Doug shares his myelofibrosis journey after being diagnosed in 2016. He initially experienced fatigue, leading to a series of tests, which included a bone marrow biopsy that led to his diagnosis.
After following a watchful waiting approach, he started treatment with ruxolitinib. However, he continued to experience fatigue and platelet issues.
After extensive reading, he discovered a clinical trial for selinexor. Despite initial hesitation from his local doctor, he joined the trial in November 2019, experiencing positive results. Despite some side effects, like loss of appetite and weight as well as temporarily feeling off, the overall impact on his health has been significant.
Doug, now well beyond the initial life expectancy range, maintains a stable condition, visiting the Huntsman Cancer Institute every three months for follow-up. He emphasizes the importance of being proactive in exploring new treatments and encourages others to explore clinical trials for potential advancements in cancer care.
In addition to Doug’s narrative, The Patient Story offers a diverse collection of myeloproliferative neoplasm (MPN) stories. These empowering stories provide real-life experiences, valuable insights, and perspectives on symptoms, diagnosis, and treatment options for cancer.
Thank you to Karyopharm Therapeutics 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.
I was born and raised in Illinois and moved to Idaho for work in the early ‘70s. I love living in Idaho. Before I retired, I was working in Eastern Washington. My wife and I moved back to Idaho to be with family and we live outside of Boise.
I was having trouble with fatigue… When I mowed the lawn, I had to stop and rest because I was getting exhausted.
Pre-diagnosis
Initial Symptoms
I mentioned to my doctor that I was having trouble with fatigue. I noticed that when I mowed the lawn, I had to stop and rest because I was getting exhausted. At first, I didn’t notice it, but it got to a point where I was doing that every time.
I can’t remember what steps he went through with me, but after two or three different tries, he ended up referring me to a hematologist.
Diagnosis
Seeing a Hematologist
When I went to a hematologist in Washington, we went through a series of tests, including a bone marrow biopsy. That’s how I got my diagnosis in May 2016.
It was a shock. It was made doubly so because my wife was diagnosed with breast cancer a couple of weeks away from my diagnosis.
Learning About Myelofibrosis
I knew absolutely nothing. It took me a while to remember the name. They call it a rare disease. You don’t know people who have myelofibrosis. It’s not like breast cancer. Everybody knows somebody who had breast cancer so that’s familiar.
Reaction to the Diagnosis
It was a shock. It was made doubly so because my wife was diagnosed with breast cancer a couple of weeks away from my diagnosis. We were a year into my retirement and getting going with traveling when all of a sudden, both of us had cancer.
Her breast cancer was treatable. It was one of the less aggressive ones so after she had two surgeries and radiation treatment, she hasn’t had to do anything since. She’s clean every time she goes in for an examination.
Learning to live with the idea that I had cancer took a while. Through my reading and thinking about it, somehow your mind comes to terms with it. You can’t have a big open issue like that. You resolve it a little bit at a time. It comes down to it’ll be what it’ll be, but it isn’t necessarily what I would like it to be.
I was not doing that well on ruxolitinib. I had a lot of fatigue. I felt like I was going downhill.
Treatment
Watch and Wait
My disease wasn’t that far along so we decided to do what he called watchful waiting. At the time, there was only one medication, ruxolitinib, and it was not a cure. As long as I didn’t have symptoms that we were going to try to treat, we would wait.
That went on for the better part of a year. In the middle of all that, we moved back to Boise. When I found a new hematologist in town, he prescribed ruxolitinib right away.
Starting Treatment on Ruxolitinib
I was a fairly typical patient. I went through a period where I had very low platelet counts. We had to keep adjusting my dosage because at one point, I went well below 50 and I was having trouble with it. I also had anemia and it had gotten worse. I was on ruxolitinib for probably a year and a half, no more than two years.
I was not doing that well on ruxolitinib. I had a lot of fatigue. I felt like I was going downhill and my platelet counts continued to be a problem.
I wanted to find a clinical trial that I could buy into the idea of what the drug was.
Learning About a Selinexor Clinical Trial
Early on after my diagnosis, I started doing a lot of reading. I subscribed to Google Alerts where you provide keywords and it sends you links to articles with those keywords.
An article showed up from The Salt Lake Tribune and it was from the Huntsman Cancer Institute at the University of Utah. The doctor in the article had a new FDA study that he and his team were initiating. The drug was called selinexor and they saw good results in their clinical studies so they were ready to start a human trial. They described in layman’s terms how the drug worked and what it did.
It was interesting because it was unique and completely different from ruxolitinib. It had been FDA-approved and was used as a treatment for multiple myeloma. It was just a matter of trying to see if it had efficacy with myelofibrosis.
I’ve been grateful for the good fortune I had to read that article. It was a shot in the dark. Something I say to anybody is you don’t know where the answers will come from.
It always amazes me that myelofibrosis is a rare disease. Not many people have it, but it amazes me the amount of effort that the pharmaceutical community is putting into developing treatments. I don’t see how they can come out ahead financially, but I’m grateful for it. I’m all for it. If they’re willing to go for it, I’m willing.
I had gotten familiar enough with my reading. I knew there was only one approved drug that I could have prescribed for me. Now, there are four, but they’re all somewhat similar. They have different characteristics, but they’re all JAK inhibitors. If you’re going to get anything different, it’s going to have to go through a clinical trial first. I wanted to find a clinical trial that I could buy into the idea of what the drug was.
There was another drug in the trial phase with a very different mode of operation. I went to Oregon Health & Science University and interviewed with them at the same time as the selinexor clinical trial. I was considering it, but at that point, I had some issues going on with my kidneys and they wouldn’t accept me because of my kidney function.
As far as trials are concerned, if you want to get the latest and greatest technology, it’s probably the best way to do it. You have to accept that there’s a certain amount of risk. With selinexor, after you’ve been on the drug for a year, nobody knows what the effects are. That’s what they’re trying to find out.
My doctor wasn’t enthusiastic about the idea (of a clinical trial) so that put me in a quandary because I didn’t want to get in a situation where I was running contrary to my doctor’s advice.
Joining the Selinexor Clinical Trial
There was a name and a phone number so I contacted them. They invited me to Salt Lake, which was a six-hour drive. One of the problems I had when I was doing my reading was every time I came across a new drug that was in a trial, it was always in some place like Los Angeles, Houston, or New York. Travel was always a big bugaboo for me, but Salt Lake was doable. I could do a six-hour drive or a one-hour plane flight and be there.
They evaluated me and extended an offer. The doctor said that he could tell that my spleen was large. I didn’t have that much information about my spleen at that point, but his take on the whole thing was that ruxolitinib was not effective for me and the outward evidence was my enlarged spleen.
Oftentimes, we hear people say you need to be your own advocate. It’s not just up to the doctor. It’s up to you to take care of things.
I went back to my doctor and said, “There’s this drug trial that they’re starting at Huntsman and I’ve been invited. What do you think?” He wasn’t enthusiastic about the idea so that put me in a quandary because I didn’t want to get in a situation where I was running contrary to my doctor’s advice.
After a week or two, I got a call from the doctor in Salt Lake and he said, “Doug, are you going to come on the program or not?” I explained to him about my doctor being reluctant about it and he said, “Let me talk to him.” They talked on the phone and after their conversation, my doctor was enthusiastic about it so I said, “Let’s go do it.”
This was in November 2019. I had to get off of ruxolitinib for a couple of weeks before I started. That was an ordeal for me because I quit cold turkey and it was like the worst flu I ever had. I felt bad for a couple of weeks. I felt like I was sinking, but I got through that.
I was feeling the results of the drug and it was all good.
Effects of Selinexor
Within a month or two after starting selinexor, I was feeling the results of the drug and it was all good. I wasn’t keeping a journal but over time, my platelet counts started stabilizing and went up.
My hemoglobin was increasing. I was at 7.8 and my doctor told me that when a patient is 7.5 or less, they start doing transfusions. A lot of myelofibrosis patients live on transfusions. I was steadily getting closer to the territory where I would have to get transfusions.
My blood count took off from 8.7 and after a year or two, my blood count is now 12.5. It’s almost at the low end of the normal range. My platelets are in the 250 range. My hemoglobin varies somewhere between 12 and 12.5.
My white blood cell count was one of the early indicators at the very beginning. The counts were high and in the normal range, but they were at the high end of the range. The doctor noticed that they were consistently high.
White blood cell counts vary quite a bit in normal people, but mine were always at the high end of the range. I never go out of the range, but the white blood cell counts for me are high.
My anemia has been solved in the last two years that I’ve been on the drug. When I do monthly blood draws, my hemoglobin and my red blood cell counts are in the normal range, my white blood cell counts are at the high end of the normal range, and my platelet counts are in the middle of the normal range.
Before I started the selinexor clinical trial, I bought a walker because I was having so much trouble with fatigue that I wasn’t taking walks. I didn’t want to go on a walk somewhere and be exhausted. She suggested I get a walker with a seat. That way, I could park myself for a time and get my energy back.
I haven’t used that walker ever since I started the selinexor clinical trial. I’ve loaned it out to friends a couple of times. I can’t say that my energy level is the same as it was before I received my diagnosis. It’s not quite the same, but I still can go out to take a half-hour walk and it’s not a big deal for me to do that.
Because the anemia went down, my energy levels have gone up. I take selinexor once a week. We’ve adjusted the dosage. When I first was on the selinexor clinical trial, I was taking 80 mg. Now that the initial trial period is over, the doctor adjusted my dosage to 40 mg.
What’s different about being on a trial is you don’t know what to expect over time.
Side Effects of Selinexor
The problem I have gotten into with selinexor is my appetite and maintaining my weight. I’ve lost 85 or 90 lbs. It was over a year or two, but it was still a significant weight loss. It was due almost entirely to the fact that selinexor took away my appetite.
The doctor gave me different medicines to try to counteract that problem. I still take one pill daily. Food doesn’t appeal to me like it used to. When I sit down at dinner, I invariably look at my plate of food and think I don’t want to eat, but once I get started, I can finish my meal. This comes from my experience and dealing with the change.
That’s been the only hard part of being on selinexor. My doctor tried to find a dose where I would quit losing weight and maintain a stable weight. I’ve been at this dosage level for a long time. I seem to be in a place where it’s still effective but I’ve stopped losing weight and can better maintain it.
I weigh myself every day. I have heart failure and they want me to weigh myself every morning. They’re looking for weight loss as an indicator of an event, but that’s been pretty stable for a long time.
Another thing that I have to put up with is selinexor puts me in a mode where I feel off. I take the drug on a Wednesday and it’s not until Saturday or Sunday before I feel completely right again. Sometimes it’s like having the blues. Sometimes it’s not feeling quite right, but it’s never intolerable. It isn’t like I lay around and writhe. No pain goes along with it, but it’s part of what I have to put up with.
What’s different about being on a trial is not knowing what to expect over time. The doctor and I have talked a couple of times about that. I was the fourth person on the selinexor clinical trial so nobody with my disease has been on the drug for that long. The doctor said at the end of the day, maybe the main thing that comes out of this is that we’ll have a drug that will arrest the progress of the disease.
I got something that works and it doesn’t seem to be fading out on me.
Current Status
I don’t feel like I’m gaining or losing. I know that my status has improved greatly. I don’t seem to be going any further up but neither am I going down. I’m maintaining a good normal.
There’s not a lot you can do. I was first diagnosed in 2016. I’m already beyond the range of what they say the life expectancies are, which is often a mid-range of about 5 to 5 1/2 years. I’m already beyond that and I feel good.
I know that a lot of cancer treatments only last for a time. Somehow, the cancer adjusts to them and they lose their efficacy. I had a sister-in-law who had breast cancer. She came in and moved in with us in her final year. They were constantly coming up with a new treatment. But 3 or 4 months later, she’s right back where she was again until she finally got to the point where she said no more and she passed.
Cancer treatments tend to have a limited period of effectiveness. But this one, because it has such a unique method of operating, doesn’t seem to have that same life expectancy so I’m grateful for that. I got something that works and it doesn’t seem to be fading out on me.
It was my good fortune that the selinexor clinical trial worked out well for me and was doable from the standpoint of the travel.
Traveling to Clinical Trials
The biggest bugaboo in the clinical trial process is the fact that it’s such an isolated condition. There are a handful of hospitals, most of which are associated with a university. It logically makes sense that that’s where these trials would be centered, but it sure leaves a lot of people out.
I’ve talked to a number of people over time. Somebody who lives in Idaho, Montana, or somewhere similar doesn’t have any way to commit to the travel. I know people who get on a plane to go to Los Angeles because that’s where the trial is.
I get a certain amount of reimbursement for travel down to Huntsman from the University of Utah. As I recall, their accounting people figured out a rate per mile. I get a check for a little over $200. But all of that is predicated on the fact that Salt Lake is relatively close to where I live.
For me, driving down to Salt Lake was doable. One way or another, I was going to make it happen. It’s a few hundred bucks to go down there, spend the night, and come back the next day. I’ve since found that it costs me about the same to take a plane because I can go in the morning, come back in the afternoon, and I don’t have to stay overnight.
They reimburse me based on the mileage of driving back and whether I drove or not. Flying is a little more expensive. But at the end of the day, it’s a difference of a couple hundred bucks. It’s not that big of a deal. It was my good fortune that the selinexor clinical trial worked out well for me and was doable from the standpoint of the travel that was required over three months.
Follow-up Protocol
I go once every three months. I do blood tests and sampling. They take a certain amount of blood for research and a certain amount for monitoring my health. I visit with a nurse and doctor. They’ve been good people to work with.
I encourage people to be open and moderately aggressive in looking for new things that are out there.
Words of Advice
Cancer is a nasty animal. We’re learning more and more about it all the time. It’s more and more getting to be a condition that can be solved. I look at selinexor knowing that it’s not a cure, but it seems to be holding me steady enough that over time, maybe there will be a cure.
I would expect there will be one at some point in time. Somebody will figure something out. If I die two months before that gets decided, it doesn’t do me any good, but this way, at least I give myself a chance to take advantage of new developments.
I encourage people to be open and moderately aggressive in looking for new things that are out there. There are new trials that are starting all the time.
There’s a new selinexor clinical trial that’s going into phase 3, I think, which means it’s well on its way to being an approved drug. They’re doing it in combination with ruxolitinib. I’m on selinexor alone. I don’t know what ruxolitinib adds to it, but if it works, it works.
Based on my experience, there’s a lot of safety built into the process. I had the benefit of selinexor being tested for other cancers before it came to me. Some questions on safety had already been answered with other drug trials. It made it a little bit easier for me to make a decision.
Don’t think that it’s dangerous and you’re out there all by yourself. There’s a whole network of knowledgeable people who are supporting and running these programs. They don’t want to have a failure in me any more than I want one.
Special thanks again to Karyopharm Therapeutics for its support of our independent patient education content. The Patient Story retains full editorial control.
Theresa’s myeloma journey is one marked by resilience, determination, and a profound sense of hope. Her life took an unexpected turn when she began experiencing severe hip pain in 2012. Despite numerous tests and consultations, it took several months to arrive at a diagnosis of IgG kappa light chain multiple myeloma.
The initial shock of the diagnosis was met with a steely resolve to confront the disease head-on. Supported by her husband Tom and guided by her medical team, Theresa embarked on a treatment journey that included RVd chemotherapy, which initially showed promising results but eventually led to relapse. Undeterred, she enrolled in a clinical trial for CAR T-cell therapy, becoming one of the first recipients of this innovative treatment.
While the CAR T-cell therapy initially induced remission, the cancer eventually recurred, prompting Theresa to explore further treatment options. She participated in another CAR T-cell therapy trial and subsequently underwent treatment with selinexor, carfilzomib, and dexamethasone (XKd), which has been effective in managing the multiple myeloma.
Throughout her journey, Theresa has remained optimistic, actively participating in her treatment decisions, and advocating for herself. Her story is a testament to the power of resilience, hope, and the relentless pursuit of innovative treatments in the face of adversity. As she continues her journey with multiple myeloma, Theresa’s unwavering spirit serves as an inspiration to others facing similar challenges.
In addition to Theresa’s narrative, The Patient Story offers a diverse collection of multiple myeloma stories. These empowering stories provide real-life experiences, valuable insights, and perspectives on symptoms, diagnosis, and treatment options for cancer.
Thank you to Karyopharm Therapeutics 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.
It gives me hope that there are more treatment options out there. There are so many people working at different levels to help folks with myeloma be better-taken care of. They’re looking for a cure, so that’s very exciting. They’re getting closer than they have ever been.
Theresa: I was born in New York City, grew up primarily in Connecticut, and currently live in San Francisco. I went to college in Boston, moved to San Francisco a month after graduating, and I’ve been here ever since.
I had a great career in human resources. I loved that because I love helping and training people. That helped me a lot in my myeloma journey. I’ve been able to talk to other people who have myeloma, help them, and provide information. It’s always good to extend a helping hand to other people. People have done that to me as well, so I want to give back.
I have three brothers and two sisters. It was great growing up with great siblings. We all get along, which is wonderful. I love my brothers and sisters.
I used to be a lot more active. I love to swim. I love to go to the beach. I wish it was a little bit warmer, but it’s close.
I’m full of energy, loving, funny, sometimes smart, and strong, which is interesting. It’s sometimes hard to take that compliment when you go through cancer. People say, “Oh, you’re so strong. I admire you.” Meanwhile, inside, you’re freaking out.
I’ve had people say that to me a lot, so I guess it’s true. I think it comes from being from a long line of strong women in my family. I have good role models. I don’t know any other way to be.
Pre-diagnosis
Initial Symptoms
Theresa: Around February 2012, I started having bad pain in my right hip, which kept getting worse and worse.
I went to my primary care physician who took blood tests and X-rays but didn’t find anything. We kept digging further. We didn’t know what was going on. It was rough, but I kept going. I probably had 6 or 7 different kinds of blood panels to try and figure out what was going on.
For a period of about 3 to 4 months, she went from working out once a week to being unable to walk on level ground without a cane.
Tom
Scans
Theresa: She sent me to an orthopedic surgeon for a spinal X-ray. He’s the one who suggested that I get an MRI, which revealed lytic lesions. Myeloma tends to create lytic lesions. It’s a cancer of the bone marrow, so it eats away at the insides of your bones.
Between mid-February to the end of June is how long it took to get a real diagnosis. In the meantime, my pain kept getting worse and worse. I was using a cane and on pain relievers. It was frustrating to not know what was going on.
Tom: It was unpleasant and worrisome. We didn’t know what it was. For a period of about 3 to 4 months, she went from working out once a week to being unable to walk on level ground without a cane.
Diagnosis
Getting the Official Diagnosis
Theresa: I had an appointment set up at the end of June with my primary care physician. I had seen her several times since February to try to figure out what was going on.
The day before my appointment, I got an email from the doctor’s office referring me to a hematologist-oncologist. I was in denial as to what that meant. It was pretty shocking, but I wanted to wait until I saw my doctor.
They set up an appointment with the hematologist-oncologist for me to talk to. He was a lovely man and was very good. I got one of my first bone marrow biopsies. At the end of June, it was confirmed that I had multiple myeloma.
Tom: He said, “As far as survival is concerned, five years is easy.” My jaw dropped.
It was going to be a big part of her life from here on out, which meant it was also going to be a big part of my life from here on out.
Tom
Reaction to the Diagnosis
Theresa: My myeloma story started when there were a lot of emerging therapies for myeloma. I had always been pretty much healthy and didn’t have anything wrong with me specifically. I led a fairly healthy lifestyle while enjoying life, but I was shocked to get this diagnosis.
Tom: It happened pretty fast. I knew what it meant for her and it was going to be a big part of her life from here on out, which meant it was also going to be a big part of my life from here on out.
Theresa: I left his office better informed. It took me a while to absorb everything. I didn’t completely freak out. I was still in a bit of a denial.
As I talked to them, did more research, and got information about what the treatment was going to be, it slowly seeped in that I had cancer.
Theresa
Discussing the Treatment Plan
Theresa: When they discussed setting up the appointment for the first treatment, I said, “Maybe we’ll wait a few weeks.” He said, “Why are we waiting? We should do this right away.” I didn’t understand the impact of it right away.
As I talked to them, did more research, and got information about what the treatment was going to be, it slowly seeped in that I had cancer. It’s not the worst cancer, but it’s not good because it doesn’t have a cure, so that was a little shocking.
I came back the following week with Tom. The doctor very patiently and thoroughly went through what this disease was, what the treatment protocols were, and what we would do next. The good thing is they’ve developed new therapies.
RVd Chemotherapy
Theresa: The oncologist had a very specific treatment plan. He said, “The initial treatment you get is RVd (lenalidomide, bortezomib, and dexamethasone). This is the standard of care. This is the best that we can do for you.” At that time, there wasn’t a good alternative.
Tom and I talked about it. One thing that I appreciate he always says is, “It’s your body. You have to make the ultimate decision.” Over the years, we’ve talked about different treatment plans, what they’re going to involve, timing, and everything. But in the beginning, the timing was as soon as possible.
Subconsciously, I was doing things often because I couldn’t control this part of my life, so I would try to overcorrect by controlling other parts of my life.
Theresa
Side Effects of RVd Chemotherapy
Theresa: I had a fever. After my second infusion appointment, the fever got worse. They took me to the hospital, which at the time was at CPMC (California Pacific Medical Center). I stayed overnight for observation to make sure I was okay.
When you start a new therapy, your body tends to be shocked and you often have adverse reactions. Luckily, they didn’t continue.
My first reaction was itching. A couple of months later, I had a little rash, but it went away. It was nothing awful.
I had a lot of fatigue. I wasn’t sure if I was going to take time off of work. I took time off for all the appointments, but after that, I took a three-month leave of absence.
After about six months, my numbers went down. I have IgG kappa light chain myeloma. There are different kinds of myeloma. It’s so varied that it’s hard to pinpoint sometimes. I found out that what works for one person may not work for the next person.
I was on and off treatment for a while. That’s my story. It’s been a roller coaster ever since, going up and down, having longer stretches of relapse or shorter stretches of relapse depending on what’s going on.
I’ve gotten upset a lot during these 10 years, especially when I didn’t have control. That’s what affected me more than the why.
I don’t have any control over this disease. I can’t control the effects of the treatment. Even subconsciously, I was doing things often because I couldn’t control this part of my life, so I would try to overcorrect by controlling other parts of my life.
I ask questions and follow orders, so he thought I would be a very good candidate for the CAR T-cell therapy trial.
Theresa
CAR T-cell Therapy Clinical Trial
Theresa: [My disease] became refractory towards my line of treatment. It stopped working. They had a clinical trial available and he thought I was a good candidate. I asked him why he thought that and he said, “You’re in otherwise pretty good shape. You’re doing well. I know you pay attention.” I ask questions and follow orders, so he thought I would be a very good candidate for the CAR T-cell therapy trial.
I was enrolled in the bb2121 trial, which led to the very first FDA-approved CAR T-cell treatment [in myeloma]. I know my number is in there somewhere about my survival with that treatment, so that’s fun.
Clinical trials are a lot. You have to be dedicated. I remember talking to somebody who said, “Why are you doing this trial?” I said, “I want to help other people. Besides, I think it’s going to help me. It sounds really good.” You’ve got to do what you’ve got to do.
Deciding to Participate in a Clinical Trial
Theresa: I had been reading about CAR T-cell therapy and learned they had amazing results. People thought that this might be the cure for myeloma that everybody’s been frantically searching for, so it seemed like a good idea at the time.
There was a lot of paperwork to go through. There were 55 pages of study material that you had to sign your name on about 20-some-odd times, but it’s so worth it.
I trusted my doctor, Dr. Thomas Martin, who is a world-renowned myeloma specialist. I trusted his opinion and read everything.
I had some hesitation because it was still a trial, but the safety and efficacy had been already dealt with. This was a matter of figuring out the dosage, I believe. I felt it was safe and a good idea. I trusted the doctors and trusted what I read.
Within 30 days, I had a complete response. There was no myeloma detected in my system. That lasted for about 18 months.
Theresa
CAR T-cell Therapy Process
Theresa: First, they take your cells out. They had to send them to New Jersey and then back to California. Before that, there were three days of chemo. To get the CAR T cells, you have to go to the hospital. It’s like a short infusion.
I got them on a Monday and then I had what we like to call Loopy Tuesday. I did have cytokine release syndrome. I don’t remember most of that day at all. I said some strange things when they asked me questions.
After that, they hooked me up. They did so many things to make sure I was okay. I felt okay. They did tests. Doctors came every five minutes. They wouldn’t leave me alone. Everything was fine, except for that 12- to 18-hour stretch. It was otherwise being bored in the hospital.
Luckily, within 30 days, I had a complete response. There was no myeloma detected in my system. That lasted for about 18 months, which is better than the average of about a year or 13 months. I beat the odds, but it came back.
JCAR CAR T-cell Therapy Clinical Trial
Theresa: We talked about options. I didn’t go on treatment right away when I started relapsing. There was another trial that he wanted to try, which had a different target. I tried that, but only for a month. It didn’t do any good and it was hard.
Dr. Martin said, “I’ve got another CAR T trial we could try. It’s got a little bit of a different target, so maybe it’ll work.” I went on the second CAR T-cell therapy clinical trial. I did not have the bad CRS I had with the first one. I was only in remission for three months, so it wasn’t effective. That’s when we decided to go on selinexor.
Know that it could get better. If it’s your first treatment, give your body time. Talk to the doctors and the nurses. Ask them what to expect and what’s normal. Don’t be afraid to ask what’s going on. “What can I expect from this? What can I do to change this? Can I change the dosage? Can I change the timing?”
Selinexor, Carfilzomib, and Dexamethasone (XKd)
Theresa: I’m taking selinexor in combination with carfilzomib and dexamethasone (XKd). In the beginning, it was three weeks straight of carfilzomib infusions and selinexor every other week.
They said it would make me nauseous, so they gave me two anti-nausea drugs while I was getting the carfilzomib. I had two kinds of pills to take at home: one at night for three days and then another to take any other day that I felt nauseated.
It did usually present with some nausea for about three days. I experienced extreme fatigue, although we found out that it was due to the anti-nausea medicine that I was taking at night, so we changed it.
I take three pills in the morning before I get my infusion and on selinexor days. Five or six hours after I get my infusion, I take dexamethasone.
I’m very lucky to have responded to a lot of different treatments. Most of my treatments have been pretty good.
Theresa
Adjusting to New Treatments
Theresa: Know that it could get better. If it’s your first treatment, give your body time. Talk to the doctors and the nurses. Ask them what to expect and what’s normal. Don’t be afraid to ask what’s going on. “What can I expect from this? What can I do to change this? Can I change the dosage? Can I change the timing?”
With dexamethasone, sometimes, it depends on the dosing schedule because it can keep you awake. Work with your body to know the best time to take it and if you can make adjustments. Ask the doctor, “What else can I do?”
This is one mistake that I made in the beginning. I thought if I said something to my doctor, they would address it, but they don’t always do that. If you say something, they’ll listen and write it down, so you have to specifically ask them.
I’ve been on this regimen since September 2021. Again, beating those odds.
One thing I know is that I’m very lucky to have responded to a lot of different treatments. Most of my treatments have been pretty good. Maybe a quarter to a third of them didn’t work, but others have, so I’ve been very lucky to have that percentage work for me.
Future Treatments
Theresa: I don’t think about them specifically. I’ve already discussed what my next treatments would probably be. I have a choice between a bispecific antibody trial or another kind of CAR T-cell therapy clinical trial on a completely different target.
It’s likely that within some amount of time, maybe 3 to 6 months even, I’ll have to go on another treatment. Selinexor has worked for way longer than expected and it’s been well-tolerated.
I have hope. I’ll still be around. I still have stuff to do. I’m not ready to go yet.
Theresa
Words of Advice
Tom: When we got the diagnosis, I said, “Okay, we’re on our way. We got a name. We can pin this sucker down.” We’re getting closer to 10. Median survival rate was 7 ½ years and she’s beaten the hell out of that.
