. I’m going to be there every step of the way. I’m going to give her encouragement and we’re going to fight this together.
I had a pretty good feeling that we were going to beat this. I say we because it is her and me. As a caregiver, maybe you’re not doing the actual fighting, but you’re doing all of the support.
Caregiver’s role in the fight against cancer
If any of you have ever been in the military, you’ll know that there are actual people fighting, but 90% of the forces are in a support position. Without those people, the soldier isn’t able to fight.
As the patient, Cathy’s responsibility is to get better. As the caregiver, your responsibility is to do everything else. She doesn’t have to do anything else except get better.
We’re responsible for making her feel comfortable, whether that’s rearranging her bedding, helping her with the clothes, or getting her food. Everything else is up to me, the caregiver.
What was the biggest surprise, lesson, or difficulty for you?
The hardest thing for me was to show strength. I knew I had the strength, but emotions got in the way. The emotions and the fear of losing somebody that you actually love.
I needed to be strong. I needed not to show my worry and my concerns that things might not go the way that they need to go.
I wanted to show her a positive attitude. I wanted to put on a good face for her and show her that I’m positive that things are going to get better and that eventually, we’ll get back to as near normal a life as we possibly can.
Not taking care of one’s self
I felt that I wasn’t taking care of myself. You hear this all the time. You have to take care of yourself before you can take care of somebody else and I forgot that. I was running around to the point where I was running myself ragged.
Cathy saw that and she said, “You need to stop coming in so early in the morning. Instead of coming in at 8:00 or 8:30, come in around 10:00 or 11:00, and give yourself a little bit of time.” I did and it got better.
You do have to take care of yourself. If the caregiver falls ill, then the caregiver can’t take care of the patient.
Early signs of caregiver burnout
Everybody’s different. Maybe you start to get body aches or something like that or maybe you’re not thinking straight.
For me, it was getting very irritable. I was getting tired and getting body aches.
Look out for triggers. Are there changes in their personality? Are they doing things differently? Are they forgetting things? Are they getting clumsy? Anything like that is probably a sign that you’re getting stressed out.
Differing perspectives between patient & caregiver
Cathy is a very intelligent person and she studied this quite extensively. She’s the patient. She has an idea of what she wants. Because it is her health, I usually will defer to what she has to say.
If I had a very strong opinion in the opposite way is the only time that I would speak up. But at the same time, I’d say what I had to say and then it would be her final decision.
Advantages of patient education
They say knowledge is power. But at the same time, you have to be careful when you start looking up information on the Internet. Take it maybe with a grain of salt.
If this website pops up and says you should be doing X, Y, and Z, you have to look at the website and ask yourself, “Is this a reputable website?” If you go to another website like Stanford Hospital or the Mayo Clinic, you put a little bit more weight into what they say.
I also think that once you get on these Facebook groups, they’re good and they’re bad. They’re good because they give you support. They tell you what other people have gone through.
At the same time, you have to realize that the majority of these people are on there because they have a special issue with something. When they say, “Oh my god, this is hurting me, this is doing this to me. I had this as a symptom,” maybe the majority of people don’t have those symptoms. Be aware that they can happen to you, but take it with a grain of salt.
Words of advice
Brightening up the room really helps the patient. We had these static window stickers of plants, leaves, and all these little things that would brighten up the room. When we got to the hospital room, someone had painted a little rainbow and sunshine on the windows and the stickers were still there. We just went there recently and they’re all still up there so other patients have been using them and it’s brightening up the room. It lifts your spirit more than anything else.
Bring a rolling suitcase; that’s more for the caregiver because the caregiver is going to be taking things back and forth with them all the time. They’re going to be bringing in clean clothes, taking out dirty clothes, and maybe bringing in a little bit of food or other supplies that they maybe had forgotten the first time around. It’s just a lot easier bringing in a rolling suitcase.
In a hospital, you don’t need to worry about medication. The nurses are constantly monitoring that. But when you get home, again, it’s the caregiver’s responsibility to do virtually everything, and that includes monitoring the medicine.
A patient frequently has brain fog. They don’t know what they did. They don’t know what they should be doing. It’s up to the caregiver.
Get a two-week supply of pill bottles, each marked from Sunday all the way through Saturday. Load them all up with the morning, afternoon, and evening pills. Put them all in separate containers. That way, it’s one less thing for the caregiver to worry about.
By the time you go through the first week, you still have a one-week supply and you should be refilling the empty containers. If you can’t refill the empty containers, you know immediately that you need to order medication. Ordering medication immediately rather than waiting until they run out helped us quite a bit.
Importance of diverse community support
It’s important both to Cathy and to the other patients. To Cathy, I think it’s a mental stimulation for her. Work is one thing, but work is just work.
Helping other people is something that I think she really feels gratified in doing. At the same time, with these other people, frequently, they’re at a loss. They don’t know who to turn to. A lot of these people are overseas in China and sometimes they don’t get as good information as we do over here in the United States.