Theresa: I have hope. I’ll still be around. I still have stuff to do. I’m not ready to go yet. It gives me hope that there are more treatment options out there. There are so many people working at different levels to help folks with myeloma be better-taken care of. They’re looking for a cure, so that’s very exciting. They’re getting closer than they have ever been.
It’s about survival, doing the right things, getting support, and being tough.
Special thanks again to Karyopharm Therapeutics for its support of our independent patient education content. The Patient Story retains full editorial control.
Relapsed/refractory Hodgkin’s thriver Sam Siegel and Dr. Andy Evens from Rutgers Cancer Institute discuss the latest in Hodgkin’s lymphoma treatments and how to reduce the toxicity of treatments so patients can live their best lives after cancer.
Get updates on recent and upcoming clinical trials, how to manage treatment side effects, and new approaches to mitigate chemo toxicity.
Know more about the role of stem cell transplant and radiation in the treatment of Hodgkin lymphoma, and how to create personalized Hodgkin treatment plans.
Learn what questions to discuss with your care team, lifestyle changes to improve quality of life, and how to have a holistic approach to your care.
Special thanks again to Pfizer for its support of our independent patient education content. The Patient Story retains full editorial control.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Dr. Sam Siegel: I’m a relapsed/refractory Hodgkin’s thriver, mom of three, loving wife, primary care provider, and survivorship medicine practitioner. I’m here to talk about Hodgkin’s lymphoma, the latest treatments focusing on reduced side effects, and a holistic approach to care.
I want to give special thanks to Seagen for supporting our educational program. Their support helps programs like this become more available and free for our audience. We want to note that The Patient Story retains full editorial control of this entire program and that this is not meant to be a substitute for medical advice.
I’m excited for this conversation with Dr. Andrew Evens from Rutgers Cancer Institute to talk about the latest trials in Hodgkin’s lymphoma and how to reduce the toxicity of treatments so that we can live our best lives after surviving cancer.
Andrew Evens, DO, MBA, MSc
Sam: I have the privilege of being with Dr. Andrew Evens, a specialist in Hodgkin’s lymphoma at Rutgers, leading clinical trials for more than 20 years, and also the medical director of RWJBarnabas Health.
Dr. Evens, can you tell us more about your path into Hodgkin’s lymphoma treatments and all of the amazing things that you do for the lymphoma community?
Dr. Leo Gordon, who was and is still the director of the lymphoma program, Dr. Jane Winter, one of our recent American Society of Hematology (ASH) presidents, Dr. Martin Tallman, and Dr. Steve Rosen—stalwarts in the field of hematologic malignancies.
I had an early interest. This was over 20 years ago and at the time, we knew that Hodgkin lymphoma was pretty curable. We’ve known that since the 1980s, but nothing’s 100%.
Sometimes, it doesn’t always work or there are side effects. Even though we have known for a few decades that it’s very treatable and curable, we’re always trying to do better and do so with more tolerable targeted treatments. It’s an active area of study.
I was finishing my training with a global network of Hodgkin lymphoma experts. There are many different meetings and conferences we all go to. There’s one in particular in Cologne, Germany, that they’ve had for over 20 years. They’ve been amongst the world’s leaders in Hodgkin lymphoma research, clinical research, and basic science research.
At the time, Hodgkin lymphoma experts across the world met there every three years. Now, it’s every two years. When I say all of the experts, it’s not just clinicians. It’s soup to nuts Hodgkin lymphoma. It’s epidemiology. What causes it? It’s etiology. What’s in the microbiology and genomics? It’s diagnosis, treatment, and, importantly, post-treatment survivorship. It’s an incredible meeting.
When I went to that first meeting as a young whippersnapper hematology-oncology fellow, I knew that was for me. Something called to me about it. Knowing that so many different aspects related to Hodgkin lymphoma, I’ve been fortunate to be involved in the field for over 20 years now.
Sam: I did a lot of hematology-oncology in my internal medicine residency. I started as a hospitalist where I did a lot of hematology-oncology and had that lens with end-stage pathology where people come into the hospital very sick and then to outpatient medicine, seeing people sooner and trying to get them diagnosed sooner. Then I got cancer.
Sam’s Hodgkin Lymphoma Story
Sam: My story began in 2021 when I began feeling super exhausted. I thought I was just tired like every other doctor-parent was during the pandemic. A lot of people I knew were tired. I had a lot of justifications for why I was feeling that way.
I started coughing, but there were some wildfires in California so I thought maybe that was it. Maybe I was getting asthma.
When I developed a rapidly growing, rock-solid, painless lump above my collarbone, I thought, Oh, gosh. I have cancer. Once that showed up, I was no longer in denial and got a whole series of tests that ultimately led to a diagnosis of stage 2AE Hodgkin’s.
In the beginning, there was some controversy about my staging. I had some lung involvement and my understanding at the time was if there’s lung involvement but it’s connected to the major tumors that are there, it’s still stage 2 with extranodal (outside of the lymph nodes) manifestations versus stage 4. That was the first decision-making point. What’s my stage and how would that impact my treatment?
It was a complete shock. I was a marathon-running doctor mom, minding my own business, doing life, and then boom—Hodgkin’s diagnosis. I believed myself to be healthy, even though I was feeling symptomatic.
I started what was considered back then the standard upfront treatment called ABVD chemotherapy. My cough went away with my initial chemotherapy and after about two months, the cough came back.
Around that time, I had a scan that showed that my disease was responding well so we decided to drop the bleomycin. We thought I was developing a bleomycin-related cough after the initial cough had gone away.
I continued the next four months with AVD. I got a scan at the end of six months and had no evidence of disease. That was very exciting but also troubling because I felt bad and I wasn’t sure why. Do I feel bad because this is how a body feels after having a multiple-drug regimen for six months or is there something else going on?
I had another PET scan after developing symptoms of relapse and that showed that I had most likely developed a relapse. I had to undergo various procedures to get a tissue sample to confirm. Within a month, I was diagnosed.
What started as a seemingly “simple cancer” or “winning the cancer lottery” as some people are told, I realized very quickly that the treatments are hard, especially some of the older treatments before you get to the immunotherapy and the newer discoveries. Even if you get cured or have no evidence of disease, it can come at a great cost.
Cancer Survivorship
Sam: I found my way to the field of cancer survivorship and I’m super pumped about that and to talk to you about holistic health and your role at RWJBarnabas Health. Because I’m also doing an integrative medicine fellowship, I realized how incomplete our medicine is.
Allopathic Western medicine saved my life, but it also decimated my health at various points so I realized we need other tools. We need to embrace this other field of medicine to complement that, to help people withstand the toxicity of treatment, and to recover and rehabilitate from it when they’re done. I’d love to hear your thoughts.
Dr. Evens: There are so many good clinical trials happening across the world. Every clinical trial asks a slightly different question. At the end of the day, however good clinical that trial is, how is that applied at the bedside?
Sometimes, for better or for worse, treatment ideations and recommendations end up becoming one size fits all and we know every patient is different. I always say that there are a lot of commonalities between Hodgkin lymphoma and non-Hodgkin lymphoma, but each patient is unique and different.
How do we take large amounts of data, amalgamate it, and apply it to the patient? It’s difficult because we have lots of data and there are recommendations and certain guidelines.
But what about you, Dr. Sam? For an individual patient with your stage, your albumin, and your lymphocyte count, there might not be one best therapy. There might be treatment options A, B, or C. But are there data or algorithms that I can put my characteristics, desires, hopes, and patient preferences to say if I go with A, B, or C, here’s what I would expect in acute within 1 or 2 years, and here’s what I would expect moreover 30 years down the road?
Sam: My mindset shifted. In the beginning, I was so afraid. I’m a young mom with my whole life ahead of me. I was so afraid of dying so I thought, Let’s hit it hard. Let’s do everything. Let’s get the strongest therapy.
As I began to move through treatment and experience, there were some pretty devastating adverse effects that I wasn’t sure how long they would last. As a doctor, I was primarily concerned with the cognitive impairment. I experienced severe chemo-related cognitive impairment, which is the worst form of chemo brain.
I gained 40 lbs from steroids and became severely metabolically ill. I got the rash that people get when they are going to develop diabetes called acanthosis nigricans. My glucose was high and my cravings changed. I wasn’t sure that life as I knew it would ever return.
When I developed symptoms of a relapse, my mindset was different, even just one month later. Let’s not give it everything we’ve got. Let’s make some decisions about how I can take the least amount of therapy to get me into remission and then to transplant.
New Targeted Therapies
Sam: Right around that time, science had shown that people were doing single-agent brentuximab as a bridge to transplant. If that didn’t work, then you could get ICE or some of the other stronger therapies. But there was science to support that single-agent brentuximab was a reasonable thing to do and had lesser toxicity than some of the old bridge therapies.
I was so grateful because I could not psychologically, mentally, and physically handle the more traditional, cytotoxic chemotherapies that I had upfront and that were previously used as part of salvage regimens.
I took brentuximab, initially at the exact dosing used in the trials. Then I developed a strange, rheumatoid arthritis-type illness—bad morning stiffness, joint swelling, pains, and these crazy rashes. Those got better with dose reduction.
Individualizing Hodgkin’s Lymphoma Treatments for Patients
Sam: We’re starting to talk about individualizing therapy for the person, for their circumstances, for their medical comorbid conditions, and to make decisions that way.
Dr. Evens: It sounds like you had a tough time and that’s where everyone is so different. Some patients do relatively well with chemotherapy. Then there are weird side effects that pop up. You went through that roller coaster and were able to course-correct where needed with the dosing.
There have been two big therapeutic breakthroughs in the last 10 years for Hodgkin lymphoma in particular.
We figured out over 20 years ago that one of the antigens that sticks out of a Hodgkin lymphoma cell is called CD30. Brentuximab vedotin, which was first approved in 2018, is an antibody-drug conjugate that attaches to the Hodgkin lymphoma cell, has a little bit of chemotherapy attached to it, and then gets inside the Hodgkin lymphoma cell.
Immunotherapy
Dr. Evens: After that came checkpoint inhibitors or immunotherapy that aren’t just approved for Hodgkin lymphoma, but also for more than 12 different cancers, like melanoma, lung cancer, and renal cancer.
It’s a fascinating science and, in a way, it’s the antithesis to chemotherapy. How does chemotherapy work? It kills cells that grow fast. Not very specific in the body. You hope it knocks out lymphoma cells, but the side effect is it affects anything that grows fast. What are some of our fastest-growing cells? The hair and the immune system. Though chemotherapy is not so targeted, we still use it.
Current and future medicine is more about targeted therapy. How do checkpoint inhibitors work? It reinvigorates the patient’s immune system, the T cells in particular. Simplistically, there are some cancers like Hodgkin lymphoma that have receptors that don’t allow the patient’s immune system to engage with the Hodgkin lymphoma cell. It’s almost like creating a force field.
What these inhibitors do is take down the force field and let the patient’s immune system go after and take down the lymphoma. We’ve learned how to use these medications when the disease relapses, but also for newly diagnosed patients as well through clinical trials.
Sam: I’m so excited because within the last 5 to 10 years, things have changed so much. If I was diagnosed with the same clinical situation as I was back in 2021, my treatment now might be different. That’s pretty crazy to think about because, for so many decades, it was the same: ABVD and possibly radiation.
Decreasing the Toxicity of Therapy
Role of Radiation in Hodgkin’s Lymphoma Treatments
Sam: Where does radiation fit in all this? I haven’t even heard much about radiation lately.
Dr. Evens: It still fits for early-stage or limited-stage disease. Yours was a tricky one. We still have to figure out the stage Es. If it’s disseminated extranodal involvement, it’s stage 4. If it’s a lymph node extending towards the lung, that’s more extranodal, but there can be some grey zones. It can be tricky.
Radiation still has a role in limited-stage disease, especially stage 1. For stage 2, the question there is: do I give less chemotherapy and low-dose radiation or more chemotherapy? There’s absolutely no right answer. There’s more disease control. It’s more effective to receive radiation. We always debate the trade-off. What about some of those late consequences? Can radiation contribute to that?
Late-Term Side Effects of Treatment
Sam: Can you mention some of those?
Dr. Evens: It partly depends on the treatment, whether chemotherapy or radiation.
One is arterial disease. Now it depends on location. Radiation techniques have gotten much better over the years. If there’s any scatter of radiation, there could be some carotid involvement or if there’s radiation in the chest area, there’s cardiac involvement. It’s not like there’s an incredible risk. The risk of arterial disease is a little bit increased.
That’s not to say there aren’t risks from chemotherapy, by the way. When we look at chemotherapy alone, there is an increased risk of myocardial infarction later in life because adriamycin can irritate the heart not just acutely but later in life. It rarely happens but it still does.
Another secondary or late consequence we think about, unfortunately, can be second cancers. It’s hard enough to have one, but sometimes, 10, 20, or 30 years later, there can be secondary breast or thyroid cancer. Those are more serious late effects.
Other still serious but maybe not life-threatening late side effects could be hypothyroidism, fatigue, or neuropathy.
At the end of the day, clinical trials are important as they’ve been able to show how to get these novel agents approved and how to bring them to the front line, but we also need to study those late consequences.
Clinical Trials in Hodgkin Lymphoma
Targeted Therapy
Sam: Can you mention clinical trials concerning targeted therapy and immunotherapy?
Dr. Evens: Many of the ones that garnered its approval for relapse don’t have an acronym or a name because they’re often phase 2 trials. We think treatments need phase 3 studies to garner approval. But in uncommon diseases like Hodgkin’s, which affects about 8,000 patients a year in the United States versus 90,000 with non-Hodgkin’s, it’s hard to have randomized data. With a rigorous, large phase 2 study, it can garner approval.
Thankfully, there have been a couple of phase 3 studies. One of them that garnered the approval of brentuximab vedotin in the maintenance after a transplant was called AETHERA. It was a phase 3 blinded randomized study.
The standard of care for relapsed Hodgkin’s is usually some form of therapy, whether chemotherapy or brentuximab, then a transplant. AETHERA added one time a month for a year of maintenance therapy and showed a pretty significant benefit that garnered that approval. But why do we have to wait for a relapse? What if we do it in the beginning?
An important global study called ECHELON-1 was published and has been republished a couple of times in the New England Journal of Medicine. It showed replacing bleomycin with brentuximab vedotin (BV-AVD) compared to ABVD.
The real landmark breakthrough in that study was not just showing progression-free survival, but an overall survival benefit, which we had never seen in the field. You want an overall survival benefit and some of the updated analyses of ECHELON-1 showed that, so that’s great but we’re not done yet.
BV-AVD might be the new king of the hill. How can we knock you off? The most recent phase 3 randomized trial was conducted in the US by our cooperative groups. It was called SWOG S1826. All the groups, including the pediatric oncology group, participated in this study. That’s another important point. We’re working with our pediatric colleagues to go after Hodgkin lymphoma.
That study compared nivolumab, one of the checkpoint inhibitors, and AVD (N-AVD) to brentuximab vedotin and AVD (BV-AVD). It hasn’t been published yet. It’s been presented a couple of times. Long story short, at least at one year, checkpoint chemotherapy looked to have a higher progression-free survival than BV-AVD.
As we go through these studies, we’re trying to not only get better but also get better and have fewer side effects.
Progression-Free Survival vs. Overall Survival
Sam: Could you explain the difference between progression-free survival and overall survival and why that’s exciting?
Dr. Evens: Progression-free survival means the length of life might not be different, but I’m progression-free or in remission longer.
When we first looked at ECHELON-1, we saw that progression-free survival was improved by about 10%. Another way to say that is, for example, for patients treated with BV-AVD, at three years, around 80% of patients were still in remission versus 70%, or maybe it was 85 and 75. That’s good. I’d rather be in remission longer, but I’d also like to live longer. That’s overall survival.
Before ECHELON-1, there had never been a study showing better, longer overall survival compared with classic ABVD. Part of the reason is that if you have a good second therapy, even though there can be side effects, it’s easier to modulate overall survival.
What they showed when they looked at six years for BV-AVD was overall survival improvements. That’s a game-changer in the field. It was already FDA-approved based on progression-free survival, but I think it became more common in use after the overall survival data.
Sam: These are exciting times. I hope to never need the services of a hematologist ever again, but I do have hope that should I experience another relapse, heaven forbid, there are good treatments out there to provide remission and quality of life.
Pembrolizumab
Sam: Tell us about pembrolizumab.
Dr. Evens: Pembrolizumab is another checkpoint inhibitor. Nivolumab and pembrolizumab are much more similar than different. A lot of their studies are keynote studies from that company and it has a number. In particular, Hodgkin’s was KEYNOTE-087. They keep adding numbers throughout all the different cancers. That was initially approved as nivolumab for relapsed Hodgkin lymphoma. That garnered that approval, one of the keynote studies, like nivolumab.
SWOG S1826 was for advanced-stage disease, so stages 3 and 4. When something gets approved for a certain situation, a certain stage, and for certain ages, what about for limited stage or early stage?
For many patients, a common treatment modality for early stage is six months of chemotherapy. Others might receive four cycles of chemotherapy and radiation. We were planning this study for the United States through the US cooperative groups. This study involves the pediatric oncology and adult groups. The Children’s Oncology Group is leading it, but we’re all working together.
There is a new national, high-priority study called AHOD2131. It’s comparing the standard of care that we talked about for early-stage disease versus everybody on the new arms of two cycles of chemo and the rest, targeted therapy: a combination of brentuximab vedotin and a checkpoint inhibitor.
The hypothesis is it’ll be more effective and likely better tolerated. That’s an ongoing study. It opened in the summer of 2023 and is planning to enroll over the next couple of years.
What’s great about that study is not that it incorporates novel therapeutic agents in place of cytotoxic chemotherapy, but over 10 to 12 years, it’s going to study some of the late-term effects and that’s sometimes a gap with clinical trials.
They’re great in the first couple of years then they fall off and don’t have the resources or funding to study late-term effects. In great collaboration with the National Cancer Institute and CTEP (Cancer Therapy Evaluation Program), they are providing resources not just to study the initial 3, 4, or 5 years, but extend beyond 10 years, which is fantastic.
Understanding Clinical Trials
Sam: You brought up some great points and I want to highlight this for patients because I don’t even think I felt empowered to think these things or ask some of these questions with the initial shock of the diagnosis.
Clinical trials are not just for people who have failed multiple lines of therapy. Clinical trials could be for multiple situations. How do we de-intensify therapy? How do we make different therapeutic decisions? How do we start using therapies that were used in a very specific situation, like only for relapsed/refractory, and use them for early-stage patients upfront? That’s what some of these trials are showing.
What advice could you give to patients?
Dr. Evens: Be an advocate for yourself or your family member because this is your life. Not to minimize it, but there should be no intimidation or concern of talking to the oncologist.
99.9% of oncologists want the best for their patients. Sometimes, the provider might not always bring up a clinical trial because they might not have access. But I would encourage you to ask if a clinical trial is right for you.
I wish we had a clinical trial for every condition. There’s always a semi-standard of care. We’re always trying to do better or if not do better, do the same with fewer side effects. The only way you can do that is ultimately in a clinical trial.
These are very sophisticated studies where we’re hopeful. Of course, we have to prove it in that clinical trial. The vast majority of clinical trials are with targeted agents or immunotherapy agents. I would implore the patients and patient family members to, if not self-advocate, reach out to other foundations.
Sam: On that note, if you have any questions regarding how to look up and navigate through clinical trials, The Leukemia & Lymphoma Society has a clinical trial support center with free access to experts who can guide you through that process.
Dr. Evens: The best outcomes are usually with the most informed patients who know the different options. In Hodgkin lymphoma, very, very often, there’s not one right way to treat it. There are different options. There shouldn’t be anything scary or wrong with getting second opinions. We’re often happy to help.
Sometimes we won’t have anything different to offer or it might not even be a clinical trial, but a little nuance on dosing or something based on patient characteristics or comorbidity. We might want to make a certain adjustment a priori to a treatment. When that’s all you do for 20 years, you’ve seen it all and every condition, and we’re happy to lend any advice we can.
Role of Stem Cell Transplant in the Treatment of Hodgkin Lymphoma
Sam: Where does transplant fit in all of this? I had an autologous stem cell transplant. I’m so grateful for it, but it was tough. I had beam therapy as a conditioning regimen because I had hemorrhagic cystitis from cyclophosphamide when I was mobilizing my stem cells.
Dr. Evens: You had almost every side effect.
Sam: I did and then I had pneumonitis from carmustine. I believe that I had this cancer at this time in my life and had such a tough course so that I could learn about these things, be an advocate, and go into longitudinal survivorship.
I know now some of the questions to ask, some of the things that can happen, and how hard it can be, even when it’s the “good cancer.” I did just like AETHERA—I had one year of post-transplant brentuximab.
Dr. Evens: Did you do okay with it?
Sam: I did. I ended up getting a dose reduction because we learned before I had a transplant that I needed the dose-reduced brentuximab as well. I had some neuropathy, which wasn’t just pain. It was falls, clumsiness, and dropping things.
Dr. Evens: It was affecting your function.
Sam: It was. I do a lot of procedures so for people like me who work with their hands or do a lot of things with their hands or feet, it could be important. The neuropathy is still there, but it’s recovering.
Autologous vs. Allogeneic
Dr. Evens: For over 30 years, transplant has been the standard for Hodgkin lymphoma in younger patients. When we say younger, we mean less than age 70. The patient receives some new treatment, gets back in remission, and then a one-time transplant.
When we say transplant, it’s an autologous transplant, which uses your own cells so it’s not a transplant. It’s one cycle of high-dose chemotherapy followed by a rescue using your own stem cells so you bounce back after the chemotherapy. We do an immune system transplant or allogeneic transplant, but we rarely have to do this for Hodgkin’s.
As much of a standard of care as it’s been, we’re revisiting everything and asking: does everybody need a transplant? Now that we have brentuximab vedotin and checkpoint inhibitors, can we lean on these targeted therapies for certain patients?
Studies take months and sometimes a couple of years to plan because you want to get it right and have the latest treatment and data. We’ve been talking about it and planning it to ultimately prove it because it can’t just be an idea. We have to prove it. It would have to be a clinical trial where there’s some randomization to the standard transplant or no transplant.
It’s not done yet, but I’m hopeful that is something we can explore and that we can cure relapsed Hodgkin lymphoma without a transplant. But right now, that’s not the standard of care. It would still be a transplant.
Continued Monitoring
Sam: How are we monitoring patients with Hodgkin’s lymphoma?
Dr. Evens: There are different practice styles and part of the reason is it also comes back to data. We don’t want to do a scan just to do a scan. Is it helpful? Does it tell us information?
What had been standard for a while, whether for initially diagnosed or for relapsed, is when there’s a transplant, the vast majority of the time, we count two years from diagnosis.
During that two-year time mark counting from the initial diagnosis or the initial relapse, some of us will usually see patients in the office every three months for a physical exam, history physical, maybe some blood tests, and sometimes a CT scan every six months.
Not everyone does scans. They think there’s lead time bias and it only maybe helps you pick it up a little bit earlier but doesn’t improve survival. But if someone does scans, they should not do it past the two-year mark.
There’s radiation with CT scans. We don’t think of it, but for many types of CT scans, that’s equal in radiation to 500 chest X-rays. Imagine getting 500 chest X-rays. It’s something we want to use if it’s helpful, but not too much.
But what about after two years? What about after five years? Ten years? That’s where I think we need a greater focus and an opportunity on bonafide survivorship clinics.
There are some good algorithms. I know our pediatric oncology group at the Rutgers Cancer Institute has a computer program where they can put in the patient’s age, treatment, and whether they’ve undergone radiation, then based on the best available data, it will generate your primary care follow-up.
None of the recommendations are likely, but they’re usually evidence-based to show that there’s some impact on that. I would say individualized, but it’s something that we need to make sure, as a community, our patients know that the survivorship aspects are still very important.
It’s not just about breast cancer screening, heart screening, etc. What about chronic fatigue? What about anxiety and other emotional disturbances that can happen? In a survivorship clinic, like what we have at the Rutgers Cancer Institute, you have experts like physicians, nurses, and social workers surrounding the patient throughout the life-long care continuum.
Sam: I love that and I love that you made the distinction between surveillance and survivorship because I think surveillance is a big part of survivorship, but it’s not all of survivorship.
My understanding in speaking with people from the NCI Office of Cancer Survivorship is that a hot topic within the survivorship research community right now is what is a mutually agreed upon definition. It includes surveillance. But it’s also cancer-surviving mindsets and how we plan for life after a cancer diagnosis, including oncofertility, social-emotional well-being, family planning, and reintegration in work life, society, or family. How do you live your life after you’ve had a cancer diagnosis, regardless of your remission status or where you’re at and all that, including making sure that you get your scans and your bloodwork and all that?
I think a lot of people in the community are starting to realize that it’s so much more. I’m hoping that, ultimately, it’ll be a board-certified fellowship in the next five years or so with core competencies like this is what a survivorship clinician should know and be able to talk to patients about.
Dr. Evens: Absolutely. We talked a little bit about the HoLISTIC Consortium and that’s one of our goals. Despite the commonality in terms of the number of diagnoses, it’s remarkable that we’ve come together under this consortium and have done so in the last few years and that’s to gather the world’s data of clinical trials.
In many of those clinical trials we talked about, this is individual patient-level data. It’s de-identified, careful individual patient data put into a huge master database with a common data model and data dictionary so they all come in a readable and harmonized fashion.
We’ve also knitted together and synthesized large amounts of clinical trial data. There are survivorship clinics and survivorship cohorts out there across the world collecting data over decades at Princess Margaret in Toronto, BC Cancer Vancouver, Stanford in California, Australia, the Netherlands, and Denmark.
Over the last few years, we have put together 20,000 cases of patients in clinical trials and survivorship registry cohorts to give objective information. If you did A, B, or C, here are your expected efficacy and side effects based on your individual characteristics.
But also to simulate, as best as we can tell, based on this treatment and at this point in your cancer journey, what we estimate to be your 10-, 20-, and 30-year late consequences to make a more personalized survivorship plan and not just an initial treatment plan. The way we’re going to do that is through large amounts of big data and data analytics with some machine learning mixed in.
Sam: That’s exciting because one of my big aha moments with starting to participate in the survivorship community is that survivorship is defined as anybody living after a cancer diagnosis, but it doesn’t seem to be routinely delivered that way. It seems that it’s piecemeal and it’s focused on a couple of cancers.
I believe that longitudinal survivorship is the way. We should deliver survivorship from the time of diagnosis, in parallel with oncology care that’s delivered by the oncologist. If we know we’re going to give a person cardiotoxic chemotherapy, let’s not wait until they develop heart disease 20 years down the road to start paying attention to heart disease risk. We could put people through intensive lifestyle medicine therapies where we talk about diet and exercise, check their A1C and cholesterol levels, monitor their blood pressure, and talk about heart health in the beginning.
Dr. Evens: We have some patient advocates and we’d love for you to become involved to some degree as a patient advocate and a physician expert as part of HoLISTIC. We’re still gathering and building data, but we’re looking forward to starting how we best apply this to patients and the medical community.
Final Takeaways
Sam: This has been just such an exciting conversation. What are some final takeaway messages that you have for patients, providers, and advocates?
Dr. Evens: It starts with an informed provider and informed patients. Is Hodgkin lymphoma treatable and curable? Yes, whether it’s newly diagnosed or stage 4, even if it comes back once or twice, but there are different treatment options.
When it comes to treatment options, how effective are they? How will the patient tolerate it in the moment and later in life? The number one goal is to cure but do so with minimal side effects. It comes back to personalized cancer care.
There has been great progress over the last few decades. We still have room to have treatments that are better tolerated. We’re thankful to have well-informed patients, patient advocates, scientists, clinicians, epidemiologists, and survivorship experts. Everyone is coming together, laser-focused on Hodgkin lymphoma to continue to advance the field.
Sam: I agree. I think that there’s a palpable shift in cancer culture. We need to do more than just focus on not dying. Let’s focus on the living part. How do we help people fully live after facing a cancer diagnosis? This is a really exciting time. I’m grateful to have had this conversation with you and can’t thank you enough for your time.
Special thanks again to Pfizer for its support of our independent patient education content. The Patient Story retains full editorial control.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Initially misdiagnosed due to overlapping symptoms with his existing condition, Matthew experienced concerning symptoms such as dark urine, pale stool, and intense itching. Eventually diagnosed with metastatic pancreatic cancer, Matthew underwent different combination chemotherapy treatments, including FOLFIRINOX (leucovorin calcium or folinic acid, fluorouracil, irinotecan hydrochloride, and oxaliplatin) and GAP (gemcitabine, nab-paclitaxel, and cisplatin).
Despite setbacks and the grim prognosis associated with pancreatic cancer, Matthew’s tumor responded positively to the new chemotherapy regimen, leading to tumor shrinkage and the disappearance of metastases in the liver. Following a successful Whipple procedure, Matthew emphasizes the importance of not being defined by statistics and advises others facing similar challenges to live life to the fullest while also taking their health seriously.
His story highlights the unpredictable nature of cancer treatment, the importance of advocating for oneself in medical settings, and the significance of cherishing each moment, even in the face of adversity.
In addition to Matthew’s narrative, The Patient Story offers a diverse collection of cancer stories. These empowering stories provide real-life experiences, valuable insights, and perspectives on symptoms, diagnosis, and treatment options for cancer.
I live in Hazel Park, Michigan, with my girlfriend Natalie and our pug Monique. Because of the nature of my illness, I haven’t had a job in three years, but in my former life, I was finishing a PhD. I was going to be an academic.
Pre-diagnosis
Initial Symptoms
The most popular narrative surrounding pancreatic cancer is that not only is it very lethal but also very difficult to diagnose. The pancreas is deep in the body. The earlier symptoms are very nuanced, can go unnoticed, and can also be misdiagnosed as a multitude of other things. By the time you’re experiencing symptoms, the cancer has spread outside of the pancreas. I don’t want to say it’s too late, but that’s what conventional wisdom is.
I was diagnosed with Crohn’s disease when I was 25. Gastrointestinal distress, which is one of the more perceptible symptoms of pancreatic cancer, was par for the course for me. I probably wouldn’t have noticed even if I didn’t have Crohn’s. I lost some weight over the months, but it wasn’t until late January 2021 that I started to experience starkly distinct symptoms.
It was the COVID pandemic. I lost my job and moved to a different city to help my friend with his business. His business closed and he moved away, so I was alone when all this started.
I had dark urine and bone-white stool. I didn’t even notice the stool color for a while. At first, I thought I was hungover. I had a few beers the night before so I drank some Gatorade and lay in bed, but the urine did not get lighter.
My skin started to itch. The bathroom symptoms were pretty jarring, seeing urine that dark and poop that pale, but the itching was probably the worst. The palms of my hands and the bottoms of my feet itch. It was worse at night. I never felt anything like it before and those are hard places to scratch.
After a whole night of itching, I put my hands and feet in the tub under hot water to numb the sensation. In retrospect, it’s jarring to think about burning my hands and feet to alleviate the pain, but the itching was that significant.
Not everyone gets the itchiness. There seems to be some controversy because not every pancreatic cancer awareness campaign includes itchiness. I experienced it and it was horrible.
When something started to happen, I sat on it for 48 hours before I finally told someone. It wasn’t the most responsible, but in retrospect, not that bad. I was in a long-distance relationship with a woman I knew from graduate school. I told her and she said, “You should go to the doctor.”
I have a lot of medical anxiety. I have never been a good patient. For someone with such anxiety about doctors and hospitals, I needed someone to tell me.
Going to Urgent Care
I had recently moved to Durham and didn’t even have health insurance, but I went to an urgent care center. My blood test results showed that my bilirubin was high. We get some more tests back. The nurse said, “You don’t have a doctor here yet and these test results are troubling. You should go to the ER.”
Going to the Emergency Room
I went home to sleep because I hadn’t slept in three nights. I was so tired that despite the itching, I passed out. Early the next morning, I went to the ER and that was the beginning of my journey.
They admitted me to the hospital and ran some more blood tests to see what was going on with my liver enzymes. They did an ultrasound and an endoscopic ultrasound.
Bile Duct Stricture
They found that there was a stricture in my bile duct. Your liver produces bile, a digestive enzyme stored in your gallbladder and then released into your small intestine to digest fats and other foods. The tube that brings the bile down goes through the head of your pancreas. That tube had a stricture, so it was closed off. When bile can’t be distributed normally, you end up depositing it in your blood and your flesh, and that causes jaundice and elevated liver enzymes.
With the endoscopic ultrasound, they were able to place a stent in my bile duct in the hope that it would stretch it out. They told me to come back in a few weeks to have another endoscopy and remove the stent.
There was no sense of urgency. I was an otherwise healthy person with a history of colitis. They didn’t think that this was anything scary.
After they removed the stent, the symptoms came back, so they decided that it was my gallbladder causing the symptoms. With pancreatic cancer, it’s very common for people to assume that it’s a gallbladder issue. They decided to take my gallbladder out. After the surgery, the symptoms return.
It was late April. I went to my gastroenterologist’s office, who was the one who did the endoscopy. She said, “I don’t know what’s happening, but you for sure don’t have cancer. We have done so many brushings and you definitely don’t have cancer. If you have cancer, I will roll over in my grave.” I left her office feeling pretty confident.
Diagnosis
Getting the Official Diagnosis
Three hours later, I got an automatic notification on my phone from MyChart. One of my cytology reports came back. It said adenocarcinoma. I didn’t know what that meant, but I knew it wasn’t good.
I sat with that for about two hours. Then the surgical oncologist who did my gallbladder surgery called me. My case got automatically referred back to him. He was out of town and called me using his personal cell phone.
I told him, “This lady told me I definitely did not have cancer and now I do so I’m freaked out,” and he apologized. My surgeon is the salt of the earth. He calmed me down. I don’t know if he remembers it this way, but I’ll never forget this conversation. He said, “If this is cancer, the tumor’s very small and I should be able to get this. I’m confident.”
The area in which they found the adenocarcinoma is called the ampulla of Vater. Everything in this part of the body is pretty small and overlapping so pancreatic cancer could be an explanation. But given my age and, let’s face it, the taboo around death, no one was talking about that.
When pressed, the doctor told me ampullary cancer, which has a higher survival rate and is still incredibly rare for someone my age but less rare than pancreatic cancer in the same age category.
Treatment
Discussing the Treatment Plan
Because of the size and the layout of this part of the body, they do the Whipple procedure, also called the pancreaticoduodenectomy. They do the same surgery for ampullary cancer as they do for pancreatic cancer.
Five days after the phone call, I was in his office and he said, “I’m going to remove part of your pancreas and part of your small intestine.” I didn’t have a gallbladder, but that also would have gone including part of my stomach.
My surgeon told me that they cut me open and, contrary to what they thought, found a tumor on the head of my pancreas that had spread outside of the pancreas. Metastatic pancreatic cancer is considered inoperable so when they saw that, they closed me up.
Because of my age and because they suspect that I’m a BRCA2 mutation carrier, the surgeon said, “We have to confirm with genetic tests, but I’m pretty sure you have this particular genetic abnormality. If that’s the case, then there are targeted therapies that might work for you.”
He said, “This is a mean cancer. But because of your particular situation, after treatment, we might be able to try the surgery again in a year.” For pancreatic cancer, surgery is the only long-term survival solution. Chemotherapy and radiation are life-extending, but they’re not curative. He was pretty confident, at least in the context of a lethal diagnosis.
Later that day, he introduced me to my oncologist. He was not as confident. When pressed, he said, “With treatment, you might have 1 to 3 good years left, but that’s it.”
FOLFIRINOX Chemotherapy
This was at the beginning of May 2021. My wound had to heal. Three weeks later, I started chemotherapy. Like a lot of other people with metastatic pancreatic cancer, I was given FOLFIRINOX, which is five different drugs. It’s awful. Chemo combinations are all awful, but FOLFIRINOX was really, really abrasive.
I had a scan after three months on FOLFIRINOX. The oncologist said, “Your tumor shrank a little bit,” but you can tell from the way he’s telling me that it could be an imaging error or a minute retreat that it’s barely perceptible.
At my next CT and MRI three months later, the tumor grew. It had metastasized to my liver so things were not looking good. At this point, I was not confident that I would be a special case or a miracle. I thought this was it.
Switching Chemotherapy Regimens
My oncologist switched me to a different chemotherapy combination. He told me there was a combination that some researchers found was promising for people in my situation. It was gemcitabine, nab-paclitaxel, and cisplatin (GAP).
I was honestly relieved because after being on FOLFIRINOX for almost six months, the neuropathy had gotten so bad that I couldn’t get out of a chair by myself. I needed someone to hoist me up. I was pretty thin at this point. It was miserable.
On the new chemotherapy regimen, my quality of life improved dramatically. By the time my first set of scans came around three months in, some of the spots on my liver had started to disappear. I did three more months of chemo and made it through.
I didn’t lose my hair. I’m six feet tall. I was 215 lbs when I was diagnosed and miraculously maintained a healthy weight so I’m very thankful for that. At this point, I thought I was still dying sooner rather than later so I was trying to have fun and it certainly made having fun a lot easier.
Post-Treatment Scans
In March 2021, he looked at my scans and, if memory serves, they could not identify cancer outside of the tumor.
Almost a year to the day, they attempted to do the Whipple and, this time, it was successful. When Dr. Allen came into my hospital room, he said all of my margins were good and the lymph nodes they tested were negative.
Before this, they couldn’t see any cancer on the CT or MRI, but that didn’t mean that my peritoneum wasn’t covered in cancer. That just meant that they wouldn’t be able to tell until they got in there. They were pleasantly surprised that things had worked.
Follow-up Protocol
The last scan was a lot smoother than the others, but they’re incredibly difficult. I get a scan every three months for the next six years, but the chances of me living out those six years are astronomically small. Pancreatic cancer has a remarkably low five-year survival rate. It’s unlikely that I will see all of that time, at least on paper.
Words of Advice
It’s important to remember that you are not a statistic. I was diagnosed with something I wasn’t supposed to have at my age. It was very unlikely. It was supposed to kill me and I didn’t die so, in a sense, I beat the odds not once, but twice.
People think that pancreatic cancer is an old person’s disease. I think that’s why no one ever looked because no one ever even thought that I could have pancreatic cancer. I’ve heard over and over again that I’m too young. Statistically speaking, they’re correct. For people under 35, it’s incredibly rare, but there is a difference between statistical analysis and what statistics are for, and encountering a patient one-on-one.
Treatment is not linear. Pancreatic cancer is often thought of in linear terms as a quick, short trajectory to death. We assume that if treatment will work, it will work immediately. You don’t take one step back and one step forward. In my experience, that’s not true. Sometimes things get worse before they get better and it’s not a reason to lose heart.
Have a drink, eat the cheeseburger, and live your life to the extent that you can. That’s how I lived. Take your health seriously but also meet yourself where you are.
Symptoms: None; found the cancers during CAT scans for internal bleeding due to ulcers Treatment: Chemotherapy (capecitabine + temozolomide), surgery (distal pancreatectomy, to be scheduled)
Cancer Details: Found after Galleri blood test and MRI 1st Symptoms: None Treatment: 5FU (folfirinox), Gemzar, NK cell expansion therapy, Dendritic cell expansion therapy, Neoantigen peptide vaccine
In this discussion, patient advocates Cindy Chmielewski and Jack Aiello speak with multiple myeloma experts, Dr. Rafael Fonseca with Mayo Clinic and Dr. Susan Bal with University of Alabama at Birmingham. They discuss the latest coming out of the 2023 American Society of Hematology meeting and share the latest multiple myeloma clinical trials and treatment options.
Learn about new multiple myeloma treatment options, including triplet and quadruplet combination therapies, CAR T-cell therapy, bispecific antibodies, and trispecifics. Find out about the future of belantamab mafodotin (BLENREP), dose reduction of dexamethasone, and the introduction of sonrotoclax, dubbed as the next-generation venetoclax.
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: I’m the founder of The Patient Story and, more importantly, I also got a blood cancer diagnosis of non-Hodgkin lymphoma a few years ago.
We have so many shared experiences in what we’re looking for and that’s what The Patient Story is all about.
I want to give special thanks to GSK for supporting our educational program. Their support helps programs like this more available and free for our audience. We want to note that The Patient Story retains full editorial control of this entire program and this is not meant to be a substitute for medical advice.
Our patient moderators Cindy Chmielewski and Jack Aiello will lead this conversation. Cindy and Jack, can you share a little bit more about your own stories and how you became such passionate advocates in this space?
Cindy Chmielewski, Patient Advocate
Cindy Chmielewski: I’ve been living with multiple myeloma since 2008. What brought me to the doctor was very debilitating back pain. The pain was so bad that it affected my job. I was having a hard time standing up to teach. I wasn’t able to take my class to the playground for recess. I had to have other teachers do that.
I went to an orthopedic doctor who, unfortunately, I think was unfamiliar with the symptoms of multiple myeloma because he diagnosed me with degenerative disc disease. It took an additional two years to get the correct diagnosis.
Since then, I’ve had several treatments and I’m now doing very, very well. I’m excited because I’m hearing all these new therapies that will be available to me if and when I relapse.
Jack Aiello, Patient Advocate
Jack Aiello: I was diagnosed with multiple myeloma at the beginning of 1995.
It started with a backache but MRIs and X-rays didn’t show anything wrong according to a specialist I went to see. I ended up taking a blood test and that showed an elevated protein. The specialist said I likely have multiple myeloma and that was the start of about eight years of significant treatment.
Back then, the average life span for myeloma patients with treatment was only 2 to 3 years. I was fortunate to respond to a third transplant except that I used donor stem cells after a couple of earlier transplants and clinical trials didn’t work for me.
I’m extremely appreciative to be alive 29 years later. I think this discussion is awfully important as all of these webinars are for myeloma. In particular, we focus on what happened at the 2023 American Society of Hematology meeting that will affect patients immediately as well as where the research is going. I’m always in favor of making sure I understand what’s going on so that I can help myself if my disease comes back and I can help others when I’m leading our support group or talking with other patients.
Rafael Fonseca, MD
Cindy: Dr. Rafael Fonseca is a hematologist-oncologist at Mayo Clinic with a special interest in multiple myeloma. He also participates in and leads clinical trials that have led to the approval of various drugs for the treatment of myeloma
Dr. Fonseca, what drew you to multiple myeloma, and what drives you most to continue to work in helping myeloma patients?
Dr. Rafael Fonseca: The way I got into myeloma is a little bit of luck but mainly because I had great mentors. The late Dr. Philip Greipp was a wonderful influence. I wanted to do lymphoma, but he steered me into myeloma without knowing what would happen. Those were the days of melphalan and prednisone, which links exactly to what drives me now.
We are very fortunate to be living through these times when so many things are happening in the treatment of myeloma. One of my colleagues, Dr. Ruben Mesa, told me a few years back that we are either a drug away or a combination away from being able to cure a significant fraction of patients. We’re shuffling the pieces on the table, but I think we’re there so that keeps us going every day.
Dr. Bal, what drew you to myeloma, and what drives you most to continue your work to help patients?
Dr. Susan Bal: Myeloma was always very exciting to me personally. I started my fellowship the year that we saw the first results from daratumumab come about.
Other than the excitement in the field and the possibility of a cure, one thing that drives me most is the meaningful relationships that you can continue to build because our patients live for so long and do so well.
I’m so delighted to be able to work with a great group here and across the country. The myeloma community is strong and we forge onward in our path to curing this condition.
Patients can come to us from any of these avenues and that’s what makes it interesting… It’s a very heterogeneous disease, certainly in terms of presentation and how people do overall.
Dr. Susan Bal
Overview of Multiple Myeloma
What is Multiple Myeloma?
Cindy: Briefly, what is multiple myeloma and what are some of the first signs and symptoms?
Dr. Bal: Multiple myeloma is a plasma cell disorder so it’s plasma cells that have become cancerous. We have white cells, red cells, and platelets. White cells fight infections, red cells carry oxygen, and platelets stop us from bleeding.
Symptoms of Multiple Myeloma
Dr. Bal: One of the types of white cells that help us fight infection is the plasma cell. The plasma cell is responsible for making antibodies that normally help us fight infection.
Sometimes when these plasma cells go awry and become cancerous, they can crowd out the bone marrow, resulting in symptoms such as elevated calcium levels, bone breakage, and bone damage. It can affect our kidney function, causing renal dysfunction. It can also cause low blood counts because of crowding out of the marrow.
Because it’s a part of the immune system and its job is to prevent infections, oftentimes, patients can present with recurrent infections as a presenting feature as well.
Patients can come to us from any of these avenues and that’s what makes it interesting. We see patients who are simply diagnosed because they had an astute primary care physician who picked up on a protein gap. We have patients presenting on the other end of the spectrum with the plethora of all symptoms that we know as CRAB symptoms, presenting with very disabling features. It’s a very heterogeneous disease, certainly in terms of presentation and how people do overall.
As is true with everything else in medicine, the availability of additional information has allowed us to narrow down the best options for patients.
Dr. Rafael Fonseca
Considerations When Choosing Treatments for Different Patient Groups
Cindy: Dr. Fonseca, we’re lucky now that there are so many treatments available. When I was diagnosed back in 2008, the treatment arsenal was not nearly as filled as it is now.
What are some of the considerations you think about when choosing treatments for different groups, like transplant-eligible versus transplant-ineligible and newly diagnosed and high-risk? What goes through your mind?
Dr. Fonseca: That’s the essence of everything we do in the practice. All of those considerations and how we present them and share them with patients as options for their treatments.
When we started seeing all these drugs come forward and being approved, my first reaction was, “Boy, this is going to get complicated. How are we going to choose? We have all these treatments. My appointments may have to be two hours long because I have to present everything to patients.”
As is true with everything else in medicine, the availability of additional information has allowed us to narrow down the best options for patients. Even though we have many more drugs, we still have 1, 2, or 3 options that are probably the best for a person at a given step. That has allowed us to work more on our messaging and the rationale of what we do.
The considerations you mentioned are critical. We always want to look at, first of all, the patient as a person with their preferences and goals, as well as some other health issues or comorbidities.
One of the critical aspects — and one we can’t modify though I know many wish we could — is our age. Age is a major determinant of how well you’re going to be able to tolerate treatment or not.
Some treatments become quite a bit toxic as we take them later on in life. A great example of this is the stem cell transplant. As physicians and clinical teams, we have to tailor our approach to patients as we start proposing the various treatments.
The second consideration is whether the patient is newly diagnosed or someone who, unfortunately, has myeloma that’s coming back or what we call recurrent myeloma. If we think about that, then we say: which stage is this? Is this an early recurrence or is this someone who has already received 3 or 4 prior lines of therapy?
Then we bring other factors that are important for patients to know about and we discuss them with the patients. We test the myeloma cells for genetic makeup. When we talk about genetics in myeloma, we’re mostly talking about the changes that occur in the myeloma cells, not the genetics that a person may have in the rest of their body and, very importantly, not genetic things that are passed on from generation to generation.
Those are things that play into our decision-making process. Some patients have markers that would make us more concerned, something we call high-risk myeloma. With that in mind, we put together treatment plans that we propose to our patients.
We’re moving forward with a more unified approach to goals. If you go back 15 years or certainly, in 1995, our goal was to control. Can we do something that will put the myeloma at bay that would allow us to gain time?
Many of us feel like the pendulum has swung completely in the other direction. Many individuals, myself included, think that we should aim to eradicate all myeloma cells and, ultimately, produce cures for patients. How you phrase that and plan for that becomes important. Behind that, there’s a whole set of other principles. Those are some of the overriding things we think about but always starting with the patient.
We were lucky to have two major presentations at the meeting, including a plenary session where we saw results from the IsKia trial, as well as a late-breaking session where we saw results from the PERSEUS trial.
Dr. Bal: The American Society of Hematology meeting is a key event for hematologists. It’s where we expect to see some of the latest and greatest of science and all the discoveries and innovations that are occurring within the field. It’s a one-stop shop where we get to see some of the best data so it’s a very looked forward to event in the community.
This ASH was no different. We were lucky to have two major presentations at the meeting, including a plenary session where we saw results from the IsKia trial, as well as a late-breaking session where we saw results from the PERSEUS trial.
The PERSEUS study was perhaps one of the most awaited trials in the sense that this was a randomized phase 3 trial evaluating a quadruplet regimen of daratumumab, bortezomib, lenalidomide, and dexamethasone versus the same combination without daratumumab in patients with newly-diagnosed, transplant-eligible multiple myeloma. For many in the field, we have moved towards using these quadruplets based on an earlier phase 2 randomized GRIFFIN trial. This was practice-affirming and perhaps practice-changing for a small proportion of patients in the community.
What this trial did was take patients who were transplant-eligible — who are fit and in the European and Australian countries where this was predominantly performed — and were randomized into receiving four drugs versus three drugs followed by stem cell transplant and then a doublet maintenance following consolidation therapy with the same regimen.
Overall, what we saw was with a close to four-year follow-up, patients who received this four-drug regimen did a lot better and had longer progression-free survival at the four-year time point. Patients had a very deep response with this regimen achieving measurable residual disease negativity, both using very sensitive markers and sustaining over prolonged periods, which has been shown to be hopefully a surrogate for improved patient outcomes overall.
Within the US, many in the field have already taken up the practice of adopting this four-drug regimen based on the prior GRIFFIN study, but I think this was confirming and affirming for those of us who are doing that and practice-changing for those who were still using the triplet combination. This was perhaps one of the most exciting things to come out of this trial, among other things.
Jack: That’s fantastic. Dr. Fonseca, what about you? Can you describe an outcome you saw from ASH that was so important to the myeloma community?
Depending on how you measure and what the threshold is, we have studies showing that somewhere between 60 and 80% of patients can get into minimal residual disease.
Dr. Rafael Fonseca
Dr. Fonseca: What Dr. Bal described is the crux of what we saw at the 2023 ASH meeting. This is our key meeting where we see all this data.
No one would be surprised if we tell you we actually have a lot of fun being at that meeting because we’re with friends. We work the longest hours that we work in the year. Sometimes it’s hard to convince our family that it’s work because we’re all smiling, talking, and exchanging ideas, and then we go for dinner and discuss further.
It’s a wonderful time for us and more so given the progress we’re seeing in myeloma. The fact that we now have very strong data for what needs to be done in the front line is very important for patients.
At this moment, it’s beyond any doubt that we need to use the best treatments up front. For now, that means the incorporation of anti-CD38 monoclonal antibodies. Dr. Bal mentioned the use of daratumumab. We also have a similar molecule, isatuximab.
The clinical trials point to outstanding results, which could not be seen ever before in the treatment of myeloma. The results are so good that they’re now going to start challenging some of our assumptions.
We had the meta-analysis for the maintenance strategy for myeloma, where patients go through induction, get the transplant, and are placed on maintenance. But Dr. Luciano Costa has pointed out repeatedly that those maintenance studies were done where we could achieve a complete response in about 30 to 40% of patients, minimal MRD negativity, and sometimes patients were getting two drugs as induction.
One would say it was no surprise that more treatment was effective. Whether we call it maintenance or consolidation is semantics. Now we’re getting to the point where many patients have a complete response. Depending on how you measure and what the threshold is, we have studies showing that somewhere between 60 and 80% of patients can get into minimal residual disease.
We’re starting to ask: do you even need maintenance in those patients? I don’t claim in any way that we have the answers, but it reflects how fast things are moving forward. Breaking it down, as Dr. Bal did, is critical.
For some people, we were practicing this, but for other people, either they need this for regulatory purposes across the globe or their reading of the medical literature is such that they want to have that phase 3 trial before they change clinical practice.
Right now, it would be rare that a patient would not be offered induction therapy with something, as we were describing. A lot of things are getting simplified. In a conversation with colleagues, I said the treatment of myeloma should always start with something like daratumumab, lenalidomide, and dexamethasone.
The secondary question is whether the patient needs to get a proteasome inhibitor, like bortezomib or carfilzomib, and whether they need to get a transplant. But then things get simplified because the best players rise to the very top of what we’re doing so I’m excited for what this means for patients.
Dr. Bal: I completely agree with Dr. Fonseca. I feel like some things are almost becoming cleaner as we go. I remember this discussion about three years ago where everybody wanted to know: would you give daratumumab to a transplant-eligible patient? The answer is becoming clearer and clearer that you want to use your best drugs upfront and make that first cut your deepest.
Recently, somebody asked me, “Is there a patient whom you would not give daratumumab to?” I said, “I don’t know who that would be because it’s such a well-tolerated, effective therapy.” Now I’m thinking more like what Dr. Fonseca said about which of the other agents you could potentially get rid of or improve upon, rather than the daratumumab.
I’m not saying we’re ready to dispense with transplants, but the data continues to show that deep responses, no matter how you get there, will result in better outcomes.
Dr. Rafael Fonseca
Front-Line Therapy for Transplant-Eligible Patients
Jack: Dr. Fonseca, one of the important trials — and Dr. Bal referred to it earlier as having been given special recognition at ASH as a plenary session — was the IsKia clinical trial, which compared carfilzomib, lenalidomide, and dexamethasone, adding isatuximab to it or not as front-line therapy for transplant-eligible patients. Isatuximab is like daratumumab in that they’re both CD38 monoclonal antibodies. It was another four-drug trial. Can you talk a little bit about that?
Dr. Fonseca: The reason something is given that plenary status is when the reviewers and the reviewing committee feel that there is something of such high value that reaches the high standards of evidence or that even potentially becomes immediately practice-changing.
This particular clinical trial was one more point in that direction where they started looking at the response rate and the MRD negativity rate for those patients. MRD negativity refers to measurable residual disease or minimal residual disease, which is nothing different than saying we have better markers to assess the depth of a response through mechanisms such as genetic testing.
It’s becoming increasingly clear and very well-documented that achieving the status where you can no longer find measurable disease — using very sensitive tools where some can go at the level of detecting one cell out of a million — becomes a harbinger of great outcomes for patients, of durable responses, and ultimately improvements in the various metrics that we call survival. The IsKia trial shows that.
It’s very interesting to me for a couple of reasons. This is a different antibody, a different molecule than daratumumab, but the presumption by those in the field has been that we should see similar results. These antibodies carry nothing of what we call a payload. They’re a naked antibody so they go and bind to those cells. By doing that, they unleash our immune response to those cells. They’re able to kill more cells. We know that because the responses are better and the MRD is better.
In that particular trial, we have to wait a little bit longer to see over time what the outcomes will be on those metrics that people hear about, like progression-free survival and overall survival. But given what I said about MRD, all the indicators are that this will be a very useful approach for the treatment of patients.
Everyone should get a CD38, like lenalidomide and dexamethasone, at least for the time being. But then the question is: what about these drugs that we call proteasome inhibitors? In this particular trial, they used carfilzomib. For me, that’s very interesting because that’s what I do in my clinical practice.
When we make decisions in our clinical practice, there are trade-offs. Carfilzomib is a sister medication of bortezomib. They’re both proteasome inhibitors, but each one has different toxicities.
There’s no clear-cut evidence that one is better than the other, but I don’t like the enduring toxicity that occurs with some of the other drugs, like bortezomib. That’s where we will be spending our time, talking about those types of drugs. Should we use bortezomib or carfilzomib? Both are standard of care and excellent treatment. There are nuances of why we choose one or the other.
There will be the question of transplant, too. If you have these regimens that can make patients have such a great response that they become “MRD negative,” the question will come forward: do you even need a transplant?
I’m not saying we’re ready to dispense with transplants, but the data continues to show that deep responses, no matter how you get there, will result in better outcomes. Maybe some patients will elect to say, “I’m going to collect cells and think about a transplant later.” That’s a very long, nuanced conversation but a reflection of the progress we’re making with this type of combination.
In terms of which proteasome inhibitor is the right choice, some of that depends on the patient’s profile, comorbidities that they already have, and age.
Dr. Susan Bal
Triplet and Quadruplet Regimens
Cindy: Dr. Bal, you were saying that things are becoming cleaner, but now, we’re thinking about four drugs upfront, but which four drugs? Dr. Fonseca was alluding to it, but are there any considerations that you take into whether your proteasome inhibitor is going to be bortezomib or carfilzomib, or what CD38 monoclonal antibody to use? What goes through your mind now that you’re picking four drugs?
Dr. Bal: As Dr. Fonseca mentioned, the patient in front of you helps determine some of that. As you know, daratumumab and isatuximab are both anti-CD38 monoclonal antibodies. They are both very effective drugs.
However, one is subcutaneous so administration is a little bit easier with daratumumab, which is given as a short injection underneath the skin. The other one requires an IV. For now at least, until we have the subcutaneous version for isatuximab, I do believe that reduces share time and and patient inconvenience very much.
In terms of which proteasome inhibitor is the right choice, some of that depends on the patient’s profile, comorbidities that they already have, and age.
For example, with bortezomib, we’re aware that the risk of peripheral neuropathy is significant and can be quite disabling even at lower grades. However, with carfilzomib, we have seen cardiac and renal toxicities. Even more than just objective data, a lot of people complain of subjective dyspnea and subjective shortness of breath, which can make it challenging for them to feel good during treatment.
Young, very robust, and perhaps high-risk patients are best stratified into the carfilzomib arms, and older patients, depending on their fitness, would then get either no proteasome inhibitor or a bortezomib-based option.
That part is rather individualized, without any clear data of one being overly more efficacious than the other, at least based on the data that we do have in front of us.
In very elderly, very frail patients, daratumumab is exceedingly both efficacious and quite safe, as long as you provide them with appropriate antibiotic coverage, close monitoring, vaccination, and perhaps even IVIG use to protect them from infections.
Dr. Susan Bal
Possibility of Quadruplet Treatment as Standard of Care
Cindy: Are there particular patients that you would not give the quadruplet regimen to, where you would probably go back to triplet therapy or maybe even doublets?
Dr. Bal: Incorporating frailty assessment and assessment of the patient’s overall performance status going beyond the eyeball test that we do is going to be critical in determining who is not fit to receive a quad.
In cases where there are concerns about the use of a proteasome inhibitor, particularly bortezomib, due to underlying diabetes or other comorbidities or the patient’s age and you’re concerned about cardiopulmonary toxicity with carfilzomib, as Dr. Fonseca also mentioned, daratumumab with lenalidomide and dexamethasone is an excellent option with high-level evidence of benefit.
I would say for very old patients who are in their high 80s, even 90s, I would consider a doublet. What’s interesting is that the doublet I would consider would be a dara-dex type of combination or even single-agent dara because IMiDs require hematopoietic monitoring or blood work closely checked for low blood counts. The proteasome inhibitors carry all the concerns that we mentioned.
In very elderly, very frail patients, daratumumab is exceedingly both efficacious and quite safe, as long as you provide them with appropriate antibiotic coverage, close monitoring, vaccination, and perhaps even IVIG use to protect them from infections.
Does everyone need maintenance? I don’t know what the answer to that is yet, but I know that the question is very relevant.
Dr. Rafael Fonseca
Cindy: Dr. Fonseca, do you have anything to add to what Dr. Bal said? What about maintenance? Are you seeing single-drug or double-drug maintenance?
Dr. Fonseca: I want to emphasize one of the points that Dr. Bal made. If you asked me two years ago what I would do with a frail patient who has newly diagnosed myeloma, my response would have been lenalidomide and dexamethasone. However, we saw with the subset analysis in the context of the MAIA clinical trial that the addition of daratumumab significantly improved outcomes for these patients.
I’m glad we have the data because we would be at significant risk of shortchanging patients in the line of thinking of beneficence. Let’s be kind. Let’s use mild treatments. But it turns out that the survival numbers are not as good.
Now, whenever we add a drug, we have to think whether we’re adding toxicity, but the reality is these antibodies are incredibly well-tolerated. It’s different to propose adding carfilzomib or not versus adding daratumumab. Today, I would say the vast majority of patients, even if they’re frail, should get something like daratumumab upfront.
Maintenance is really, really interesting. I’m hoping and I think we’re going to get there soon. Studies, like the ones done by the group of Dr. Bal, are using these adaptive strategies to look at whether we can stop therapy, which naturally leads to the next question. Does everyone need maintenance? I don’t know what the answer to that is yet, but I know that the question is very relevant.
We’re going to get to the point where we’re going to think of maintenance like people think of adjuvant therapy for breast cancer. You complete the surgery. They look at the lymph nodes and the genetic makeup of breast cancer and say whether you need chemotherapy or not. As we incorporate our genetic knowledge, the status of response after induction plus or minus transplant, then we are going to ask those questions.
Does everyone need maintenance? I think it’s going to diverge a little bit more to the extremes. There’s going to be greater contrast. For patients who have standard risk genetic factors, are able to complete induction therapy, have a transplant, and have MRD negativity 10-6, it’s going to be hard to prove that maintenance would have an added benefit. If so, hopefully something that’s better tolerated because, as we know, lenalidomide has significant burden toxicities for patients.
On the other hand, if the patient has residual disease, I don’t think there’s a good enough reason to say that’s what we do. That’s standard. I’m going to cross my fingers and wish that this is not going to come back. I think those are patients for whom we’re going to provide additional treatment for no other reason than to try to get rid of all residual myeloma cells.
I think that’s where we’re going to go with maintenance. I don’t foresee that maintenance, as we have it right now, where everyone gets lenalidomide. You get it until you can tolerate it and hopefully not have side effects or no disease progression. I think that has to change.
If you can eradicate evidence of disease, you can improve your outcomes significantly.
Dr. Susan Bal
Dr. Bal: I couldn’t agree more. We certainly share our opinions regarding the use of measurable residual disease. It’s become the single most important prognostic marker, one that is not defined at all when you’re first diagnosed but comes into play after therapy.
If you can eradicate evidence of disease, you can improve your outcomes significantly. Whether you’re starting as a high-risk patient or a standard-risk patient, getting to that milestone and, more importantly, maintaining that milestone can improve outcomes.
I think maintenance as we know it today will soon cease to exist, hopefully, but mostly because we’re either giving them more therapy, getting them where they need to be, or they’ve done so well because of the excellent therapies we have that we don’t need to continue suboptimal treatments that have other toxicities and risks associated with them.
In the lab, we essentially teach these cells using a viral vector to express receptors on their surface that can target cancer antigens within a patient’s body.
Dr. Susan Bal
CAR T-cell Therapy
Jack: As effective as the treatments are, myeloma still often comes back and one of the exciting new treatments going forward is CAR T-cell therapy. Dr. Bal, can you explain what CAR T-cell therapy is in conjunction with what you presented at ASH?
Dr. Bal: CAR T-cell therapy stands for chimeric antigen receptor T-cell therapy. Within our bodies, there are immune cells and one of those subtypes is T cells, which are normally working to keep our cancers in check. The thought is that these T cells are not working as well as they need to be and the cancer itself is finding mechanisms to evade our immune system, which is what results in disease relapse.
CAR T-cell therapy is a revolutionary therapy. We take out a patient’s T cells by apheresis, very similar to a procedure that patients go through when they do stem cell collection. In the lab, we essentially teach these cells using a viral vector to express receptors on their surface that can target cancer antigens within a patient’s body.
Thereafter, we provide the patients with lymphodepletion chemotherapy, which is essentially chemotherapy that’s given to reduce the number of T cells which are within the patient’s body. We then infuse these chimeric antigen receptor T cells, which go and interact with the antigen, using their CAR receptor, and cause cancer killing or tumor death.
This has been shown to be a very effective modality, particularly in patients who previously haven’t had very good treatment options after they’ve been through the three main pillars of therapy, like CD38 monoclonal antibodies, immunomodulatory agents, and proteasome inhibitors. These patients previously had dismal outcomes measured in single-digit months. Now with these therapies, they’re living longer and having excellent responses, including several that are MRD negative even in late-line disease settings.
At this time, there is FDA approval for two chimeric antigen receptor therapies in myeloma that target the B-cell maturation antigen. This is an antigen that is present on the surface of plasma cells in general and more on the surface of malignant plasma cells or cancer cells. Using this target, we have seen very impressive responses of up to 98% overall responses with one of the FDA-approved agents, known as cilta-cel. This is shown to be an effective avenue.
What we presented at the 2023 ASH meeting is a chimeric antigen receptor T-cell therapy that targets a different antigen known as GPRC5D. This antigen is also one that is expressed preferentially on the surface of these cancer cells and has limited expression across normal tissues, although we do see some expression on tissues such as heart keratinized tissues, on the skin, on nail beds, and in hair follicles. We see some typical side effects, including dyskinesia, with treatments that target this therapy.
Overall, GPRC5D has been shown to be a promising therapeutic target in myeloma. We already have a different immune strategy that’s working against this and is FDA-approved.
In this phase 1 study, we evaluated a CAR T cell that is targeting GPRC5D in patients with relapsed myeloma. What we saw is that in a heavily pre-treated patient population who have received a median of five prior lines of therapy, this was associated with deep responses overall. In about 73 patients who were efficacy available, meaning were available for response assessment, we saw that 88% of the patients had a response.
For the first time, we shared the recommended phase 2 dose, which is the dose that’s going to be moving forward. It was determined at about 150 million CAR T cells. What was encouraging was that the response rate for this recommended phase 2 dose was 91%. At that dose level, we saw low-grade CRS. No patient had grade 3 or higher CRS. There were no cases of other serious toxicities, such as macrophage activation syndrome, etc. This dose was efficacious.
So far, the follow-up for this dose cohort is relatively short so we don’t know what the long-term progression-free survival and overall survival are going to be. But the responses are deep. We need to follow the study longer to understand the more important and relevant outcomes, like progression-free survival and overall survival.
If they work well downstream, as is true for every single myeloma drug, we keep bringing them towards the forefront. The results are quite remarkable.
Dr. Rafael Fonseca
Jack: Dr. Bal mentioned that there are a couple of approved CAR Ts available for patients now, except for the fact that they require four-plus lines of prior therapy.
There are trials and announcements of results from those trials, like CARTITUDE-4 and KarMMa-3, that are testing these same CAR T-cell therapies in earlier lines of treatment. Can you talk about the results in relation to a patient’s quality of life?
Dr. Fonseca: I think that is probably the key aspect of all of this. As you mentioned, two trials are looking at CAR T-cell therapy earlier on: KarMMa-3 with 2 to 4 prior lines of therapy and CARTITUDE-4 with 1 to 3.
What they explored is if they work well downstream, as is true for every single myeloma drug, we keep bringing them towards the forefront. The results are quite remarkable. Many of you saw the presentations and ultimately the publication of the CARTITUDE-4, which was presented at ASCO as well as EHA and published in the New England Journal.
What we’re seeing is this treatment can provide very durable responses that can go on for years for some patients. Then, of course, the natural question is: how does this compare to other treatments? We have effective treatments that can work very well in someone who is experiencing a first relapse, such as the combination of daratumumab, carfilzomib, and dexamethasone or isatuximab, carfilzomib, and dexamethasone.
But the one big advantage of CAR T-cell therapy is that it’s “one and done.” We’re seeing patients who are reporting very high levels of quality of life and making statements like, “I haven’t felt this well in such a long time.” It’s not because CAR T-cell therapy gives you superpowers. It gets rid of all of the side effects that come with treatment.
Even the most benign of treatments involves logistics, medications, blood draws or venipuncture, and some have side effects that come from the chemicals or the biologics that are used. Even in the best-case scenario, it’s something that the patient has to do. The idea that you’re done and all that needs to be done is occasional labs to monitor becomes very appealing.
I think that’s probably going to be the number one driver. Of course, we’re very excited. We’re hoping to see these treatments have very, very long-lasting benefits for some patients. But even if they were not, for some, the ability to be treatment-free would be beautiful.
I always quote our colleague, Dr. Amrita Krishnan from City of Hope. She said that one of the unmet needs in myeloma is to stop therapy so even if it’s temporary, for some hopefully more durable, this would be a way to achieve that.
Jack: I have patients in my support group who say exactly what you say. Some are without treatment three years after their CAR T-cell therapy but even those who relapsed sooner, like within six or ten months, say they would do it all over again because they had that drug-free period that they were so appreciative of.
We know that patients, after having the CAR Ts, can sometimes have prolonged periods of low blood counts and no one really knows why.
Dr. Rafael Fonseca
Side Effects of CAR T-cell Therapy
Jack: That said, Dr. Fonseca, I want to ask another question about a specific CAR T-cell therapy side effect having to do with secondary myeloid cancers, like acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). I’m hearing some concerns about that and wonder what your take is on what’s out there.
Dr. Fonseca: First of all, I’m going to say that we don’t completely understand this and many other factors may come into play.
The FDA recently put an announcement that a fraction of patients, up to 10% in the series that was reported, could develop secondary myeloid malignancies. These are the cells that produce your regular white cells and the conditions that follow from that are either leukemia, acute leukemia, or the preceding stage, which we call myelodysplasia, which is concerning as well to us as physicians.
There are many reasons why this could be nothing more than the reflection of patients living longer and patients who have had exposure before to a number of agents and drugs that are clearly known to cause this. This could include things such as melphalan, which is used for stem cell transplant, but also some of the drugs that are used for the priming of the body for CAR T cells, including fludarabine.
On the other hand, there might be other reasons why this could be linked to CAR T-cell therapy. You’re going to hear more about this as people do the research. For instance, we know that patients, after having the CAR Ts, can sometimes have prolonged periods of low blood counts and no one really knows why.
For instance, in the case of BCMA. BCMA is predominantly expressed in B cells, not in these myeloid cells. How come we have myelosuppression? We don’t know for sure. But if you have that, then there are a lot of hypotheses that can come forward. Does that create an environment that maybe selects for clones that are going to do this? Does that create an inflammatory situation that maybe allows for the progression of some of those pre-malignant clones?
The threat is much greater from unattended myeloma. While we want to have perfect treatments with no side effects, for someone who’s considering CAR T-cell therapy, it’s much better to get it than not, despite these considerations.
Dr. Rafael Fonseca
Our audience is familiar with the term MGUS (monoclonal gammopathy of undetermined significance). As you know, we have myeloma and you have MGUS, and this is a prototype of this stepwise progression. It turns out there’s a similar thing that happens for myeloid cells that there’s something called CHIP (clonal hematopoiesis of indeterminate potential) and it turns out to be very common. It’s one of the things that happens to all of us in life as we age. You develop these premalignant states and CHIP is very common. It can be seen in up to 40% of people.
The question is: what are the CAR Ts doing that maybe makes some of this CHIP grow more or the CHIP cells be favored? We don’t know, but this is an important question.
But practically speaking, as of now, the threat is much greater from unattended myeloma. While we want to have perfect treatments with no side effects, for someone who’s considering CAR T-cell therapy, it’s much better to get it than not, despite these considerations.
Jack: They have other options, like bispecific antibodies.
One of the best parts about bispecific antibodies is the fact that you don’t have this lag time or delay that comes with manufacturing associated with CAR T cells.
Dr. Susan Bal
Bispecific Antibodies
Cindy: Dr. Bal, I hear patients sometimes refer to bispecific antibodies as off-the-shelf CAR Ts and I know they’re not. Can you explain the difference between a bispecific antibody and a CAR T?
Dr. Bal: Bispecific antibodies are antibody fragments. I typically describe them to my patients as a little Y-shaped linker. This is an antibody with two prongs if you will. On one hand, it uses the CD3 molecule to catch the T cell and on the other hand, it has an antigen receptor for one of the myeloma targets.
Currently, we have bispecific antibodies that target cancer cells using the same antigens that we talked about for CAR T-cell therapy, such as B-cell maturation antigen (BCMA) or GPRC5D. They target the cancer cell using one of these antigens and bring the two close so that cancer cell killing by the immune system can occur.
One of the best parts about bispecific antibodies is the fact that you don’t have this lag time or delay that comes with manufacturing associated with CAR T cells. These therapies are off the shelf. They utilize the patient’s own T cells, bring them close to the cancer cells, and result in cancer cell killing.
Oftentimes, where we don’t have the time or the manufacturing capability or the slot allocation, or all of those patients who are not necessarily being treated at a large center with CAR T-cell capabilities, this provides an avenue to use new immune treatments and immunotherapies for a wider range of patients. It has the potential to reach many more patients, given the current state of affairs, at least in 2023 and 2024, and so presents a very exciting option for our patients.
Some could argue they don’t have as of yet the same horsepower as some of the CAR Ts. Many of us are thinking of using them down the line, but some of them in combination are incredibly, incredibly active.
Dr. Rafael Fonseca
ASH 2023 Updates on Bispecific Antibodies
Cindy: Dr. Fonseca, were there any major updates on bispecifics at ASH 2023 that we should know about?
Dr. Fonseca: We had a number of updates from some of the longer-term outcomes and some of the studies that are looking at bispecifics in various combinations, including with some of the traditional agents. I’m very interested to see how this plays out.
What we’re seeing is that bispecifics, first of all, are very active. Some could argue they don’t have as of yet the same horsepower as some of the CAR Ts. Many of us are thinking of using them down the line, but some of them in combination are incredibly, incredibly active.
There are clinical trials looking at bispecifics in combination with pomalidomide, bispecifics between themselves, and bispecifics with daratumumab in combination. There’s a trial that combines talquetamab and teclistamab, the RedirecTT-1 trial.
We have new constructs that are being developed. We saw a presentation about something called a trispecific so instead of having one side that a bispecific can attach to, there are bispecifics that could attach to two different anchor points that these myeloma cells have.
Now, I’m particularly interested in bispecifics because the possibility that many more patients be treated is there for bispecifics than for CAR T-cell therapy. CAR T-cell therapy requires centers of excellence and referral patterns, and there are wait times for cell production. Whereas with the bispecifics, they’re “off the shelf.”
It’s going to take some time. People have to become familiarized with this, but in the future, we’ll see community hospitals and mid-sized hospitals administering these bispecifics, which in my mind is wonderful because many more patients will derive benefit from this type of therapy.
This is the beginning of a new era in cancer treatment because solid tumors are being explored for bispecifics so lung cancer might be treated with this. Oncologists in the future will certainly need to be facile and comfortable with the use of bispecific antibodies.
There’s a lot of push for fixed-duration therapy. One of the greatest reasons, beyond patients having to come to the hospital or clinic and the treatment and travel burden, is the side effect profile.
Dr. Susan Bal
Dosage & Administration of Bispecific Antibodies
Cindy: Dr. Bal, can you talk about the dosing and schedule of bispecifics?
Dr. Bal: Currently, three FDA-approved bispecific antibodies are on the market. We have two agents targeting BCMA: teclistamab and elranatamab. Both target the B-cell maturation antigen. As of right now, these drugs are typically given on an ongoing basis until disease progression or unacceptable toxicity.
Typically, these start in the hospital with a small portion of inpatient hospitalization. Patients receive step-up dosing to minimize the risk of certain side effects. Afterward, they go on to weekly or every two weeks. In this fashion, they go on until the patients continue to respond or come off due to side effects.
However, patients take a median of a little over a month to respond to these agents and up to about six months to get into a complete response. Often, these responses are very deep. In patients who go off treatment because of side effects, we see that some of these patients can maintain their response for years without treatment.
There’s a lot of push for fixed-duration therapy. One of the greatest reasons, beyond patients having to come to the hospital or clinic and the treatment and travel burden, is the side effect profile. These B-cell maturation antigen-directed bispecific antibodies have a lot of infection risk.
Seventy-plus percent of patients get infections and 40 to 50% of these can often be grade 3 or higher, which can be quite serious. These infection risks, particularly oftentimes infection with unusual things that we don’t typically see in myeloma patients, have also enhanced some of our concerns about using these agents on a prolonged basis in patients whose disease may be controlled.
Multiple factors are at play so there’s a lot of interest in studying fixed-duration therapy of these agents to tailor it to a patient’s response and be able to discontinue these therapies once they’re responding to optimize their risk and benefit profiles.
We know that when we use several agents that target the same anchor, there is a possibility that you could develop resistance so we’ll have to wait and see.
Dr. Rafael Fonseca
Antibody-Drug Conjugates
Cindy: Dr. Fonseca, we talked about CAR T-cell therapy and bispecific antibodies. Let’s talk about antibody-drug conjugates. We had one that was approved through accelerated approval and then taken off the market but now it may be back. Could you talk about BLENREP (belantamab mafodotin)?
Dr. Fonseca: Antibody-drug conjugates are antibodies that carry a payload. There’s usually a chemical entity attached to an antibody. In general, what happens is the antibodies bind to the cell surface and go inside the cell. They’re eaten into the cell where they release that chemical structure.
One of those antigens is belantamab. When it first started, it showed very, very high rates of response. Quite promising responses. It went through regulatory approval for a fast-track approval.
Unfortunately, there had to be a confirmatory phase 3 trial that did not meet the endpoint. That means that the data for the trial would not support the complete approval by the FDA. The product has been since withdrawn from the market but is available on a compassionate basis.
This is a highly active compound. It comes with some baggage. One of the main baggage is toxicity to the eyes. Something we call keratopathy and that’s inflammation of the outside layer of the eye, the cornea. As we’re learning how to use it in better doses, that has been a little bit better tolerated. It’s not to say it doesn’t exist, but people are understanding better how to use this.
We learned about two very exciting trials. One of them is the DREAMM-7 trial, which was belantamab, lenalidomide, and dexamethasone versus daratumumab, lenalidomide, and dexamethasone. We’re told the trial is positive meaning there are favorable effects of the belantamab. We’ll have to see what the actual numbers show.
There’s another one that was recently published called the ALGONQUIN clinical trial, which is a combination of belantamab, pomalidomide, and dexamethasone, which has pretty interesting results.
The question is going to be: how do we time all of this? Belantamab targets BCMA as well, too, so that means it could compete with bispecifics and CAR Ts. We know that when we use several agents that target the same anchor, there is a possibility that you could develop resistance so we’ll have to wait and see.
ADCs are one of the hottest things right now in biotech and development for solid tumors as well, too. I heard from people who were at one of those recent conferences that a lot of companies are interested in them. I think we’ll see a comeback of ADCs in myeloma and in other diseases as well, too.
I have patients right now who are still enjoying the benefits of the prior administration of belantamab.
Dr. Rafael Fonseca
Cindy: Do you think Blenrep will be coming back on the market?
Dr. Fonseca: It’s interesting. I’m not currently up to date on what the regulatory pathway will be for that to occur. I think it will, but the results are exciting. The question is how this will compare to some of the other things that I’m mentioning with bispecifics.
I have patients right now who are still enjoying the benefits of the prior administration of belantamab. They have since resolved the eye toxicity. In all cases, with time, the eye toxicity improves. These are patients that may have gotten a short course of treatment with belantamab and remain under excellent control right now.
It’s always better to have more options. I don’t think I would venture out to say exactly how we’re going to sequence this because of the issues of resistance, but I certainly would welcome having that back in our toolkit.
Cindy: I agree. More options are better because we’re also unique and what works for one person may not work for somebody else so I’m glad to have as many bullets in our arsenal as possible.
BCL2 inhibition has a place and hopefully, we’ll find FDA approval soon so we can use it more freely and benefit this unique subset of patients.
Dr. Susan Bal
BCL2 Inhibitors for Myeloma
Jack: Dr. Bal, venetoclax is well-known out there. It’s an approved drug for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), but it gets used off-label in myeloma patients who have a translocation called t(11;14). At ASH, something called sonrotoclax was introduced as the next-generation venetoclax. Do you have any comments about that particular new drug?
Dr. Bal: Translocation t(11;14) myeloma is a subtype of myeloma that’s a little bit of a different disease itself. It’s a distinct entity and a distinct subtype of myeloma, which responds a little bit differently to different agents. It has a higher dependency on BCL2 inhibition, which is a key part of what drives this myeloma and, therefore, inhibiting it in this space helps drive treatment responses.
We know venetoclax is an effective therapy. Unfortunately, the randomized trials have not worked very much in favor of it. However, those of us who use it and single-arm studies have shown impressive responses in this subset of myeloma patients.
At the ASH 2023 meeting, we looked at a novel BCL2 inhibitor, which is supposed to be at least 10 times more effective and more selective for BCL2 inhibition. It’s called sonrotoclax and they are studying it in a phase 1 setting in several countries. They’re looking to first get the right dose and then expand it in combination with carfilzomib to best understand how these patients respond.
We know venetoclax is an effective therapy. Unfortunately, the randomized trials have not worked very much in favor of it.
Dr. Susan Bal
What we have seen at ASH 2023 was a result from about 19 patients, 10 of whom got the recommended phase 2 dose, which is going to move forward in studies. What we saw was very impressive single-agent activity in combination with dexamethasone at the recommended phase 2 dose of 70%.
What was even more impressive to me was the complete lack of dose-limiting toxicities. There were really minimal side effects that would prevent dose-finding and dose escalation, and a very low risk of low blood counts, which was something that we thought we would see.
The drug was very, very well tolerated. I recall maybe a single patient with high-grade diarrhea and maybe a COVID-19 infection, which was ongoing during the study. Overall, the safety profile is very impressive with responses in combination with dexamethasone of 70% at the recommended phase 2 dose. As the study accrues more patients and studies combinations with carfilzomib, I think it will be exciting.
I will also touch on some of the data that was presented by Dr. Bahlis, which was venetoclax in combination with daratumumab, which showed very impressive responses. Although the patient population was less heavily pre-treated and mostly daratumumab-naive, response rates and measurable residual disease negative states were very, very impressive. BCL2 inhibition has a place and hopefully, we’ll find FDA approval soon so we can use it more freely and benefit this unique subset of patients.
The long-term use of dexamethasone is not contributing much to the control of the disease and we know for sure it’s contributing to the burden of side effects.
Dr. Rafael Fonseca
Dexamethasone Dose Reduction
Jack: Dr. Fonseca, we patients always appreciate it when we learn that doses can be reduced. When we hear that dexamethasone dosing can be reduced, we get giddy about it.
At ASH 2023, there was a presentation that looked retrospectively at a couple of SWOG trials, S0777 and S1211, which looked at patients who had lower dex dosage. Can you talk about that and what that might mean for patients going forward?
Dr. Fonseca: Whenever we discuss treatments with a patient, I usually emphasize that the hardest part is probably going to be the dexamethasone, for reasons you know better than I do. It all started several years ago with a patient, Michael Katz, who said, “We get too much dexamethasone. What can you do about that?” That led to the design of E4A03, which changed our paradigm that we now use dexamethasone at what we call “low doses.”
When my endocrinology friends see those doses, they tell us, “What are you doing? This is a massive dose of dexamethasone.” That was a significant change. We used to use 12 days per cycle, that is 12 out of 28 days at 40 mg of dexamethasone.
We’ve moved forward but have not completely gotten rid of it. From what we know now, as you go on with treatment, as shown by the studies mentioned, as the patient gets stabilized, it becomes increasingly clear that the long-term use of dexamethasone is not contributing much to the control of the disease and we know for sure it’s contributing to the burden of side effects. It should be noted that several studies are showing that. Clinicians need to be cautious and need to adjust the doses of dexamethasone.
In the beginning, most of us feel that patients need a little bit of dexamethasone to “jump start” a good response. But even then, you can do some dose adjustments. In patients of more advanced age, we often will use 20 mg instead of 40 mg. As well, in patients who have amyloidosis, we’ll make adjustments like that.
Is there a way by which we can tell who is going to benefit from the addition of the steroids?
Dr. Rafael Fonseca
It’s important to be mindful of this because patients should not be on 40 mg of dexamethasone once a week for a long time. In general, this is not something that we should be using long-term for maintenance. It can be used short-term for consolidation or other reasons.
The field continues to move in that direction. One patient once asked me, “You always talk about lenalidomide resistance, but you never say dexamethasone resistance. How do you know if it’s contributing down the line?” That is one question that we need to go back and address.
At the beginning of myeloma drug development, there were a lot of people who were interested in resistance to steroids, like Dr. Steve Rosen from City of Hope, and we abandoned that line of thinking. We need to go back and say: is there a way by which we can tell who is going to benefit from the addition of the steroids?
Sometimes, myeloma is very aggressive and very difficult to control. But please don’t assume that because you’re facing this diagnosis, there’s an imminent threat that for sure will be life-limiting because the treatments continue to get better.
Dr. Rafael Fonseca
Final Takeaways
Cindy: If you had one key takeaway that you want patients to hear, what would it be?
Dr. Bal: For me, the most exciting thing in myeloma right now is immunotherapy. The prospect of these new agents that use our immune system to kill cancer cells is really innovative and exciting. I can’t wait to understand how best we can use these strategies to provide fixed-duration treatment and lead to the longest possible remission in a low or undetectable cancer state, such that our patients can have an excellent quality of life.
Dr. Fonseca: We’re very excited and positively so because of the developments in myeloma. We fully realize it would be better to meet you in social circumstances or at coffee somewhere else. But right now, if you’re diagnosed with myeloma, for many, many patients, there are options such that myeloma should not be an immediate threat.
In fact, for many patients, we develop this relationship, as Dr. Bal was saying, and then we track along with you for years and even decades for some patients. It’s not unusual for us to see patients in the clinic well beyond 10 years, sometimes 15 and 20-plus years. I am convinced some of those patients have been cured because of effective frontline therapy. But even for those who haven’t, there are often times options for treatment.
Unfortunately, I know this is not a reality for everyone. Sometimes, myeloma is very aggressive and very difficult to control. But please don’t assume that because you’re facing this diagnosis, there’s an imminent threat that for sure will be life-limiting because the treatments continue to get better.
Jack: For any myeloma patient and care partner, stay educated. There are so many new treatments coming so quickly for myeloma and they are for different target audiences: newly diagnosed as well as relapse patients.
One way to stay educated is to listen to programs like this. Check out the myeloma advocacy websites that offer webinars and videos. Join a support group and make sure to understand the best questions to ask your doctor.
Cindy: It’s important for patients to be seen by a myeloma specialist. Anytime a patient has to have a treatment decision to make, it’s imperative that they get guidance from a myeloma specialist. There are so many new treatments available, new data being presented on different treatments that are now coming to market, and clinical trials so it’s overwhelming.
Conclusion
Stephanie: Thank you so much, Jack and Cindy, for being our incredible patient advocates and moderators. Also to Drs. Fonseca and Bal for the work and research you do to help move the landscape of treatment options in multiple myeloma.
We hope that you walk away with a better understanding of the latest treatments and clinical trials in myeloma. They may or may not be right for you, but it is our goal to make sure you feel empowered to make a decision for yourself.
Thank you and we hope to see you again at a future program at The Patient Story.
Special thanks again to GSK for its support of our independent patient education content. The Patient Story retains full editorial control.
Where is Hodgkin lymphoma headed in 2024? Two-time Hodgkin’s lymphoma survivor Dr. Sam Siegel discusses with top lymphoma experts, Dr. Natalie Grover of UNC Health and Dr. Stephen Ansell of Mayo Clinic, as they break down what patients and caregivers need to know!
Key topics include the latest treatment options and clinical trials, reducing toxicity from treatments, advances in post-transplant relapse, and the roles of CAR T-cell therapy and bispecific antibodies in the treatment of Hodgkin lymphoma.
Thank you to Pfizer 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, the founder of The Patient Story. I also got a blood cancer diagnosis a few years ago. Mine was non-Hodgkin lymphoma, but we have so many shared experiences in what we’re looking for and that’s what The Patient Story is all about.
We help both patients and care partners navigate a cancer diagnosis. We do this primarily through in-depth conversations with patients, care partners, and top cancer specialists.
I also want to give special thanks to Seagen for supporting our educational program. Their support helps programs like this become more available and free for our audience. We want to note that The Patient Story retains full editorial control of this entire program and that this is not meant to be a substitute for medical advice.
Our patient moderator, Dr. Sam Siegel, will be leading the conversation from this point forward.
Sam Siegel, MD, Patient Advocate
Dr. Sam Siegel: Thanks, Stephanie! I’m a two-time Hodgkin’s lymphoma survivor, bone marrow transplant survivor, and primary care physician doing survivorship medicine. I’m here to have this wonderful conversation with Dr. Natalie Grover and Dr. Stephen Ansell about Hodgkin lymphoma updates.
Natalie Grover, MD
Sam: Dr. Natalie Grover is a hematologist-oncologist at the UNC School of Medicine. She’s the clinical director of the cellular therapy program, leads several CAR T-cell therapy clinical trials in lymphoma, and strives to improve treatment options and quality of life for lymphoma patients.
Dr. Grover, can you tell us a little bit about yourself, what drew you to lymphoma, and about your approach to patients and how you care for them?
Dr. Natalie Grover: I was drawn to oncology as a maternal medicine resident. Much of it was based on my relationship with patients whom I saw in the inpatient oncology ward. When I saw those patients, I always wanted to go back and find out more about what happened to them and form connections with them.
There were so many discoveries and new treatments available. Even during residency, the treatment landscape was changing so much and that drove me to oncology.
I like how heterogeneous lymphoma is and how it involves a wide patient population of both young and older patients. It’s truly a systemic disease. There are so many different types of lymphoma so my clinic is a very heterogeneous mix of different patients and I enjoy that.
Sam: That makes a lot of sense. Lymphoma is the umbrella, but it’s a lot of different diseases that can affect multiple parts of the body. I could see how that’s interesting.
Stephen Ansell, MD, PhD
Sam: Dr. Stephen Ansell is a hematologist-oncologist at the Mayo Clinic who studies and specializes in Hodgkin’s lymphoma. His research has led to the use of immune checkpoint therapy in lymphomas, which is a very exciting development. His goal is to translate his research into new treatment approaches.
Dr. Ansell, can you tell us about your path into lymphoma, what drew you to the field, and your approach to patients?
Dr. Stephen Ansell: I trained in South Africa. I was very focused on internal medicine, but they needed someone to do some work temporarily in oncology and assigned me.
When I got there, similar to Dr. Grover, I was excited about the opportunity, the disease, the patients, and how we could make a difference based on the fact that treatments were highly effective and beneficial. Patients benefited substantially even from initial treatments back in the day of more chemotherapy.
What has been exciting for me throughout my career has been to see how we can change treatments by increasing the number of people who benefit and hopefully get cured, and decreasing the side effects and toxicities by being able to find effective therapies that aren’t that hard on patients.
Sam: Your areas of interest and passion are so personally meaningful to me and my lymphoma journey, and I think will resonate with a lot of people.
Even though I had some side effects from the brentuximab at the highest dose that I first started it on, it still felt like a cakewalk compared to my initial drug regimen.
Dr. Sam Siegel
Sam’s Hodgkin Lymphoma Story
Sam: I was diagnosed with stage 2AE Hodgkin’s lymphoma and the reason that 2AE is important is because E means extranodal manifestations. I had some lung involvement and it was confusing whether or not I was a stage 2 with right around the lymph nodes in that lung or stage 4. That was going to impact how many months of chemotherapy I would have.
I started with ABVD chemotherapy. Within two months, the initial cough that I had at the time of diagnosis improved pretty quickly. Towards the end of those two months, I started getting a cough again. My PET scan looked good so the thought was that bleomycin was probably to blame for that cough.
We dropped bleomycin and it felt pretty okay making that decision. I suspected that something else was going on, but because the scan had come back clean, we decided to watch and wait.
About a month or two after that, I developed symptoms that were eerily reminiscent of my initial diagnosis, such as wheezing in the upper left side of my chest, which I knew wasn’t normal, and a pea-sized lump above my collarbone in a very similar location to where the initial lump was.
I suspected that those were Hodgkin lymphoma symptoms and sought care right away. The PET scan showed that I was most likely having a relapse.
It was a process to get the tissue to confirm the relapse. I had to have three biopsies, with the third one involving a thoracic surgery to get a lymph node right near my heart.
By that time, I felt so beaten up by traditional cytotoxic chemotherapy. New information was coming around about salvage therapy, which is the therapy after a person has relapsed from initial therapy. At that time, I didn’t feel that I could go through another few months of multi-drug traditional cytotoxic chemotherapy.
Data was coming out about brentuximab, an antibody-drug conjugate, and using that as a bridge to autologous bone marrow transplant. My oncologist said, “These trials showed that this could be an effective bridge to transplant. What do you think?” I said yes because I wanted to go for the therapy with the least amount of toxicity.
Even though I had some side effects from the brentuximab at the highest dose that I first started it on, it still felt like a cakewalk compared to my initial drug regimen.
That goes to show how important the science is and the clinical trials that inform oncologists how to adjust therapies, especially therapies that were traditionally pretty toxic in terms of long-term and late-term effects.
There are always ways in which we’re trying to make treatment better… we’re trying to replace radiation therapy by utilizing new agents.
Dr. Stephen Ansell
Standard of Care: First-Line Treatments
Sam: Dr. Ansell, can you tell us about the current standard first-line treatments and their efficacy for Hodgkin lymphoma?
Dr. Ansell: In many respects, we think about it in two buckets: people who have more limited-stage disease (only on one side of the diaphragm, either above or below) or advanced-stage disease (both sides of the diaphragm, in the bone marrow, or other tissues).
With limited-stage disease, we again think of two buckets. These are different symptoms and other tests to determine prognostic factors. If you have favorable prognostic factors, we treat you with very minimal chemotherapy. If you have more symptoms and unfavorable factors, we will treat you with a little bit more treatment. If you have advanced disease, we give you more treatment yet again.
There are always ways in which we’re trying to make treatment better, but the most standard way is if you have very limited disease with good favorable factors, we often will give two rounds of chemotherapy treatment and then consider consolidation radiation treatment.
If you have a more advanced disease, still limited to one side of the diaphragm but with more unfavorable factors, we would give more chemotherapy and more radiation treatment. Then for advanced-stage disease, we would give chemotherapy and no radiation treatment.
However, we’re trying to replace radiation therapy by utilizing new agents. We’ve used PET scans to tell us who might need extra treatment or not. I have to hedge a little bit because a lot of it is individualized and that’s the most important thing.
It’s so important to raise awareness about the importance of being involved in clinical trials and knowing that you don’t have to have failed multiple lines of therapy before you consider them.
Dr. Sam Siegel
Sam: Absolutely. How do you decide? There are different prognostic systems so if somebody is unfavorable in one and favorable in others, how do you factor that in?
Dr. Ansell: Pick one system and utilize the data supported by that system. The German Hodgkin Study Group has done a lot of work in this space. In our practice, we tend to use the prognostic system that they use because that helps us standardize treatment.
What we want to do is always push the envelope. We encourage people to participate in clinical trials that are testing new ways compared to the standard ways to see if we can optimize treatment even further.
Sam: I love that. Thank you for bringing up clinical trials. It’s so important to raise awareness about the importance of being involved in clinical trials and knowing that you don’t have to have failed multiple lines of therapy before you consider them.
Clinical trials can be for everyone and there are so many different types of situations where somebody could need a clinical trial. We’re looking at things to de-escalate therapy or alter treatments based on a patient’s situation.
Dr. Ansell: I would say you’re exactly right. The most impressive and important data that has come out on Hodgkin lymphoma is in the front line based on recent clinical trials. Everyone needs to remember that what we do currently is based on people who have participated in clinical trials that have changed how we practice.
Standardly, we utilize new agents, like PD-1 blocking antibodies or brentuximab vedotin plus chemotherapy, rather than chemotherapy alone because that’s improved the outcome of patients. Especially in advanced-stage patients, that’s now the standard of care.
The two biggest drugs that have transformed the care for Hodgkin lymphoma in the past 5 to 10 years are brentuximab vedotin… and checkpoint inhibitors.
Dr. Natalie Grover
Latest Advancements in Treatments
Sam: Dr. Grover, what are some of the newest and hottest treatments for Hodgkin lymphoma?
Dr. Grover: I think the hottest advances in Hodgkin lymphoma are related to incorporating some of these new treatments into earlier lines of therapy to try to both improve outcomes so increase the chance of cure and reduce long-term toxicities.
The two biggest drugs that have transformed the care for Hodgkin lymphoma in the past 5 to 10 years are brentuximab vedotin, which is an antibody-drug conjugate. It delivers chemotherapy specifically to the cancer cells.
The cancer cells in Hodgkin lymphoma have a marker on them—CD30—that’s pretty much universally seen in all the Reed-Sternberg cells, the cancer cells in Hodgkin lymphoma. Brentuximab specifically targets those.
The other drugs are what people may have heard of called checkpoint inhibitors. These immunotherapies help the immune system fight Hodgkin’s lymphoma.
When they incorporated these drugs—nivolumab, pembrolizumab, and brentuximab—they were successful in relapsed/refractory disease. Now they’re being moved to earlier lines of therapy to try to reduce the amount of chemotherapy that we’re giving patients and hopefully to enhance care in these patients.
By limiting chemotherapy and radiation, can you improve patient outcomes?
Dr. Natalie Grover
Sam: How about some recent clinical trials for reducing toxicity? I heard about AHOD2131.
Dr. Grover: There’s a clinical trial for pediatric and adult patients looking at whether we can incorporate these newer treatments, brentuximab and checkpoint inhibitors, in newly diagnosed Hodgkin lymphoma patients.
Everyone gets two cycles of standard chemotherapy then patients get randomized to either getting these new treatments, brentuximab and nivolumab, or continuing to standard chemotherapy.
The question is: by limiting chemotherapy and radiation, can you improve patient outcomes? One thing they want to look at is cure rates and long-term survival from a Hodgkin’s standpoint, but they’re also collecting data looking at quality of life patient-reported outcomes.
The top priority is curing their lymphoma, but we also want to think about the quality of life for patients moving forward and making sure that they live long lives.
Dr. Natalie Grover
Sam: That’s incredible. When you’re talking about late-term effects or reducing toxicities, what are some of the things that we’re trying to reduce long-term?
Dr. Grover: One of the chemotherapy drugs that we give patients can affect their heart function so some of the things that we think about are the risk of heart disease down the line.
One of the drugs that we’re using a lot less often now can affect lung function so we look at issues with lung function past therapy.
With some of these drugs and using more brentuximab, another thing that we’re thinking about is neuropathy. Patients can have some nerve damage and issues with pain, numbness, and tingling or doing different functions, like texting, typing, or writing.
With young patients, another thing we think about is fertility. Even though many of these patients can have children in the future as a lot of these earlier treatments don’t have as big an effect on fertility, it’s still something we think about, especially if we need to escalate people who have a disease that relapses or need more aggressive therapies.
We also think of secondary cancers. Some chemotherapy and radiation may increase the risk of having other cancers.
The positive is that most of these patients live long enough for us to focus on that and think about these effects. The top priority is curing their lymphoma, but we also want to think about the quality of life for patients moving forward and making sure that they live long lives.
Checkpoint inhibitors help the immune system fight the cancer. Some of these patients may stop responding to checkpoint inhibitors so there’s interest in using other types of treatments in combination.
Dr. Natalie Grover
Sam: What about trials to re-sensitize to PD-1 drugs? What does that mean?
Dr. Grover: Checkpoint inhibitors are effective in Hodgkin lymphoma. Right now, we’re moving them to earlier lines of therapy but these are treatments that can also work well for relapsed and refractory patients.
Hodgkin lymphoma is unique because, compared to other lymphomas, there aren’t that many cancer cells in these patients. When pathologists look at cells, there are a lot of immune cells around the cancer cells so there aren’t that many lymphoma cells. A lot of it is your immune reaction to the lymphoma.
Checkpoint inhibitors help the immune system fight the cancer. Some of these patients may stop responding to checkpoint inhibitors so there’s interest in using other types of treatments in combination. If a patient progresses on pembrolizumab or nivolumab, can you combine them with other treatments and re-sensitize your immune system so they can be sensitive again to these treatments? There’s some research looking into that.
We’ve also seen patients get the reverse. These treatments may reset the patients in some way. Patients may get checkpoint inhibitors and then after that may respond better to other treatments. There have been some studies showing that after checkpoint inhibitors, even if they progress on those drugs, patients potentially respond better to chemotherapy or other treatments.
Sam: We’re still learning how these drugs impact the immune system and how they might make you respond better to traditional chemotherapies, even if you didn’t initially. That’s incredible.
Dr. Grover: The current biggest advances are in advanced-stage Hodgkin lymphoma. More recently, brentuximab was incorporated in addition to chemotherapy. Dr. Ansell was part of that study. That improved overall survival in advanced-stage Hodgkin lymphoma patients compared to standard of care.
We can see the progression from old-style chemotherapy to immune checkpoint plus chemotherapy as the front-line treatment.
Dr. Stephen Ansell
Early vs. Advanced Stage Advancements
Sam: Dr. Ansell, can you tell us about the SWOG S1826 trial and what that showed?
Dr. Ansell: Picking up again on the theme of better therapies getting better outcomes and using some of the new drugs that we’ve touched on, as Dr. Grover said, the management of advanced-stage patients has moved over time.
Back in the day, we gave ABVD chemotherapy and tried to leave out bleomycin, which causes lung toxicity, if patients were doing well based on PET scans.
These new drugs, brentuximab vedotin being the first one, were brought into the combination in place of bleomycin. It’s now brentuximab with AVD. When compared head to head, it showed that brentuximab improved the outcome of patients—not only their likelihood of staying in remission but their overall survival.
It was then compared as the standard to nivolumab, the PD-1-directed therapy, plus AVD chemotherapy in place of bleomycin. That then showed progression-free survival at a one-year follow-up. We don’t have mature data yet, but it seemed better already than the brentuximab-AVD chemotherapy and, as Dr. Grover touched on, less in the way of side effects and better tolerated.
That’s likely to become the new standard for advanced-stage patients. We want to see a little bit more mature data. But certainly, in elderly patients where toxicity is a real challenge, this has become a standard for many. We can see the progression from old-style chemotherapy to immune checkpoint plus chemotherapy as the front-line treatment.
Sam: These are exciting times. It’s wild because, for decades and decades, it seemed like we were doing the same thing for Hodgkin patients. Even if I were diagnosed with the same clinical scenario now compared to when I was first diagnosed in 2021, I would be treated differently.
There is still a subset of people where the disease proves to be very challenging and keeps relapsing… We still see patients who have gone through this standard treatment using these new drugs and then the disease comes back yet again.
Dr. Stephen Ansell
Gaps Clinical Trials are Filling
Sam: Can you tell us about these clinical trials and what gaps they fill?
Dr. Ansell: You heard us talk about two new drugs. They came from the relapsed setting but have moved up to front-line treatments. The gaps are for patients, heaven forbid, who have gone through these new therapies.
There is still a subset of people where the disease proves to be very challenging and keeps relapsing. That group’s getting to be smaller and smaller so that’s the good news. The challenging point is that it’s never good enough until there’s nobody in that group. We still see patients who have gone through this standard treatment using these new drugs and then the disease comes back yet again.
Things that are becoming exciting and that we need to do better on is what to do for those patients. Additional treatments that target these other immune checkpoints aside from PD-1 and other ways to make the immune system wake up and do its job are being tested.
The work that Dr. Grover and her team do is taking your immune cells, sending them to “training camp” to get a little docking site on them so they can detect the cancer in a much better way, and then unleashing them on the cancer. That’s proving exciting.
Finally, what we call bispecific antibodies. Those are also being tested and are some of the exciting opportunities in the future.
One arm of the antibody is directed to CD30, but the other arm grabs onto CD3 in the T cells.
Dr. Stephen Ansell
Bispecific Antibodies
Sam: Can you tell us about bispecific antibodies?
Dr. Ansell: This is an area that’s growing fast in Hodgkin lymphoma. Dr. Grover talked about CD30, which is on the cancer cells. One arm of the antibody is directed to CD30, but the other arm grabs onto CD3 in the T cells.
Bispecific antibodies bring those cells into very close proximity to each other. Like your kids in the back of the car who don’t like to sit next to each other and keep poking each other, this causes those cells to be grumpy with each other. The T cells, your immune cells, will then fight the cancer. That’s really what you want to see.
We talked about immune checkpoints that make T cells do a better job. One of the ways we’re doing that is on one arm, PD-1, which is an established immune checkpoint, but on the other, something like TIM-3, which is another immune checkpoint.
Other ways in which T cells are being switched off are now protected so it’s making those cells even more efficient. Those are two of the main ways bispecific antibodies are being tested right now.
With CAR T-cell therapy, we have seen some nice responses in patients whose disease has progressed after many different therapies, but there’s still work to do to improve these therapies.
Dr. Natalie Grover
CAR T-cell Therapy
Sam: Dr. Grover, how about CAR T-cell therapy and post-transplant relapses? Can you tell us about that and where CAR T-cell therapy might play a role?
Dr. Grover: As Dr. Ansell briefly mentioned, CAR T-cell therapy involves taking a patient’s T cells, sending them off, and re-engineering them so they can specifically target the CD30 protein on the cancer cell.
We have a CAR T-cell therapy trial at UNC and at the Baylor College of Medicine. There are two academic trials where we’re studying these CAR T cells in patients with Hodgkin lymphoma. There are also a few international trials. I know there’s a group in Spain and China.
Unfortunately, there isn’t a company-sponsored trial. They’re exciting treatments, but they’re not as easily accessible. Patients do need to travel for these for these treatments.
The big thing is long waiting lists, but we are hoping to get more patients treated more quickly because it still shows that there is an unmet need. Some patients have not responded, progressed after brentuximab, progressed after checkpoint inhibitors, progressed after transplant, and need additional options for treatment.
With CAR T-cell therapy, we have seen some nice responses in patients whose disease has progressed after many different therapies, but there’s still work to do to improve these therapies.
Right now, we have some patients who have been in remission for many years—five-plus years after getting CAR T cells. Many patients get the CAR T cells and have a great response, but their disease relapses afterward. We’re trying to figure out why that’s happening and how we can improve the CAR T cells and improve outcomes for patients.
Patients who relapse can have more aggressive disease as opposed to some other more aggressive types of lymphoma, but with Hodgkin, patients who have relapsed oftentimes can live a long time even with the disease.
Dr. Natalie Grover
Dr. Ansell: There’s one other option that takes both bispecifics and cellular therapies and combines those strategies. That’s taking the natural killer cells from cord blood and using a bispecific antibody that targets CD30 and a protein called CD16 on the NK cell. It sticks this bispecific antibody to the NK cell.
They pre-treat the NK cells before they give them to the patient and then infuse them. You activate the cells outside the body, add the bispecific antibody so that it’s already stuck to the NK cells, and infuse them. Those also have been effective therapies.
Dr. Grover’s right. We’re still learning about how many treatments you need to get. They’re getting high response rates, but the durability is still in question. But I think that’s another exciting strategy of taking cellular therapies and bispecifics and using them together.
Dr. Grover: I think that’s the LuminICE trial, which will be open at several different sites across the country.
Sam: That’s great. That’s an important point. It’s part of the issue of Hodgkin lymphoma compared to non-Hodgkin’s. It’s not nearly as common in terms of the number of people that will qualify for these trials so that may be why there are less commonly offered.
Dr. Grover: Hodgkin lymphoma has higher cure rates and is less common. A lot of times, patients who relapse can have more aggressive disease as opposed to some other more aggressive types of lymphoma, but with Hodgkin, patients who have relapsed oftentimes can live a long time even with the disease.
I’ve seen patients in my trials who have relapsed and have not even been in remission but have been living for many, many years with relapsed disease. A lot of times, these patients may not be as sick, which is a good thing, so they’re able to travel and participate in these trials. Many of these patients may be alive and doing well even though they’re going through treatment or have some disease left.
An allogeneic transplant is still a curative option and something that we would always consider.
Dr. Stephen Ansell
Transplant
Sam: Where is all this in relation to allogeneic transplants for people who are relapsing after transplant? Allogeneic, meaning the donor is somebody else, as opposed to autologous, which is more common in Hodgkin.
Dr. Ansell: To be honest, an allogeneic transplant is still a curative option and something that we would always consider. It’s a little bit high-risk because of the potential for longer-term toxicities.
With a lot of these novel treatments, many of which have been very successful in the past, people delayed allogeneic transplants a little bit. There are some challenges now as patients are having their disease come back after standard treatment so there is a subset of patients for whom that needs to be considered. That’s a very individualized discussion between patients and their doctors to weigh the risks versus the benefits.
One of the key questions to ask is what treatment somebody got as their first line because that impacts what you would do in the second line.
Dr. Stephen Ansell
Developments in Salvage Therapy
Sam: Dr. Ansell, what are some of the developments in salvage therapy, which is given when somebody has their initial relapse?
Dr. Ansell: It’s moving pretty fast right now. Novel drugs are being used in the front line so one of the key questions to ask is what treatment somebody got as their first line because that impacts what you would do in the second line.
However, based on where most patients are right now, not very many have had an immune checkpoint treatment, which is the nivolumab and pembrolizumab that Dr. Grover spoke about. Not too many people have had that as their front-line treatment and using those in combination with standard chemotherapies, like ICE chemotherapy or GVD chemotherapy. In the majority of particularly younger patients, going to more intensive treatment and a stem cell transplant using your own cells is very much the standard management.
Some interesting recent data compared where that was used to standard chemotherapy or the use of brentuximab and chemotherapy then a transplant and then looked at outcomes. The patients with the best outcome got a PD-1 antibody before they got their transplant.
Dr. Grover touched on this, which is an important point. The PD-1 blocking antibody team seems to change the immune system a bit and make patients more sensitive to some of the chemotherapies after the fact so that’s why it seems like it makes a difference. We tend to favor chemotherapy with immune checkpoint therapy as a treatment approach before going to transplant.
We want to see people cured. Heaven forbid that it comes back the first time, but if it does, all the gloves are off. Now we’re going at it as hard as we possibly can.
Dr. Stephen Ansell
Sam: That’s interesting because I know in other cancers, people will save therapies or not want to expose them because the body will learn them. What you’re saying is that the same principle may not apply in Hodgkin. These therapies may sensitize to other therapies or make people respond better so you don’t necessarily need to leave them until later when you’ve burned through other options.
Dr. Ansell: Correct. We want to see people cured. Heaven forbid that it comes back the first time, but if it does, all the gloves are off. Now we’re going at it as hard as we possibly can and we want to utilize all the effective tools that we have so that we can truly beat it into the ground. That’s what I would recommend. Different from other cancers where you might want to string things along in a palliative approach. With Hodgkin, you want to go after it with curative intent.
Sam: It’s wild to think how quickly things evolve and how important it is for patients to seek out providers or treatment at cancer centers who have some connection with the trials and know the latest updates.
How can we advise patients to seek out that kind of care? How can they ask for that from their oncologist if they’re getting treatment in the community?
Dr. Ansell: Be an informed patient. Ask questions and be a strong advocate for yourself. There are excellent resources, like The Leukemia & Lymphoma Society, which have good information related to many of these topics. Being informed about the best way to be managed is useful.
When your doctor sees you and goes through things, asking questions relative to the information that you have helps you feel reassured that you’re on the right track. Most of us are quite okay with patients getting second opinions from other colleagues.
Second opinions help people reinforce the messages you’re already giving. People will be more comfortable doing what needs to be done if they’re hearing the same thing from more than one person. All of that pertains to a good outcome. If you ask questions, make sure you get your questions answered.
Sam: Thanks for empowering patients because it’s so hard to make these decisions even when you have a lot of resources and education. It could be such an emotional time, in addition to not feeling well, and it’s helpful to hear that you expect people to want other opinions and be informed.
Dr. Ansell: To be honest, a lot of patients come in and get so much information that it’s pretty challenging to retain them. I always tell people to bring friends or family. Have other sets of ears that can help reinforce some of the messages so that when your brain is locked down and you can’t think straight, they hear things that you might have missed.
The treatments are getting better all the time so there’s a lot of hope. I’m hoping that in the not-very-distant future, every patient with Hodgkin lymphoma can be cured with front-line treatment.
Dr. Stephen Ansell
Final Messages
Sam: Dr. Grover, can you give us some final points or takeaway messages?
Dr. Grover: I’m excited about improving earlier therapies and moving these newer therapies to the front line both to hopefully enhance cure to prevent patients from relapsing again and reduce long-term toxicities and improve quality of life.
There’s still an unmet need for patients who are refractory to PD-1 inhibitors, brentuximab, and chemotherapy. I’m hoping that over the next few years, we will have more clinical trials and more developments for that patient population.
For patients, ask questions of your provider. Don’t be shy about getting a second opinion. I’m never offended if a patient goes for a second opinion.
Sam: How about you, Dr. Ansell?
Dr. Ansell: If you’re a patient with Hodgkin lymphoma, there are unique and novel treatments that are making a big difference to patient outcomes. The treatments are getting better all the time so there’s a lot of hope. I’m hoping that in the not-very-distant future, every patient with Hodgkin lymphoma can be cured with front-line treatment.
Sam: Thank you so much for that. I remember initially being scared about death and dying. I think that’s what a lot of people think about when they hear the word cancer. Once it began to move away from that and began to become living with cancer or living life after a cancer diagnosis, I thought, I’d like to jog, paint, play guitar, hold my kids, and be able to think as well as possible.
These trials to improve quality of life while simultaneously improving outcomes are so meaningful personally. I know it means a lot to our patient population that you took the time to have this conversation with us. Thank you so much.
Dr. Ansell: My pleasure.
Dr. Grover: Thanks so much for having us.
Stephanie: Thank you so much, Sam, for being our incredible patient advocate and moderator. Also, thank you to Dr. Grover and Dr. Ansell, for the work and research you do to help move the landscape of treatment options in Hodgkin lymphoma.
We hope that you walk away with a better understanding of the latest treatments and clinical trials in Hodgkin lymphoma. 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.
Thank you and we hope to see you again at a future program at The Patient Story.
Special thanks again to Pfizer for its support of our independent patient education content. The Patient Story retains full editorial control.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Raquel first noticed symptoms in 2019, like pencil-thin stools, pain, bloating, and blood in her stool. She then started getting full quickly after eating.
When she finally went to the doctor after developing severe pain, she was dismissed and told, “It was just anxiety.” She then ended up in the emergency room and was later diagnosed with stage 4 colorectal cancer, which had spread to her liver, ovaries, and lungs.
In sharing her story, she aims to raise awareness about rising colorectal cancer rates in young people and the importance of listening to your body.
In addition to Raquel’s narrative, The Patient Story offers a diverse collection of colorectal cancer 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.
Name: Raquel A.
Diagnosis:
Colorectal cancer
Staging:
4
Initial Symptoms:
Frequent bowel movements
Pin-thin stools
Mild red blood in stool
Treatment:
Chemotherapy: oxaliplatin, 5-FU (5-fluorouracil), and irinotecan
I feel so confident that whether I can heal from this or not, I’m going to be able to handle it well. It’ll be okay. I’ve overcome other things in life and I hope that I can be an inspiration to people who are struggling.
I’m 33 years old with terminal colorectal cancer. It has been such a huge part of my life that I have to remind myself that there are other parts outside of that.
I currently work in the tech industry and I’m very blessed to be able to do so.
In my spare time, I like reading and drawing. I’m very artistic and very recently, I’ve been posting more. I’ve been finding great connections on social media with other people who are going through the same thing as me.
I didn’t take my symptoms more seriously because they would come and go.
Pre-diagnosis
Initial Symptoms
I first started noticing symptoms in 2019. I was roommates with my best friend and she started to notice how often I was going to the bathroom. At the time, I was working in restaurant management so I figured I was probably eating too much of the food at work or eating too many processed foods.
I started changing my diet, trying to eat healthier and more protein but also using fiber supplements. I figured I wasn’t eating enough fiber and that’s one of the first things you read online about how to resolve diarrhea or bowel issues. That did help. The symptoms went away, but they would come back to plague me again.
Symptoms Worsened
In 2022, I was working as a contractor in the tech industry. I made really good friends with people on my team. One of them noticed how often I was going to the bathroom and she said, “Raquel, are you okay?” I said, “Yeah, I’m fine. Maybe it’s the dairy in my coffee. Maybe I have a gluten sensitivity.”
At the time, I wasn’t concerned and wrote myself off. I dismissed my symptoms. But knowing what I know now, I was having classic colorectal cancer symptoms.
I experienced frequent bowel movements and pin-thin stools. In addition, any kind of blood in your stool is a huge red flag. It means something is wrong. The color, whether it’s dark or mild red, pinpoints where exactly that bleed is located. Mine was mild red. I didn’t have heavy bleeding, which is why I thought there wasn’t something wrong.
But another classic sign is getting full quickly after eating and that was a huge red flag that something was wrong. That happened from 2022 until when I got diagnosed in May 2023. Every time I took a couple of bites of something, I immediately felt so bloated.
I was actively dieting before my diagnosis, but despite how healthy I was eating, I could not lose weight, which I thought was strange. My stomach was so round and hard. I would later find out that the cause of some of my bloating was ascites. When you have cancer that is as advanced as mine, especially with colorectal cancer, the tumors start secreting free fluid. I had about a gallon of fluid in my stomach that they had to drain. That immediately relieved so many symptoms I was having with eating.
I didn’t take my symptoms more seriously because they would come and go.
They’re not going to think of cancer when they see somebody who visually looks very healthy and young so I don’t necessarily blame her. At the same time, this dismissal of people who are like me is widespread because I know I’m not alone.
Symptoms Dismissed by Primary Care Doctor
It’s important to note that as a millennial—and I have statistically looked into this—half of us don’t have a primary care provider. That was the story of my 20s. I was blessed to land a permanent role in the tech industry where I had good healthcare and was able to schedule my first physical in 10 years back in May of 2023.
When you don’t go to the doctor for that long, there is a lot to talk about. I let my primary care physician know all of my symptoms, especially my bowel symptoms, and that I had severe abdominal pain somewhat recently. It wasn’t in one spot and felt very abnormal.
When I was talking to her about this, I could tell that she thought it was in my head. She scheduled me for a psychiatric appointment after my physical because she thought I had anxiety.
But now that I know so much about my disease, I know that they were classic colorectal cancer symptoms. Because I was so young, a woman, and a minority, statistically speaking, even just one of those categories is going to make you more likely to be dismissed in a medical setting and that is absolutely what I experienced.
It was maybe three weeks after that physical when my cancer was found to be completely metastatic and had spread all over. I know that she probably felt some guilt because, after my diagnosis, they sent the information to my primary care provider before I was assigned to an oncologist.
I’m sure once she saw how bad it was, she felt guilty at the same time. She’s not the only doctor who has done that, especially when you’re young. Medical doctors are taught these statistics of colorectal cancer being an older person’s disease. They’re not going to think of cancer when they see somebody who visually looks very healthy and young so I don’t necessarily blame her. At the same time, this dismissal of people who are like me is widespread because I know I’m not alone.
It wouldn’t be until I had a liver biopsy that they would find the primary source of my cancer, which was colorectal, and I wouldn’t find out until later how incredibly it had advanced.
Diagnosis
Getting the Cancer Diagnosis in the Emergency Room
I finally went to the ER. I remember that day so clearly.
I had severe abdominal pain that was migrating to my lower back and I almost fainted in my apartment. My intuition was saying that something was wrong so I went to the ER.
They did a full blood panel on me, which included the cancer markers CEA, CA 125, and CA 19. Mine were elevated. My CEA alone was in the 700s and anything above 30 is already a sign of cancer activity in your body. For mine to be that high means that my cancer was so advanced.
When I was in the ER, I felt that they took me seriously that’s why my cancer was found. The doctor knew something was wrong so she did that blood panel. I had an MRI, a CT scan, and an ultrasound. They did all those tests immediately.
The ER doctor told me that I had ovarian cancer because that’s where they found it initially. Based on the CT scan, the cancer was pretty advanced in my ovaries and my liver. It wouldn’t be until I had a liver biopsy that they would find the primary source of my cancer, which was colorectal, and I wouldn’t find out until later how incredibly it had advanced.
The metastases are in my colon, ovaries, liver, lungs, peritoneal cavity, and omentum. They found them through those tests within a week.
Everything happened so fast. I feel truly blessed that when I went to the ER, my cancer and the type of cancer was diagnosed so quickly. They ran all these tests, found my cancer, and immediately referred me to an oncologist. The next day, I was talking to an oncologist who then referred me to have a liver biopsy. A couple of days later, they found the primary source of my cancer.
Even though it’s very, very unfortunate how late my cancer was found, what an incredible experience for them to take me so seriously and find out what was going on. Kudos to the hospital that I went to. They took me very seriously.
Reaction to the Diagnosis
I don’t think I reacted like a normal person would have and that’s because I’ve had a lot of things happen in my life. I have a very calm demeanor. When things go wrong, I’m your go-to person to think logically and that’s how I processed my cancer diagnosis.
Even the doctor seemed really surprised that she said, “Raquel, you’re not even crying. I’m so sorry I’m not telling you good news.” I said, “You know what? It’s okay because no matter what happens, I’m going to get through it.”
I feel so confident that whether I can heal from this or not, I’m going to be able to handle it well. It’ll be okay. I’ve overcome other things in life and I hope that I can be an inspiration to people who are struggling. I feel like everything’s going to be okay. I told myself that even at the beginning of my diagnosis.
My liver and lung metastases aren’t responding to chemo, but the metastases in my ovaries and colon are responding moderately well. My oncologist and I are trying to see what combination could help with wherever else my cancer is.
Treatment
The treatment protocol and how they’re going to approach your diagnosis depends on your hospital. When I first got diagnosed, I was at a different hospital but for insurance purposes, I had to switch to a different one.
My treatments would have been a little bit different if I stayed with the first hospital because they wanted to start surgeries right away. They said, “You’re going to have a full hysterectomy. I’m going to be doing this in collaboration with one of our very renowned liver surgeons and we’re going to do this at the same time.”
But then when I switched to a different hospital, they told me, “We’re going to focus on chemotherapy. Let’s see how you react, shrink what we can, and then talk about surgery.” I understand the reasoning for that because they want to shrink as much as they can to lessen things going wrong during surgery or make it a little bit less risky.
Because I ended up switching hospitals, I’ve just been primarily I’ve been chemotherapy.
Being on Chemotherapy for Life
I first started with oxaliplatin. The side effects are not pleasant. It causes neuropathy. Fortunately for me, we stopped that in December. I was on it for six months until the side effects started affecting my quality of life too much.
I have switched to 5-FU (5-fluorouracil) and irinotecan. They introduced irinotecan to see if that’s going to help my liver metastases because so far, I’m having a mixed response to chemotherapy.
My liver and lung metastases aren’t responding to chemo, but the metastases in my ovaries and colon are responding moderately well. My oncologist and I are trying to see what combination could help with wherever else my cancer is.
I have chemotherapy bi-weekly and for Christmas, I pushed back my chemotherapy because I didn’t want to be sick during the holidays. My CEA, one of my cancer markers, jumped when I wasn’t strictly on my bi-weekly regimen. If I ever stopped chemotherapy, decided I didn’t want to continue, or changed my protocol at all, my cancer would jump at that opportunity to be aggressive.
I don’t have a choice as of right now. Chemotherapy is keeping me alive so I’m going to continue being on it bi-weekly. Fifty percent of people who have chemotherapy might need what’s called GRANIX shots.
The white blood cell count gets so low with chemotherapy that medications are needed to boost the white blood cell count to continue treatment. I, unfortunately, fall under that category so not only do I have my chemotherapy, but I have to have those shots to even have chemotherapy because my white blood cells get too low.
I’m very actively looking to find and get second opinions from hospitals that are willing to touch me and get some of this out because I know it would help me in the long run.
Looking for Other Opinions
As of now, they’re telling me that they don’t want to do surgery because of how incredibly advanced my cancer is. They’re saying that it might not be worth it.
However, I’ve read and seen from other people with colorectal cancer that they have better survivability with surgery because the more cancer is in your body, the more opportunities it has to spread and be aggressive.
I’m very actively looking to find and get second opinions from hospitals that are willing to touch me and get some of this out because I know it would help me in the long run. I will be traveling to MD Anderson and Memorial Sloan Kettering, hoping that they can do surgery on me, which will help extend my life. Even though I know it’s risky, I’m willing to do it because the alternative is being on chemo forever.
Getting Help & Support as a Cancer Patient
Having the support of family and friends has been such a huge help and I give so much thanks to the incredible people in my life who have helped me through this.
Some things have personally made it a little bit easier, like trying to buy foods that are pre-cut or pre-chopped. I like getting frozen oatmeal because I can just microwave it.
I’m sicker some days than others and I have found that it helps to have plastic utensils so that I’m not thinking about washing the dishes. To alleviate some of the guilt of buying disposables, I buy the biodegradable kind. You never think about how much something like that would make your life a little bit easier, but it does.
Give yourself grace and find the little things that you deserve to make your life easier.
If I had advocated for myself sooner, my cancer would have been found sooner… Listen to your intuition. You know your body more than anybody else.
Importance of Self-Advocacy
Self-advocacy has been such a big part of my cancer journey because if I had advocated for myself sooner, my cancer would have been found sooner. A lot of people who are as young as me or even younger don’t have a primary care provider.
Maybe they don’t have health insurance and I understand that there is a money barrier to getting treatment for a lot of people. That’s why I’ve been speaking to people who are younger than me and are getting diagnosed with advanced colorectal cancer because of those barriers.
One of the reasons why I started to be so outspoken about my diagnosis is to encourage people to go to the doctor. It’s never normal to have blood in your stool, even if it’s a little bit. Something’s wrong.
Unfortunately, if you’re young, a woman, or a person of color, you have to advocate for yourself so much more than people in different demographics. I hope to inspire people to get the medical help that they need for their symptoms because I was invalidating myself.
I went to my primary care provider and had my physical. I told her all of my digestive issues and bowel symptoms, and she said it was all in my head and that it was anxiety.
Other young people say in the comments on my social media, “This happened to me, too.” That’s one of the reasons why I’m trying to be so outspoken and raise awareness. I want people who have had the same experience to hear my story and say, “I need to take this seriously. Even if a medical professional says that I have nothing to worry about, I need a second opinion. I need to go to a GI specialist.” That is my goal in sharing my story. Don’t let anybody write you off. Get seen. Go to a GI specialist.
All it takes is one who will listen to you and help you. They’re out there. We just have to find them.
Words of Advice
Listen to your intuition. You know your body more than anybody else. A medical professional is diagnosing you based on generalities, but you know yourself better than anybody so if you are having these problems, you deserve to see a specialist and get a second opinion. Don’t listen to the first doctor. Get opinions from a second or a third, especially if your symptoms are persistent.
If your symptoms are persistent and aren’t going away, then something is wrong, especially if you have blood in your stool. That should never be written off. Any kind of blood in your stool is a huge red flag. Pay attention to it.
You deserve to be listened to and taken seriously in a medical setting. If the first doctor isn’t taking you seriously, all it takes is one who will listen to you and help you. They’re out there. We just have to find them.
If you have been invalidated about your bowel health or your symptoms, follow your intuition. As much as we want to completely trust that they have our best interests, that they went to medical school and they’re knowledgeable, that doesn’t mean that they aren’t sometimes wrong and don’t make mistakes or misdiagnoses.
Go out there and fight for yourself. Fight for your health. I hope everybody who hears my story feels very validated to go and seek help.
Learn about success stories, dispel myths about experimental drugs, and understand the broader impact of trial participation on advancing MPN treatments.
Find out about the latest options for myelofibrosis patients, how to deal with myelofibrosis symptoms, and how factors like age, mutation status, treatment history, and personal preferences inform your treatment.
Learn about how the latest advancements may affect your care and get updates on exciting news about the pace and progress of myelofibrosis treatments.
The myelofibrosis panelists discuss momelotinib, fedratinib, selinexor, pelabresib, navitoclax, and other myelofibrosis treatments.
Thank you to GSK and Karyopharm 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. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Stephanie Chuang: I’m the founder of The Patient Story and, more importantly, I also got a blood cancer diagnosis of non-Hodgkin lymphoma a few years ago.
We have so many shared experiences in what we’re looking for and that’s what The Patient Story is all about.
We try to help patients and care partners navigate a cancer diagnosis primarily through in-depth conversations with patients, care partners, and top cancer specialists, like the ones you’ll hear from today.
I want to give special thanks to GSK and Karyopharm for supporting our educational program. Their support helps programs like this more available and free for our audience. But we do want to note The Patient Story retains full editorial control of this entire program. A quick reminder that this is not meant to be a substitute for medical advice.
Our patient moderator is Ruth Fein Revell. Ruth, can you share a little bit more about your story and how you became such a passionate advocate in this space?
Ruth Fein Revell, MPN Patient Advocate
Ruth Fein Revell: Welcome, and thank you for joining us. I’m Ruth Fein, a health and science writer. I’m also a patient and a patient advocate who’s been living with a myeloproliferative neoplasm of one type or another for almost 30 years.
I was diagnosed with essential thrombocythemia when I was 38 years old and raising two young boys. I had had symptoms for many years, but they were disregarded or misdiagnosed. The most troublesome of which was severe, debilitating headaches with blind spots where I literally couldn’t work for hours at a time. I also had bone pain that I experienced for years.
What started as essential thrombocythemia transitioned to polycythemia vera and then progressed to myelofibrosis, which is where I am now. I’m very fortunate to be on a clinical trial that’s working so well that my life is wonderful. I also recognize that everyone isn’t in the same position as I am as there are a lot of people who suffer greatly from myelofibrosis.
I’m speaking with two world-renowned experts in MPNs, Dr. Raajit Rampal of Memorial Sloan Kettering Cancer Center and Dr. Gabriela Hobbs of Dana-Farber/Harvard Cancer Center. Both of you are very, very involved in the patient community and giving back through your knowledge and also taking time to do interviews like this so thank you for that.
We’ll dig into what’s been reported recently at ASH, the annual meeting of the American Society of Hematology where a lot of reports come out. Some of them are quite exciting.
Raajit K. Rampal, MD, PhD
Ruth: Dr. Rampal, give us a little bit of your background, why and how you became interested in MPNs, as well as what your practice looks at.
Dr. Raajit Rampal: I’m a physician-scientist and I lead the MPN program at MSK.
My interest came from the biology side. I’ve been working with Ross Levine for a number of years on the lab side. It became clinically interesting based on what I was learning in the lab so I’ve taken on clinical practice and doing clinical trials for patients in MPN.
This is a field with such an unmet need for effective therapies. Wanting to be at the forefront of that and trying to deliver change where it’s needed have always driven what I want to do. This was the perfect intersection of my scientific and clinical interests.
Gabriela S. Hobbs, MD
Ruth: Dr. Hobbs, would you tell us a little bit about yourself and how your interest in MPNs began?
Dr. Gabriela Hobbs: I am the clinical director of the leukemia service as well as the MPN program at Massachusetts General Hospital in Boston. I’ve always been interested in hematology as far as I can remember, and I was very fortunate to do fellowship training with Dr. Rampal.
For me, myeloproliferative neoplasms in particular are such a rewarding group of patients to take care of. It merges everything that I love about being a physician. I can have very longitudinal as well as very intimate patient relationships with the patients whom I take care of. From the clinical perspective, I found taking care of patients incredibly rewarding and also very varied.
From the scientific perspective, when I was an undergraduate student, we started seeing some of these oral-targeted agents being approved and I knew that was something I wanted to be involved in for my career.
Being a clinical investigator who’s able to see clinicians like Raajit Rampal doing investigations in the lab, finding new targets and new drugs, and being the person who helps take that to clinical trials to the patients is incredibly rewarding.
The most common symptom of patients with myelofibrosis is fatigue, which is probably one of the reasons why myelofibrosis and the other MPNs sometimes take a while to get diagnosed.
Dr. Gabriela Hobbs
Symptoms of Myelofibrosis
Ruth: Myelofibrosis is rare. Some practitioners don’t see very many MF patients. Some patients who are diagnosed with myelofibrosis don’t have enough information or are misguided at times. What do you each see as the major symptoms of myelofibrosis?
Dr. Hobbs: Myelofibrosis is a disease that can present in many different ways. I certainly see completely asymptomatic patients. Their doctor noticed that they had some abnormalities in their blood counts or maybe the patient themself noted that their abdomen felt a little bit different. Patients are on the spectrum of either not having a lot of symptoms or having lots and lots of symptoms.
I would say the most common symptom of patients with myelofibrosis is fatigue, which is probably one of the reasons why myelofibrosis and the other MPNs sometimes take a while to get diagnosed. Other symptoms that we see a lot of are itching, night sweats, fevers, and unintentional weight loss.
Dr. Rampal: Part of the challenge is whether those symptoms are communicated in visits with physicians. Part of that involves us asking the right questions or, at least, training our colleagues to ask the right questions because not everybody is forthcoming about their symptoms. The alternative is that they get so used to their symptoms that it’s the new normal for them and that is sometimes the tougher part of trying to understand how somebody is doing.
Dr. Hobbs: Occasionally, there may be some patients who feel like there are certain symptoms that they wouldn’t bring up to an oncologist. When I meet a patient for the first time and go down my checklist of MPN symptoms, I’ll ask them about itching and they’d say, “How did you know?” We’re fortunate in the MPN world to have these forms that have been validated to help us ask about symptoms that we know are very common in patients with MPN so that we don’t miss anything.
There’s a whole spectrum of symptoms patients can experience.
Dr. Raajit Rampal
Dr. Rampal: Myelofibrosis is a disease of the bone marrow where you have mutated cells that start to grow and take over the bone marrow. They cause inflammation and we think the inflammation causes scarring in the bone marrow. As that happens, the bone marrow starts to contract and is unable to make blood cells. Blood cells start to go into the liver and the spleen to try to produce blood so those organs get larger and cause symptoms.
The inflammation that causes the scarring and damage in the bone marrow also causes people to have symptoms. Those include getting fatigued, losing weight unexpectedly, and having bone pain and aches. There’s a whole spectrum of symptoms patients can experience, but those are among the most common.
That’s how we think about myelofibrosis and how we think about the disease getting worse. We look at blood counts. If people’s blood counts are getting worse, that’s a sign of disease progression. If their spleens or livers are getting larger or they’re feeling worse, all of those are signs of the disease progressing.
There were two phase 3 studies presented about myelofibrosis, the navitoclax and pelabresib studies.
Dr. Gabriela Hobbs
ASH 2023 Updates on Myelofibrosis Treatments
Ruth: We all know there’s been such an explosion in advances in myelofibrosis in recent years. Dr. Hobbs, what came out of ASH 2023 that you’re most excited about?
Dr. Hobbs: It’s exciting. I can’t remember participating in an ASH conference where there were two phase 3 studies presented about myelofibrosis, the navitoclax and pelabresib studies. That in and of itself was a reflection of how far the field has come. We’re now presenting phase 3 studies on drugs that may get approved.
Dr. Rampal: I totally agree. When have we had two phase 3 studies read out? I can’t remember if that’s ever even been the case simultaneously. Thinking about this in the context of our patient audience, this is a clear sign of progress in the field.
Let’s separate that idea from what happens from a regulatory standpoint. You have to get to this point. This is where the finish line is. It is incredibly encouraging that we’ve got drugs to this point of phase 3 where we may have definitive results that could lead to approvals.
What we can probably say, at least with both drugs, is that they have activity in the disease. There’s no question. What happens from here, of course, is up to the FDA. But I’m encouraged by this. I think these drugs have the potential to make a difference for patients so this is exciting.
The combination (ruxolitinib and navitoclax) led to a very dramatic improvement in spleen volume reduction in patients compared to patients who were treated with ruxolitinib alone.
Dr. Gabriela Hobbs
Dr. Hobbs: Both of these studies were phase 3 studies, as Dr. Rampal mentioned. The navitoclax study was the TRANSFORM study that compared ruxolitinib alone to ruxolitinib and navitoclax. They wanted to see if the combination of the two drugs was more effective at improving spleen volume response as well as improving the symptoms of myelofibrosis patients.
They found that the combination led to a very dramatic improvement in spleen volume reduction in patients compared to patients who were treated with ruxolitinib alone. The symptom endpoint was more difficult, as it seemed like symptom improvement was similar with the combination of navitoclax and ruxolitinib compared to ruxolitinib alone.
My take on that is it’s not entirely surprising that a drug like navitoclax would not improve the symptoms, but it certainly didn’t make patients feel worse. I think that’s important when you think about combination therapy as well. I wouldn’t consider that an entirely negative endpoint.
Why should patients care about how big the spleen is and how much it shrinks? That is one of the few things we know that correlates with survival.
Dr. Raajit Rampal
Dr. Rampal: Let me build off of something that Dr. Hobbs said. Symptoms are important to patients and that has to be part of any of our treatment arsenals. But as you said, we want to get drugs that alter the trajectory of the disease and not simply focus on symptom reduction. That has to be part of the conversation going forward as we think about new drugs in this space.
How much weight do we put on symptom reduction as something that we, as a community or the FDA, should fixate on? As long as the drug is not making people feel worse, if it’s doing other things for patients, then maybe that’s where the win is if you will.
About pelabresib, this is a study of the combination of pelabresib, which is a BET inhibitor, plus ruxolitinib versus ruxolitinib alone. The study looked at whether patients had a greater degree of spleen shrinkage with the combination or ruxolitinib alone.
The answer was unequivocally yes. Patients who got the combination had a much greater spleen response, 65% versus 30%.
Why is that important? Why should patients care about how big the spleen is and how much it shrinks? That is one of the few things we know that correlates with survival. We’ve known from the time of ruxolitinib. Spleen shrinkage correlates with overall survival, which is something we all care about deeply.
There was a trend toward the symptoms getting better with the combination. It wasn’t quite statistically significant, but it was certainly a trend that favored the combination.
Importantly, it didn’t add toxicity. We didn’t see that there were any new major signs of toxicity with the two drugs versus one. In oncology, we worry about that all the time. If you add another drug, you may add toxicity, but that wasn’t the case here. From that standpoint, I’m very encouraged by both data sets.
A big takeaway from having all these drugs is that we shouldn’t wait for people to get that sick. We should treat earlier on.
Dr. Raajit Rampal
Treatment Sequencing
Ruth: Dr. Rampal, as we talk about more options available both today and in the future, one of the things that comes up often, especially for higher-risk MF, is sequencing. What are we learning about optimizing the new drugs and combination drug therapies, including determining when and how to switch therapies?
Dr. Rampal: The answer is we don’t know. The broader context of this is that we have more options so that has two implications.
Historically, there’s been a reluctance to start therapy because you didn’t have anything else. If you were in a world where there was only ruxolitinib and it stopped working, what were you going to do? That’s not true anymore.
A big takeaway from having all these drugs is that we shouldn’t wait for people to get that sick. We should treat earlier on. What is earlier on? There’s some ambiguity there, but I think that is one of the implications of having a lot more drugs.
The reality is we’re going to learn how to use these drugs as we go along. There isn’t a great deal of data. We have data on switching from ruxolitinib to fedratinib. We know what happens and how people do when you do that, but do we have data for the other drugs?
If we start going from momelotinib to ruxolitinib, we don’t have the granular data for that. Those are things we’re going to figure out in practice, probably over the next 1 to 2 years, I’d say.
Now that we have four approved JAK inhibitors, there’s no reason to feel like somebody needs to wait for symptoms from their spleen or their disease.
Dr. Gabriela Hobbs
Dr. Hobbs: The point that Dr. Rampal made is so important, especially when we think about what he said about one of the things that we know in myelofibrosis, which is a smaller spleen equals better outcomes.
An important message for patients is exactly what Dr. Rampal said. Now that we have four approved JAK inhibitors, there’s no reason to feel like somebody needs to wait for symptoms from their spleen or their disease because we do have a lot of options.
Now that we have a lot of options, it became a situation where all of us are calling each other and asking, “How do you switch from this one to the other? Have you had a good experience?”
Sometimes, the clinical trials don’t necessarily translate to what we do in clinical practice. Many clinical trials require that patients be completely off of a JAK inhibitor before they switch to the other, which is something that, in practice, probably neither of us would ever really feel like doing. Over the next year, it’s something that we’re going to have some publications about to help guide the broader community to do that safely.
What these data have shown with the FREEDOM trials is that you can better manage gastrointestinal toxicity and that it does get better over time.
Dr. Raajit Rampal
ASH 2023 Updates on Fedratinib
Ruth: Dr. Rampal, what did we learn about fedratinib at ASH 2023?
Dr. Rampal: The most updated data was the FREEDOM2 study, which looked at fedratinib in patients who have been on ruxolitinib. There were earlier trials that looked at the same question, like the JAKARTA2 trial.
When fedratinib was being studied early on, it was seen that there was a lot of gastrointestinal toxicity, like nausea, vomiting, and diarrhea, which was experienced by the majority of patients.
There have been two subsequent trials with fedratinib, the FREEDOM trials, where they aggressively tried to manage the symptoms from the get-go. They didn’t wait for people to get sick or have nausea or diarrhea. When they prescribe the drug, they say, “When you start the drug, if you start to feel nausea, you’re going to take this medication or if any diarrhea starts, you’re going to take this medication.” You don’t let these symptoms get out of control.
What these data have shown with the FREEDOM trials is that you can better manage gastrointestinal toxicity and that it does get better over time. Is that still a side effect that we have to be concerned about? Yes, but it is something that we can manage in most cases if we’re aggressive about doing that upfront and the expectation is that it will get better over time.
The data (on selinexor) is still in earlier stages so I’m waiting to see if this agent is well-tolerated by patients.
Dr. Gabriela Hobbs
ASH 2023 Updates on Selinexor
Ruth: Dr. Hobbs, what about selinexor?
Dr. Hobbs: Selinexor has been interesting as well. This is a newer agent that we’ve started to see some preliminary results on and they presented their data also in combination with ruxolitinib. This agent seems to have very impressive responses in terms of shrinking the spleen and improving symptoms as well.
The data is still in earlier stages so I’m waiting to see if this agent is well-tolerated by patients. We’ll have to see how the later studies will pan out, but it’s still exciting.
Having this fourth agent will be very helpful in the management of patients with MF, especially patients who have anemia and aren’t able to get a bone marrow transplant.
Dr. Gabriela Hobbs
ASH 2023 Updates on Momelotinib
Ruth: There’s an unmet need for the treatment of anemia for patients with MPN, specifically myelofibrosis, which brings us to momelotinib and a few others.
Dr. Hobbs: We’ve mentioned that there are now four JAK inhibitors that are approved for the treatment of myelofibrosis. We have pacritinib, ruxolitinib, fedratinib, and momelotinib, which was approved at the end of September 2023.
Momelotinib is a JAK inhibitor that was approved a little bit differently than the others. Its main indication is for patients who have myelofibrosis and anemia. Anemia has been an unmet need in the management of myelofibrosis so it’s exciting to have a drug like momelotinib that can help anemia and also a drug like pacritinib that can also help anemia in a subset of patients.
In my practice, I’ve noticed that since the approval of this agent, there have been many patients, especially those who are active online, in their communities, and in patient advocacy organizations, who have been excited or eager to switch to this medication.
I do think that having this fourth agent will be very helpful in the management of patients with MF, especially patients who have anemia and aren’t able to get a bone marrow transplant.
When we have patients with myelofibrosis who have anemia, it’s important to consider if a bone marrow transplant is the right therapy. But for those who can’t receive that therapy, momelotinib takes care of a lot of the parts of the disease that we worry about, like the symptoms, the spleen, and the low red blood cell numbers.
In some cases, they take patients who are relying on transfusions and convert them to not needing a transfusion, which is important in terms of survival.
Dr. Raajit Rampal
Dr. Rampal: There is so much going on in anemia in this disease, it’s remarkable. It’s a problem for which we had no good solutions until very recently.
As you mentioned, momelotinib and pacritinib also seem to have an effect in a proportion of patients where they can increase the hemoglobin. In some cases, they take patients who are relying on transfusions and convert them to not needing a transfusion, which is important in terms of survival.
We know that that correlates with survival, but it’s also quality of life. If you have a patient who’s getting stuck in the transfusion chair for 4 to 6 hours a week or more and that is no longer an issue, that is immensely important to their quality of life. It’s an important problem.
There are some other drugs in development and that includes a drug called luspatercept, which is FDA-approved for myelodysplastic syndrome. There are also some other drugs from a few other companies that are anemia-specific and there was some data presented at ASH on them. There are early signs of efficacy. Too early to say anything definitively, but at least it looks like these are drugs that will be studied further.
What’s been practice-changing is having the approval of the last JAK inhibitor, which is momelotinib.
Dr. Gabriela Hobbs
Practice-Changing Updates
Ruth: We talked about what’s happened in the lab, what’s in the drug approval process, what’s recently been approved, and where our needs still are. What came out of ASH that you think is truly practice-changing immediately or in the near future?
Dr. Hobbs: What was very exciting was seeing the two phase 3 studies. Although those two drugs, pelabresib and navitoclax, are still not approved, they are potentially closer to our doorstep and something that we will have to have conversations about how to use.
Do we use them in combination with the JAK inhibitor that they were studied with? Do we use them with other JAK inhibitors? How do we think about sequencing when we’re talking about combination? Although neither of these agents is approved, these are questions that need to be discussed.
What’s been practice-changing is having the approval of the last JAK inhibitor, which is momelotinib. We now have four drugs that we can prescribe to our patients when we see them in the clinic, especially those who have anemia.
There are so many drugs coming down the pipeline and showing interesting activity, especially some of those showing activity by themselves.
Dr. Gabriela Hobbs
Personalizing Myelofibrosis Treatment
Ruth: The drugs and the studies we’ve talked about are all very exciting, but what other treatments are you excited to share with patients to help you personalize treatment?
Dr. Hobbs: We’ve discussed the MANIFEST and TRANSFORM studies looking at combination studies in phase 3. There are so many drugs that are being evaluated and it’s been very exciting to be at an ASH where we hear about so many different mechanisms of action being explored. Many of those are by themselves and some of them are now getting to the point where they’re used in combination.
To mention a few, there was a compound called a PIM1 kinase inhibitor, another one that inhibits lysyl oxidase, which is a group of enzymes that have to do with making fibrosis or scarring happen in the bone marrow, and an LSD1 inhibitor called bomedemstat.
There are so many drugs coming down the pipeline and showing interesting activity, especially some of those showing activity by themselves. Generally speaking, when we have new drugs that are not JAK inhibitors used by themselves, we rarely see a lot of clinical activity so I thought that that was exciting.
Individualized medicine is the holy grail and there’s a lot of different ways to think about it. There’s how we use the drugs we have now and what some of the newer drugs may be able to do for us.
Dr. Raajit Rampal
Dr. Rampal: There is this whole pipeline of things coming forward, which is amazing for this field. We spent some time talking about the top-line phase 3. But as Dr. Hobbs mentioned, there are all of these drugs that are in early development that are showing us that they may be able to do something. Even beyond what we have, some things are part of the big picture here.
Individualized medicine is the holy grail and there’s a lot of different ways to think about it. There’s how we use the drugs we have now and what some of the newer drugs may be able to do for us.
A key example of this is calreticulin. There’s been a focus on this. There are drugs in investigation that are specific antibodies that target calreticulin. That could be a game-changer if those things work. Pre-clinically, there’s good rationale. Imagine a future where if those drugs are effective, then for calreticulin-mutant patients, this is what we use. We have a drug that targets your mutation. That is where we want to be.
Of course, other mutations occur in the disease and we’ve already started trying to do personalized medicine for patients. Some patients have an IDH mutation that occurs typically in people with more advanced diseases.
We’ve completed a trial where we used a JAK inhibitor plus an IDH inhibitor. IDH inhibitors are FDA-approved for people with leukemia and we’ve combined those drugs and seen very good results. That’s an example of genetically-informed personalized medicine, but there’s also how you use the drugs we have in practice.
Dr. Hobbs: We’ve mentioned a few times that we have four different JAK inhibitors and it’s important to know which patients those are going to help. Are there certain situations where we should use one JAK inhibitor versus another?
At ASH 2023, we saw an update on a similar study that was published recently by the folks who looked at pacritinib. They found that patients who have a symptom improvement of greater than 10% had an improvement in survival, which is similar to what they showed recently with patients on pacritinib having a survival benefit if they also had a spleen volume reduction.
Again, that goes to the theme that we were saying. It’s important to use these drugs and make sure that those drugs are doing what they’re supposed to be doing for the patient. We have endpoints that help patients not only to live better but hopefully to live longer. That can also help the practicing doctor to say this drug is not meeting those endpoints. It’s not helping my patient have an improvement in their spleen or their symptoms. We have other drugs that we should we should think about switching to.
One of the areas where there’s a lot of interest is looking at pre-fibrotic myelofibrosis or early myelofibrosis to see if we can get to the disease earlier before a lot of scarring develops.
Dr. Gabriela Hobbs
ASH 2023 Updates on Interferon
Ruth: There was an interesting study presented at ASH about interferon-α versus hydroxyurea, which is the oldest of the drugs still used for myelofibrosis or MPNs. This study was in untreated MPN patients who were unable to take ruxolitinib. What did we learn?
Dr. Hobbs: Several abstracts were presented with interferon. One was the updated results of the DALIAH study comparing pegylated interferon to hydroxyurea for patients with earlier disease essential thrombocythemia and polycythemia vera. There was also another study looking at earlier myelofibrosis, like pre-fibrotic myelofibrosis.
There’s been a lot of interest in looking at interferons in general across the spectrum of the disease. One of the areas where there’s a lot of interest is looking at pre-fibrotic myelofibrosis or early myelofibrosis to see if we can get to the disease earlier before a lot of scarring develops.
If we look at all the characteristics of the patients who had stable disease for years versus those who progressed, is there a difference that AI can say if you look at these particular parameters, this is a warning sign?
Dr. Raajit Rampal
Artificial Intelligence in Hematology
Ruth: There was a fascinating presentation on the use of artificial intelligence, specifically to differentiate between essential thrombocythemia and pre-fibrotic primary myelofibrosis. Is that something that you see coming into practice or are we way off on that?
Dr. Rampal: We’ll level set by talking about what we mean by AI, which neither of us are experts in. One of the powers of AI is to take broad sets of data and identify patterns. That is a very simplistic way of thinking about the many things that AI can do and is built to do. It can take thousands of variables and find patterns that humans aren’t going to be able to find in real time.
This is an example of what you’re talking about. If you took thousands of bone marrow samples and you said that clinically, these people look like ET, but based on the other parameters that we have, these people look like myelofibrosis. Is AI going to be able to better discriminate versus a human and say this pattern better fits the ET pattern and that pattern better fits the MF pattern?
It will help us refine some of the key characteristics of the disease. The hope is that it may also give us some clues for things like progression if you look at the pattern of a lot of patients. We’re talking about thousands of patients and if we look at all the characteristics of the patients who had stable disease for years versus those who progressed, is there a difference that AI can say if you look at these particular parameters, this is a warning sign? That I think is part of where we think this is going to go.
There are lots of great resources online where, as a patient, you can advocate for yourself to recommend different treatments to your provider to make sure that you’re getting the most updated care.
Dr. Gabriela Hobbs
How Patients Can Be More Proactive in Their Treatment
Ruth: Now that we’ve heard updates out of ASH 2023, what can a patient bring to their community hematology-oncologist as opposed to waiting for it to trickle down? What are some of the ways that a patient can be more proactive with knowing what we now know?
Dr. Hobbs: If you’re a patient or a family member of a patient, you’re already taking those steps that are so important. It’s important to remember that myeloproliferative neoplasms are rare diseases so not everybody has access to subspecialized care.
What’s incredible about the MPN community is that the group of clinicians who treat MPN and are doing research in MPN are extremely committed and passionate about treating these diseases. We’re excited to work with industry partners who are similarly very passionate about finding new therapies for these diseases.
There are lots of great resources online where, as a patient, you can advocate for yourself to recommend different treatments to your provider to make sure that you’re getting the most updated care.
It’s worth asking your physician: when is it time for me to get started on treatment? If you are at the point of needing treatment, it may be worth getting a consultation in a center where there’s a lot of experience.
Dr. Raajit Rampal
Dr. Rampal: If you’re a patient who’s being cared for in the community, it’s worth asking your physician: when is it time for me to get started on treatment? This is an evolving space. We’re more and more convinced that earlier may be more beneficial, but there is a danger in waiting too long.
If you are at the point of needing treatment, it may be worth getting a consultation in a center where there’s a lot of experience. We, who are focused on this, have the forefront of the developments at our fingertips. Doctors in the community setting are busy seeing a lot of different types of cancers. They have to keep up on all of this and they may not have immediate access to that information.
If it is time to get treated, it may be worth a consultation at least to say, “Is this the right thing? Or is there a compelling clinical trial that maybe may make more sense right in the current era?”
We’re bringing back hope. We’ve seen more developments at ASH 2023 than in maybe any prior in the last ten years that I can think of. That’s not unimportant.
Ruth: That’s a very hopeful message. We seem to say that every year but maybe now even more than ever.
Conclusion
Ruth: From a patient perspective, one of the themes that came out of ASH 2023 is all these new approaches to old diseases. It’s not that we’ve discovered new diseases. It’s that these are diseases and patients who have not had solutions for so long or our options have been so limited and now there are more and more options.
Thank you both so much for your time, Dr. Hobbs and Dr. Rampal. Always my pleasure.
Stephanie: Thank you so much, Ruth, for being our incredible patient advocate and moderator. Also to Drs. Hobbs and Rampal for the work and research you do to help move the landscape of myelofibrosis options.
We hope that you walk away with a better understanding of the latest treatments and clinical trials in myelofibrosis. They may or may not be right for you, but it is our goal to make sure you feel empowered to make a decision for yourself.
Thank you and we hope to see you again at a future program at The Patient Story.
Special thanks again to GSK and Karyopharm for their support of our independent patient education content. The Patient Story retains full editorial control.
Brandie shares her journey with stage 4 leiomyosarcoma. She had a history of painful menstrual periods and a family history of fibroids and endometriosis, but in the summer of 2021, Brandie experienced worsening symptoms, including severe urinary urgency. Assuming it was related to fibroids, she underwent ovary removal surgery and an elective hysterectomy.
Unexpectedly, the pathology report revealed leiomyosarcoma, a rare cancer of the smooth muscle. Further surgeries were performed to remove metastatic implants. She also underwent chemotherapy regimens, which proved ineffective.
Seeking a second opinion at MD Anderson, she was recommended radiation. Despite its damaging effects on her bladder and colon, Brandie remained hopeful. However, the tumor continued to grow, leading to a failed surgery attempt. Desperate for options, she sought opinions from other specialists and found a sarcoma surgeon at City of Hope.
In April 2023, Brandie underwent a 14-hour surgery. The tumor was successfully removed, but her medical oncologist warned about the risk of microscopic cells in her bloodstream. A follow-up scan in September revealed a lung nodule, leading to a pulmonary wedge resection in October.
Throughout her leiomyosarcoma treatment, Brandie faced significant side effects, including neuropathy, muscle loss, and urinary incontinence. She maintained a positive outlook and her most recent scans in January 2024 showed no evidence of disease.
Despite the challenges, Brandie emphasizes the importance of seeing a specialist, getting multiple opinions, and continuing support for cancer survivors. She also shares her experience with having an ostomy, expressing gratitude for the improved quality of life it brought. Brandie encourages others to openly discuss their cancer journey and seek help when needed.
In addition to Brandie’s narrative, The Patient Story offers a diverse collection of sarcoma stories. These empowering stories provide real-life experiences, valuable insights, and perspectives on symptoms, diagnosis, and treatment options for cancer.
I have a bit of a medical background so I’m running the different possible scenarios through my head. It never crossed my mind that it could be cancer.
Introduction
I live in Northern California. I’m a registered nurse and work as an educator for a medical device company.
I love to travel. Before my diagnosis, I was into fitness. I did CrossFit and was a Peloton enthusiast.
I have a 6-year-old big, fat orange tabby cat named Toby and a wonderful boyfriend named Brad, who is a high school math teacher.
Pre-diagnosis
Initial Symptoms
I’ve always had painful menstrual periods since I was a teenager and a family history of fibroids and endometriosis. I always suspected that there was something unusual going on.
Doctors weren’t concerned over the years. There wasn’t ever any evidence of anything wrong. They told me, “You probably do have endometriosis, but we have to do surgery to confirm that so we’re just going to assume you do. If it gets to the point where you need to have surgery, then we can confirm it that way.”
Symptoms Worsen
Fast forward to the summer of 2021, I started having heavier, more painful menstrual periods, which was unusual. I also had a sensation of fullness or bloating in my pelvis. What spurred me to see a doctor emergently was having severe urinary urgency.
I have a bit of a medical background so I’m running the different possible scenarios through my head. It never crossed my mind that it could be cancer. I assumed I had a fibroid. I’d been told years ago that I had a teeny tiny one so I assumed that it was related to that.
Oophorectomy (Ovary Removal Surgery)
I ended up getting rushed into surgery. At this point, cancer’s still not on my radar. I had a large cyst on my ovary, which was funny that it didn’t raise alarm bells for me. It didn’t even occur to me that it could be malignant. They ended up having to remove my ovary because the cyst was solid.
Everything came back benign. But the doctor said, “What do you want to do about this large fibroid in your uterus?” I had turned 38 at the time and wasn’t interested in having children so I told the doctor, “Let’s do a hysterectomy. I know fibroids can come back. I want to do a one-and-done.”
The surgeon gets on the call and tells me, ‘I’m sorry, but your pathology report came back and it was not a fibroid. It was a sarcoma.’
Elective Hysterectomy
I had an elective hysterectomy and a couple of weeks later, I got a phone call from the clinic and they said, “Do you have time this afternoon for a video visit with your surgeon?” I knew something was up.
Diagnosis
Getting the Diagnosis of Stage 4 Leiomyosarcoma
The surgeon gets on the call and tells me, “I’m sorry, but your pathology report came back and it was not a fibroid. It was a sarcoma.” He kept saying, “Wow,” and added, “I haven’t seen this in decades.” He told me that he would be referring me to an oncologist and that’s where it all began.
We were hopeful that this sarcoma was confined to my uterus and since my uterus was gone, maybe this was it. Maybe this was my whole cancer story.
Secondary Oophorectomy
A couple of months later, the oncologist decided that she wanted to remove my remaining ovary because the tumor had estrogen receptors. When she went in, she found metastatic implants throughout my pelvis, which were confirmed to be sarcoma.
There were about six tiny nodules throughout my pelvis. They were attached to my peritoneum, bowel, and diaphragm, and they removed them all.
There was one small piece on my colon that they left behind. The surgeon, who was a gynecologic oncologist, told me that she was concerned about damaging my colon so she didn’t want to mess with it.
When I woke up from surgery, the fellow talked to me and said, “I’m so sorry.” I was still hazy coming out of anesthesia. She put her hand on my arm and said, “I’m so sorry, nobody deserves this.” I said, “What are you talking about?” I still was not fully with what was going on and she said, “We found more cancer in your pelvis so we’re going to have you start chemo in three weeks.”
At that point, I thought, “All right, we got this. I’m going to do chemo and it’s going to be what it is.” It turns out, I have leiomyosarcoma, a cancer of the smooth muscle, and it’s pretty much resistant to treatment.
I did 12 infusions, but the tumor doubled in size.
Treatment for Stage 4 Leiomyosarcoma
Chemotherapy (Gemcitabine & Docetaxel)
I did about six rounds of gemcitabine and docetaxel for four months, which I had an allergic reaction to. I did 12 infusions, but the tumor doubled in size so it did nothing.
Chemotherapy (Doxorubicin & Ifosfamide)
They decided to start me on a more aggressive chemotherapy that required me to be hospitalized for five days every three weeks. I started doxorubicin, or what they call the Red Devil, and ifosfamide, which can cause damage to your bladder, which is part of the reason why I had to be hospitalized and monitored closely while undergoing chemotherapy.
I did three rounds of that in about nine weeks and stayed 15 days or so in the hospital for those chemo infusions. They sent me for a scan and it doubled in size again so the tumor was not having it.
Tumor Not Responding to Chemo
They started weighing the different options. “It’s starting to invade your bladder and your sigmoid colon. We need to see if we can go in and remove this. If this looks like a surgery that’s not going to cause a ton of damage to your insides, we want to get it done and get you back on another chemo.”
The MRI showed that there’s too much invasion into my internal organs that if they do a surgery, it’s not going to be straightforward. It’s going to be a long recovery. It’s going to delay getting on to another systemic therapy so they decided that they didn’t want to operate.
I was pretty freaked out. Two chemo regimens had already failed me and they wanted to put me on a third. I’m thinking, What are the chances of that doing anything at this point?
Sometimes I wonder if things would have played out differently if I had been with a sarcoma specialist from the beginning.
Getting a Second Opinion
I got on a plane and went to MD Anderson to see a team of specialists who only treated sarcoma. I guess that was my first mistake as the doctor I had been seeing was not a sarcoma specialist. Sometimes I wonder if things would have played out differently if I had been with a sarcoma specialist from the beginning.
The team at MD Anderson said, “We’re going to get some more scans. We’re going to bring this to the tumor board then we’re going to call you and let you know what we think we should do next.”
A few days later, they called me and said they thought radiation was the best way to go. I temporarily relocated to Houston for about six weeks. Luckily, I have an amazing friend who let me stay with her and her husband. It was nice and comfortable. I had my own room. It was a good experience despite the reason why I was there.
Radiation
I went through 25 fractions of radiation. I went every single day. It was the first time that anybody had given me any hope. She told me, “I’ve seen your type of tumor respond to radiation before.” She explained how they dosed it in a way that it was going to cover a margin around the tumor that would reduce the risk of it recurring by 50%. I was on cloud nine, thinking I finally figured out something that was going to work.
But even as a nurse, I didn’t realize how devastating radiation can be to your body. I tolerated it pretty well while I was going through it, but it damaged my bladder severely and my colon. I start having bowel issues and urinary incontinence. I thought, This is a means to an end.
I finished radiation the day before Thanksgiving 2022. I packed all my things, went back home, and spent the holidays with my family. That was the order from my doctors. “Go home, spend the holidays with your family, rest, recover from radiation, and we’re going to see you back at the beginning of January for your surgery. We’re going to remove this tumor.”
I thought, If these surgeons at this top hospital are not comfortable operating on me, then I’m a goner. This is it.
Tumor Grew
They scheduled me for surgery. I went out a few days early and my mom flew out with me. They did scans and a bunch of tests. I showed up on the morning of my pre-op, the day before the surgery was supposed to take place, and the surgeon told me, “I’m sorry. It looks like your tumor has grown and I can’t operate on you.”
That was probably the lowest point for me right there. I felt pretty hopeless. I went through all of this to get this thing out of me. It was 12 cm. It was huge and uncomfortable. It was crushing my bladder. I was having bowel issues. I was getting obstructed and I was miserable. I thought, If these surgeons at this top hospital are not comfortable operating on me, then I’m a goner. This is it.
Follow-up Appointment with Oncologist
They decided that they were going to have me follow up with my medical oncologist before I flew back home to California. I moped around for a couple of days then I got in to see him.
He said, “You know what? It might still be inflamed from the radiation. It’s negligibly larger. I’m going to run this by the tumor board, but we’re going to send you home for six more weeks. We’re going to scan you again and then make a decision. If it is larger, we’re going to consider systemic therapy again. But if it’s not, then we’ll talk about what we can do.”
I had this sense of relief. I’m going to go back to living my life for six more weeks.
The team at City of Hope brought my case to the tumor board and found out that there was a surgeon there who did nothing but operate on soft tissue sarcoma.
Getting Additional Opinions
During those six weeks, I got more opinions. I saw a doctor at Memorial Sloan-Kettering and a doctor at City of Hope. The team at City of Hope brought my case to the tumor board and found out that there was a surgeon there who did nothing but operate on soft tissue sarcoma.
I felt like it was all serendipitous. When I was first diagnosed, I looked for other sarcoma patients and their stories on social media to help guide me through what I was going through. I came across a surgeon whose Instagram name was @sarcomasurgeon. He turned out to be the surgeon who said that he would be able to help me. I thought, Everything’s aligning. This is meant to be. This guy’s going to save my life.
Surgery to Remove the Tumor
I went for my pre-op and saw the surgeon. I said, “Things are not moving.” He admitted me to the hospital right then and there, and I had surgery the next day.
The surgery was supposed to be on April 20th and it ended up happening earlier on April 12, 2023. I was brought in emergently. I had an almost 14-hour surgery.
There were five different surgeons involved. Dr. Tseng, a sarcoma oncologist at City of Hope, led the team, which included 1 or 2 urologists and a gynecologic surgeon. They had to do a diverting colostomy so there was a colorectal surgeon involved.
They ended up having to call on vascular surgery because the tumor was fused to the neurovascular bundle in the left side of my pelvis so the major artery in my pelvis was severed. They had to graft it and repair it because the tumor was fused to it. The tumor was stuck to my sigmoid colon. It had not grown into my colon, but it was smashing it so severely that nothing could pass through.
They had to remove a piece of my sigmoid colon and half of my bladder. The tumor was attached to my left distal ureter, which is the tube that goes from your kidney to your bladder, so they had to remove part of that.
I didn’t care what morbidities or complications I was left with. I wanted the tumor out and I didn’t care what they had to do.
My ureter wasn’t long enough to reach my bladder anymore so they had to reroute my ureters so that they funneled into one. My insides have been MacGyver-ed. They grafted the arterial damage to the artery in my pelvis.
When I went in for the surgery, there was some discrepancy because the radiologist said they were concerned that the cancer had implanted in my peritoneum so they were calling it sarcomatosis, which would pretty much be there’s nothing we can do at this point.
He told me that he did not see that. He did not agree with that radiologist and that we were going to proceed with the surgery, but I needed to be aware that if he opened me up and saw that, then he would have to abort the surgery. That was a big thing going in because I didn’t know if it was going to be successful. I didn’t know if they would be able to get the tumor out at all.
After a few hours, my mom was under the impression that they must be proceeding with the surgery because I’d been in there that long. That was a little bit nerve-wracking. I didn’t care what morbidities or complications I was left with. I wanted the tumor out and I didn’t care what they had to do.
Recovering from Surgery
I spent two days in the ICU and about 10 days total in the hospital. They wouldn’t let me go home to Northern California for another month because they wanted me to be close by. I stayed with a friend in the LA area who was a nurse and took great care of me. I have been fortunate to have so many good friends through all of this who have been willing to step up and help out.
I had a nephrostomy tube in my back to drain my kidney, a drain in my abdomen, and a catheter in my bladder. I had all these tubes coming out of me and they sent me home that way for about a month before they finally let me go home to Northern California.
I come back for my first scans and there is a nodule in my lung.
He said, ‘We’re not going to mess around. We’re not going to wait and see what this turns into. I’m sending you to a thoracic surgeon and having that piece of your lung removed.’
Status Post-Surgery
After the surgery, the surgeon came to talk to me and said, “We got the whole tumor out with clear margins, but with sarcoma, that doesn’t mean a whole lot. There could be microscopic cells floating throughout your bloodstream that are waiting to re-implant somewhere else. I’m not telling you that to scare you, but that’s the reality and I want you to be aware.”
I followed up a few weeks later with my medical oncologist and he said, “I consider you to be cured.” I was elated at this point. This was June 2023 and I’m being told that I’m cured of stage 4 sarcoma. This made me laugh. I told him, “Okay. I know we’re going to continue with the scans every four months. I’m going to be cautiously optimistic because I understand the risks of this returning,” and he said, “No, no, no, you should be grotesquely optimistic.” There was a big celebration at this point.
Post-Surgery Scan
Fast forward to September, I come back for my first scans and there is a nodule in my lung. My doctor is still very optimistic. He said, “Look, it looks like that nodule has been there for a long time. I went back and looked at your old scans. It decided to grow a little bit and it was still less than a centimeter. It was tiny.”
He said, “We’re not going to mess around. We’re not going to wait and see what this turns into. I’m sending you to a thoracic surgeon and having that piece of your lung removed.”
Pulmonary Wedge Resection
In October, I had a pulmonary wedge resection. They removed the top part of my left lung with the tumor. It was confirmed to be metastatic sarcoma, but they got it all out. Turns out that’s the best-case scenario for me. If something pops up and it is operable, then that’s the plan because we know that I don’t respond to chemo.
When you get diagnosed with cancer, your whole life changes.
Side Effects of Treatment
All of the treatments that I’ve been through have left me with some pretty significant impairments. I have pretty severe neuropathy in both feet and damage to a nerve in my left thigh. I have a lot of muscle loss. I have been able to regain a lot of strength months after surgery, but for a while, I was falling a lot. I even fell and broke my wrist at one point.
I had a lot of instability, like the feeling of not being able to feel your feet. Your feet feel like they’re asleep, like pins and needles 24/7 so that’s pretty uncomfortable. But like I said, I’m alive.
Follow-up Scans
My most recent scans were on January 4, 2024, and they were perfectly clear for the first time since I started this whole journey.
Sharing My Cancer Story
Part of the reason why I like to be so open about what I’ve been going through is sarcoma is a rare cancer and a lot of people don’t know what it is. When they hear the word sarcoma, they don’t necessarily know that it’s cancer or what it affects. It makes up less than 1% of all diagnosed cancers and there are over 80 subtypes. There’s not a lot of research. There aren’t a lot of treatment options.
When you get diagnosed with cancer, your whole life changes. It’s not as simple as, “I’m going to do chemo or have this surgery and then I’m going to go on my merry way and put this behind me.” For most people, that’s not the case.
The very first time my care team said that a colostomy was a possibility, I did everything I could to mentally prepare myself.
Having a Colostomy Bag
The colostomy has not been an issue at all. They told me that it would potentially be reversible. I don’t even care. It’s honestly improved my quality of life. I don’t mind it at all. It’s not hard to manage.
Most people wouldn’t know it was there if I didn’t tell them and the people who do know are people who know what to look for because they’re medical professionals that I encounter in my day-to-day life. Nobody needs to know it’s there if I don’t tell them.
I’ve had a pretty significant injury to my bladder so after all of the radiation and the surgery, I was left with a fistula. A hole that developed in my bladder has left me with pretty severe urinary incontinence, which is difficult for a woman in her late 30s who likes to travel and do things.
I’ve been confined to managing that. I spent about four months with a catheter in my bladder in 2023. We’ve tried a lot of things to get it to heal. I saw a specialist who attempted to repair it but my bladder and vaginal tissue were so severely damaged from all the radiation and the surgery that the repair did not work.
I’m getting ready to have an ileal conduit surgery, which is a urostomy so I’m going to have two ostomies. We decided that this was the quickest way to get my quality of life back so I could get back to traveling, going on girls’ trips, getting in a swimsuit, and not having to worry about urinary incontinence or having a catheter.
The very first time my care team said that a colostomy was a possibility, I did everything I could to mentally prepare myself. I went on Instagram and started following people who have colostomies, watching their day-to-day lives, how they dress, how they manage it, and how they maintain it. It helped me wrap my head around these women living these lives. They’re in swimsuits, wearing cute clothes, doing this and that, and nobody has to know that they have a colostomy. I can do this.
When I went in for the surgery, they still didn’t know if I would need it or not. It was going to be a surprise when I woke up. But when they told me, I wasn’t upset, not even a little bit. I said, “You guys did what you had to do to save my life and this is my new normal.”
For the most part, it doesn’t affect me. It’s not a problem. It’s only improved my quality of life.
When I came out of surgery, there were so many things going on that I didn’t pay any attention to it. The ostomy nurse saw me several times before I was discharged from the hospital and made sure I was comfortable changing it. She taught me how to do it and then she had me do it with her there so that she could watch, critique, and offer suggestions. We talked about the different products that were available and what I should try. She set me up with my first order of supplies and then I went from there.
I do think that I have a little bit of an unfair advantage being a nurse. Things that might be a little weird or gross to a regular person don’t necessarily gross me out, but it hasn’t been trouble. I haven’t had any horror stories, like a leakage accident, happen.
There have been times when the bag starts to detach from my abdomen, but I usually can tell that something’s going awry and I can intervene pretty quickly. For the most part, it doesn’t affect me. It’s not a problem. It’s only improved my quality of life.
Words of Advice
If you were to ever be diagnosed with sarcoma, the very first thing you need to do is search for a sarcoma center at a hospital with a cancer center. Sarcoma does not behave the same way as solid tumor cancers. It’s its own beast and requires somebody who knows exactly how it behaves and how to treat it.
I do wonder what if. What if I had been seeing a sarcoma specialist from the get-go? Not only should you see a sarcoma specialist right off the bat, but you should also get multiple opinions. I know that can seem daunting when you’re faced with a new diagnosis. You feel overwhelmed and don’t know what to do first.
I very much remember being in that situation where somebody like me, who is a nurse, who wants to understand everything about what’s going on, shut down. I wanted to curl up in a fetal position and let somebody else deal with it. It was too much for me to handle.
Once somebody is treated for cancer and receives clear scans or told that they have no evidence of disease, they still need support. It doesn’t end right there.
Fortunately, I have a really good friend who helped her mom navigate through a colon cancer diagnosis and she knew how to be that advocate. She stepped in and made phone calls for me. She handled what I was not capable of handling at the moment. I’m really grateful to her for that.
She set up multiple opinions for me because it’s overwhelming. You just want to go with what the first doctor says, get started with treatment, and get going, but it’s important to get multiple opinions from places that specialize in sarcoma.
Once somebody is treated for cancer and receives clear scans or told that they have no evidence of disease, they still need support. It doesn’t end right there. I’m going to continue to be scanned every four months, probably for the rest of my life, and I have to deal with that paralyzing fear every time.
I have all of these disabilities and complications to deal with now. This is the price that I had to pay to have more time on this earth and I would do it again if I had to.
Continue to support your friends who have been through cancer because it doesn’t go away once they get that all clear.
Honestly, if you’re comfortable, ask your doctor for medications that can help. It’s okay to not be able to deal with it all on your own. I take medication for anxiety when I go in for scans and usually, I have to start taking it a few days before.
This might be different for other people, but I can show up to surgery alone; it doesn’t scare me. I can go sit in a chemo chair alone; that’s fine. But when I’m going to have the doctor deliver my scan results, I need to have somebody close to me with me. I do my best to remind myself that whatever the result is, we will take the next steps and deal with it.
1st Symptoms: Pain behind left knee, needle-like sensation in left foot Treatment: Surgery to remove what was thought to be benign tumor, chemotherapy, final surgery, radiation (36 sessions)
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Cancer Details: <5% of adult sarcomas 1st Symptoms: severe intolerance to food, nausea Treatment: Cholecystectomy, Chemo (Gemcitabine and Taxotere), Whipple surgery
Cancer details: Rare, <3% of all soft tissue tumors, more common in women 1st Symptoms: leg tightness, increased swelling in leg Treatment: Chemo infusion (Methotrexate, Navelbene), oral chemo (Nexovar)
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Cancer details: Rare, <3% of all soft tissue tumors, more common in women 1st Symptoms: lump found in right armpit Treatment: Chemo, radiation, targeted therapy, clinical trials, surgery, including forequarter amputation
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Dr. Matasar discusses some of the most exciting news coming out of ASH 2023.
The American Society of Hematology (ASH) hosts an annual comprehensive meeting that covers new research, scientific abstracts, and the latest topics in hematology.
This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
I’m bringing updates from ASH 2023 about blood cancers to help you better understand this area.
ASH is a major organization in blood cancers. It’s the American Society of Hematology and we have a meeting every December that rotates among different cities. It’s a chance for us to present our latest data, meet colleagues and friends, and talk about future projects and how we’re going to continue to make progress towards curing blood cancers.
There are other medicines that we know are effective in treating Hodgkin lymphoma, including a family of immunotherapies called checkpoint inhibitors.
Dr. Matthew Matasar
What are the updates from ASH 2023 with Hodgkin lymphoma treatments?
There is ongoing progress in our treatment of patients with Hodgkin lymphoma. We have some provocative early data.
For a long time, the standard of care for Hodgkin lymphoma was the chemotherapy regimen called ABVD. That changed a few years back as we learned that using a newer medicine called brentuximab vedotin or ADCETRIS instead of one of the older chemotherapy medicines cured more people.
There are other medicines that we know are effective in treating Hodgkin lymphoma, including a family of immunotherapies called checkpoint inhibitors. We’re now getting some readout about whether we can incorporate those medicines into the first-line treatment of patients with Hodgkin lymphoma, either in early-stage or even advanced-stage disease. Can we cure more patients that way than with our current traditional standards?
The answer begins to look like it could be yes. There’s some very interesting data at ASH, particularly looking at older patients with Hodgkin lymphoma, showing that substituting this checkpoint inhibitor treatment for brentuximab seems to be safer and more effective, and that’s a win-win.
ABVD remains the standard of care, however, for patients with early-stage Hodgkin lymphoma.
Dr. Matthew Matasar
When is bleomycin used in treatment for patients with Hodgkin lymphoma?
Bleomycin is an old standard chemotherapy medicine that’s been around longer than I’ve been doing this. It’s been a standard part of older traditional chemotherapy programs in Hodgkin lymphoma. It’s the B in the ABVD and it was well-known for both its effectiveness but also its potential risks.
Chief among them is a risk of lung injury that can happen unpredictably but can be severe when it occurs. We know that it can happen more commonly in older people, although we don’t know why.
That was the impetus for some of these studies that led to progress. Can we get rid of bleomycin altogether and switch it out for some of these newer medicines? The current program of AAVD, where bleomycin was substituted with Adcetris, an antibody-drug conjugate, showed that we cured more people that way.
ABVD remains the standard of care, however, for patients with early-stage Hodgkin lymphoma because those patients are at lower risk both for lung injury because they get less chemo and for relapsing because our cure rate is so high in early-stage disease.
Nonetheless, we do have evidence at ASH 2023. A study being presented combining Adcetris, a checkpoint inhibitor called nivolumab or nivo for short, and the VD (vinblastine and dacarbazine), showing that the four-drug combination (AN+AD) looks to be very promising in patients with early-stage Hodgkin lymphoma.
Is it a standard yet? Nope. Is it exciting? Definitely. It’s early data. We need to see longer follow-ups and see that compared in a rigorous fashion to older traditional treatments. But the treatment looks to be safe and effective. If we can cure more people and continue to avoid the risk of lung injury with bleomycin, that will be progress.
Your doctor will be able to guide you best in choosing the right treatment if they know you and your priorities best.
Dr. Matthew Matasar
How can patients be involved in treatment decision-making?
I encourage patients to talk with their doctors before and as they’re choosing a treatment together to make sure that the doctor understands their priorities. All of these chemotherapy programs have risks and side effects. Your doctor will be able to guide you best in choosing the right treatment if they know you and your priorities best.
We teach our student doctors and our doctors in training to do this. There’s a program with the best outcomes, but the differences can be minor. If the risks with a certain program are unacceptable, then it’s the wrong treatment even if it has a 1% better cure rate. It’s not right for you as an individual.
You’re not going to give somebody who’s a professional sharpshooter a medicine that has a risk of causing nerve damage to their fingers. Their professional life will be over. Even if it’s the “right treatment,” for that person, it’s the wrong treatment. Everything is in the context of you as a patient. You have to share that openly and candidly with your doctor so you can choose well together.
If your doctor says you’re taking up too much time, you have the wrong doctor. That is unacceptable. I believe in my heart that no doctor actually feels that way. We’re all in this to win this. We show up to work every day because we want to cure people and care for people. Period.
Don’t feel that you’re burdening your doctor. We do our job best when we communicate most clearly and most authentically with our patients. I need to know you as well as possible if I can be the best doctor for you.
I’ll tell my patients that I’m their Sherpa. I’m the guy lugging the bags up the mountain. This is your mountain climb. This is your journey. I’m here to guide the way. I can’t do that if I don’t know you and if you’re not authentic with me.
Radiation treatment, effective though it may be, comes with risks. Those risks can be both short-term and, more importantly, long-term.
Dr. Matthew Matasar
What is the role of radiation in the treatment of Hodgkin lymphoma?
Radiation therapy continues to be a very effective treatment in managing Hodgkin lymphoma but one that we continue to try to constrain the use of. We understand that radiation treatment, effective though it may be, comes with risks. Those risks can be both short-term and, more importantly, long-term depending on where the radiation beam is shined.
Radiation is good at treating and killing cancer cells, particularly Hodgkin cancer cells, but it also touches tissue in the area where the beam is shining. If it’s shining near your heart, your doctor needs to be thoughtful about the risk of subsequent heart disease later in life after you’ve been cured. The same goes for any part of the body.
When you’re considering radiation treatment, you want to have a thorough and informed discussion with both your medical and radiation oncologists to understand what their understanding is of your personalized late-effect risk given the dose, where the beam will shine, and your personal characteristics.
Some studies are now being deployed and developed to try to develop the next-generation immunotherapies that could hold promise for our patients.
Dr. Matthew Matasar
Are there upcoming treatments for Hodgkin lymphoma that patients need to watch out for?
An area of both unmet need and promise is: what do we do when all of our current excellent treatments have failed? Thank God this is not common. We have a very broad and very encouraging treatment armamentarium. We have a lot of tools in the bag.
Despite that, there are still situations when all of our treatments fail patients, including this family of immunotherapies, these checkpoint inhibitors. What do we do when even checkpoint inhibitors have failed our patients? What’s after that has been our question.
Some studies are now being deployed and developed to try to develop the next-generation immunotherapies that could hold promise for our patients, even when our current treatments have failed. We don’t have data on those yet, but we’re seeing those studies being described, developed, and opened. We’re seeing that at ASH and that’s encouraging.
One study we have open at Rutgers is next-generation immunotherapy, a drug called favezelimab. This targets a different mechanism of immune activation. It’s being looked at in combination with checkpoint inhibitor treatment in patients who have been failed by checkpoint inhibitors alone, hoping that this dual immunotherapy could work even when single-agent immunotherapy has failed.
For people who’ve been failed by good first treatment, if they’re fit and eligible, receive an autologous or from-self stem cell transplant.
Dr. Matthew Matasar
When is stem cell transplant considered for a patient with Hodgkin lymphoma?
The way that we often approach Hodgkin lymphoma is we give good first treatment with the hope and usually expectation of cure. Despite that, a smaller percentage of patients will be failed by that treatment and require additional therapy.
For people who’ve been failed by good first treatment, if they’re fit and eligible, receive an autologous or from-self stem cell transplant. That treatment can cure patients even after being failed by traditional chemotherapy. How to get people to and through that treatment is a little bit individualized, but it’s generally seen as a two- or three-step approach, sometimes described as a triple jump.
Step one is to get the disease into remission and shrink it down. We do that with chemotherapy, immunotherapy, or a combination. How best to do that first jump is very personalized.
Once somebody is in remission, God-willing, then they go into step two, which is the stem cell transplant itself. What that is fundamentally is a round of high-dose chemotherapy with or — increasingly — without radiation as part of that.
A small percentage of your body’s stem cells, which are filtered out of your blood, are collected and frozen. You get six days of intensified chemotherapy. On the seventh day, you rest. Your stem cells are thawed and given back to you as an antidote to the chemotherapy to allow you to recover quickly.
Part of the problem with high-dose chemotherapy is that it wipes out, God-willing, every last of those Hodgkin cells, but it also will temporarily empty your bone marrow.
Dr. Matthew Matasar
How does using your stem cells help treat the cancer?
Part of the problem is calling this treatment a transplant. It’s a misnomer. There’s no transplantation going on. When we write about this, what we use is high-dose therapy with autologous stem cell rescue. What that translates to is a round of intensified chemotherapy and giving your stem cells as an antidote to the chemotherapy.
Part of the problem with high-dose chemotherapy is that it wipes out, God-willing, every last of those Hodgkin cells, but it also will temporarily empty your bone marrow because those cells are sensitive to that chemotherapy.
By giving you your stem cells back, those cells know what to do. They go back to the bone marrow space that’s been temporarily emptied by the chemotherapy. They’re seeds planted in fertile soil. They start to grow anew and allow you to start making new blood cells, typically about 10 days later.
The treatment with an allogeneic transplant is a little bit of a tightrope walk.
Dr. Matthew Matasar
When do you use your stem cells versus a donor’s?
There are two different types of transplants. There’s the one that is called autologous or from yourself, which is not a transplant. It’s an antidote.
A situation when you’re doing a donor stem cell transplant is called an allogeneic transplant or from someone else; that’s a transplant. You are transplanting someone else’s immune system into your body.
That’s a very different treatment with very different purposes. The donor stem cells are the treatment because what we’re asking those cells to do is to make a new immune system and have that new immune system prevent the cancer from coming back. It is the ultimate immunotherapy.
An allogeneic stem cell transplant has risks and rewards along with it. It’s great. It can cure Hodgkin lymphoma even when chemotherapies have failed. That’s very powerful. But that new immune system needs to be managed.
The treatment with an allogeneic transplant is a little bit of a tightrope walk. If the new immune system gets too active, it can start attacking not just cancer cells but healthy cells. That’s graft versus host disease (GvHD) when the new immune system attacks your body.
If you suppress that immune system to keep it from being so hyperactive and injuring healthy cells, now your immune system is lowered and you’re at risk for infections. It’s a balancing act and that’s the challenge with donor transplants. And that’s why specialists do this.
Ask for a second opinion. Don’t worry about offending anyone or hurting their feelings.
Dr. Matthew Matasar
How can a patient advocate for their health?
This is an important point and a great challenge. There is a lot of different care given in this country. Some of it is excellent and some of it is less. There’s a lot of inequality and inequity that comes from that observation, but it’s the truth of it.
I worry that patients are uncomfortable, shy, or defer to their doctors. They don’t want to be a squeaky wheel or hurt anyone’s feelings. This is nonsense. This is your journey and this is your life.
Ask your doctor: How up-to-date are these data? How do you keep up to date? How did you arrive at this decision? Is my case reviewed at a tumor board or with your colleagues or are you making these decisions in a vacuum? Where would you recommend I get a second opinion? If it’s a community center, should I go see an expert? The answer is often yes.
A good community oncologist gives excellent care nine times out of ten and will welcome a second opinion from a local academic expert because it gives them additional confidence and support and reassures the patient that they’re getting good care. We all want our patients to be confident in and comfortable with the care they’re receiving.
Be a squeaky wheel. Ask for a second opinion. Don’t worry about offending anyone or hurting their feelings.
Immunotherapy is effective, active, and powerful in Hodgkin lymphoma.
Dr. Matthew Matasar
Will we see the use of bispecific antibodies and CAR T-cell therapy in the treatment of Hodgkin lymphoma?
Truthfully, not yet. It’s an interesting question why. In many ways, we see that immunotherapy is very powerful in treating Hodgkin’s lymphoma. This family of checkpoint inhibitors helps a lot of different types of cancer. They can help non-Hodgkin lymphoma and other types of cancer sometimes.
They don’t work in any disease better than they work in Hodgkin’s. Hodgkin’s is the paragon. It’s a shining example of how these treatments can help patients.
We know immunotherapy is effective, active, and powerful in Hodgkin lymphoma. Why haven’t we been able to develop CAR T and bispecifics in this disease? I don’t know, but we’re working on it.
All these lymphomas are unique illnesses with their unique ways of behaving. They range from very slow-growing illnesses to very fast-growing illnesses and everything in between.
Dr. Matthew Matasar
What is the difference between Hodgkin lymphoma and non-Hodgkin lymphoma?
Lymphoma is not one disease. There are more than 100 different types, all of which come from lymphocytes or immune cells.
One of these lymphomas is called Hodgkin lymphoma and the others are very creatively called non-Hodgkin lymphoma. Why? Because they’re not Hodgkin lymphoma.
All these lymphomas are unique illnesses with their unique ways of behaving. They range from very slow-growing illnesses to very fast-growing illnesses and everything in between.
We generally lump them into two families, one that we call indolent or more naturally slow-growing and aggressive or more naturally fast-growing. These tend to present a little bit differently.
The most common way to find an indolent lymphoma is accidentally doing testing for other purposes. Let’s say a patient had a kidney stone and got a CT scan and there were some small swollen lymph nodes in there. A biopsy is done and, lo and behold, they find lymphoma that wouldn’t have been found if it weren’t for these other tests.
Aggressive lymphomas tend to make people sick and announce themselves. Swollen glands, a new lump, or symptoms like fevers, drenching night sweats, unexplained weight loss, progressive profound fatigue, pain, something wrong that is new, persistent, and progressive — those lead people to go and see a doctor to see why.
Common symptoms for patients with a new diagnosis of Hodgkin lymphoma can also include shortness of breath, progressive fatigue, and drenching night sweats.
Dr. Matthew Matasar
What are the symptoms of Hodgkin lymphoma?
Hodgkin lymphoma has unique symptoms that are traditionally associated with it. Most commonly, it’s swollen glands, typically in the neck or the armpit than in the belly or groin.
Common symptoms for patients with a new diagnosis of Hodgkin lymphoma can also include shortness of breath, progressive fatigue, and drenching night sweats.
There’s a specific and uncommon but peculiar symptom of feeling pain right after drinking some alcoholic beverage, oftentimes in the middle of the chest. If you have that symptom, it always turns out that you have Hodgkin lymphoma. It’s almost diagnostic of this disease. I don’t know why, but it’s the truth.
Itchiness is not an uncommon way for Hodgkin lymphoma to announce itself. There’s all these traditional stories that we all know. A common story leading to a Hodgkin’s diagnosis can be, “I’ve been itching for the last 12 months. I saw my internist and they sent me to an allergist. They did a skin biopsy and put me on antihistamines. They helped for a little while, but then I got itchy again. They gave me steroids and that helped. I stopped the steroids and got itchy again. Finally, somebody said, ‘Maybe we should do an X-ray or a CAT scan or something.’” Then they find out it’s been Hodgkin’s all along.
When patients ask me what the correlation is between itchiness and lymphoma, I say it’s evil humor. It’s something that the Hodgkin’s is secreting into the body to cause itchiness. We don’t know what that substance is, but it’s a real thing.
If you’re not getting a satisfactory answer, if you’re continuing to feel unwell, you need and deserve to know why.
Dr. Matthew Matasar
What can patients do when they’re having symptoms and feel like something is wrong?
This is challenging because doctors’ brains are trained to seek the most likely answer. There’s a phrase that everybody hears in medical school that goes, “When you hear hoofbeats, think horses, not zebras.”
Common things are common. If you’re an internist, if somebody is itchy, nine times out of ten, chances are it’s because they have a new detergent, eczema, or some seasonal allergy. It’s usually not Hodgkin’s. It’s not a common disease.
From the patient’s perspective, you need to not take no for an answer. If you’re not getting a satisfactory answer, if you’re continuing to feel unwell, you need and deserve to know why. Ask for additional testing or additional referrals until somebody can figure out why.
There’s this family of not very well-understood, illnesses called paraneoplastic syndromes.
Dr. Matthew Matasar
What’s the most unusual Hodgkin lymphoma symptom you’ve seen?
Some rare but awful things can be symptoms of Hodgkin lymphoma or other lymphomas. There’s this family of not very well-understood, illnesses called paraneoplastic syndromes. It means some sort of illness that’s being caused by the cancer but not from the cancer.
A range of paraneoplastic syndromes can occur. Some of these can be very, very devastating, including neurological or even brain illnesses that are caused by the body’s reaction to the cancer in an indirect fashion. They can be very confusing because they’re very rare and can be devastating.
Hopefully, a diagnosis will be made. Paraneoplasia usually gets better when the cancer gets better. Not always, but usually.
A scan never diagnoses cancer. The only thing that diagnoses cancer is a pathologist.
Dr. Matthew Matasar
How is Hodgkin lymphoma diagnosed?
Often, when somebody meets me, it’s because they’ve been diagnosed with lymphoma already but not always. Sometimes people will be referred for an evaluation to guide that diagnostic process because somebody is worried that it could be Hodgkin’s.
There’s a very clear process for how you go about diagnosing Hodgkin’s lymphoma. You have a clinical suspicion that leads to imaging, which will then show swollen glands or other growths that are suspicious of Hodgkin’s lymphoma or some other illness.
A scan never diagnoses cancer. The only thing that diagnoses cancer is a pathologist, a doctor who looks at a diagnostic-quality biopsy specimen under a microscope.
Lymphomas are cancers of lymphocytes; that’s a biological term. Leukemia means cancer in the blood. It’s a geographical term.
Dr. Matthew Matasar
What is the difference between lymphoma and leukemia?
This is a point of confusion because these terms get bandied around a lot. Lymphomas are cancers of lymphocytes; that’s a biological term. Leukemia means cancer in the blood. It’s a geographical term. It doesn’t tell you anything about what type of cancer it is.
You can have breast cancer that is in the leukemic phase, meaning it’s a breast cancer, but it’s spread into the bloodstream. You can have prostate cancer, in the leukemic phase. You can have lymphomas that are leukemic lymphomas. Chronic lymphocytic leukemia is a lymphoma that is leukemic. It’s a lymphoma in the bloodstream.
Other types of leukemia are not from lymphocytes but from other types of immune cells. The most common of those is acute myelogenous leukemia or AML. That’s a type of leukemia that comes not from lymphocytes but from myelocytes, a different type of immune cell.
As far as symptoms, how do lymphoma and leukemia differ?
Leukemia is a geographic description. Some leukemias have no symptoms. You show up for a routine blood test and the doctor sees something and refers you to a hematologist.
Some types of leukemia make people very, very sick very quickly: progressive fatigue, weight loss, and a loss of appetite. What doctors very unpleasantly label failure to thrive, which means the patient is sick and getting sicker.
Follicular lymphoma is an indolent, slow-growing lymphoma. Most commonly, people with follicular lymphoma will be diagnosed before they ever have symptoms.
Dr. Matthew Matasar
What is follicular lymphoma?
Follicular lymphoma is most common in America and similar countries. It’s the most common slow-growing form of lymphoma.
It’s called follicular not because of hair follicles but because of the stage we think that lymphoma develops. As lymphocytes grow up or mature, they transit through a lymph node. Lymph nodes have these little follicles in them, which are areas where lymphocytes train how to fight infections and mature. While they go through those little follicles, we think that’s the step at which the mutation occurs.
What symptoms are associated with follicular lymphoma?
Follicular lymphoma is an indolent, slow-growing lymphoma. Most commonly, people with follicular lymphoma will be diagnosed before they ever have symptoms. For example, they go for a routine mammogram and the breast tissue is healthy, but there’s a swollen gland in the armpit. That will lead to a biopsy and the biopsy will show follicular lymphoma. Any number of stories like that.
Sometimes people will have follicular lymphoma and be sick from it. The most common symptoms would be progressive fatigue or if a lymph node is growing in a spot that’s pushing on a nerve, it may cause pain.
Is follicular lymphoma genetic?
Follicular lymphoma is a genetic illness insofar as we think that it arises from randomly occurring mutations in those lymphocytes in the majority of patients, but it’s not genetic in terms of hereditary.
It’s not passed on from parent to child in a direct fashion. If you’re diagnosed, your children don’t typically need to be screened or tested to see if they’re at risk for follicular lymphoma. If you have a family member who was diagnosed with follicular lymphoma, it doesn’t mean that you need to go and get a screening test of any sort.
The only one I would actively screen for is a rare form of T-cell lymphoma called either ATLL (adult T-cell leukemia/lymphoma) or HTLV-1-associated leukemia/lymphoma.
Dr. Matthew Matasar
Are there any lymphomas or leukemias that require genetic screening?
Never say never. There’s a lot of variety in my world and there are some illnesses that have a more clear familial relationship.
The only one I would actively screen for is a rare form of T-cell lymphoma called either ATLL (adult T-cell leukemia/lymphoma) or HTLV-1-associated leukemia/lymphoma. It’s an uncommon form of lymphoma in America that’s caused by a virus that can be passed from parent to child.
Not everybody with that virus will develop lymphoma, thank God. But if there’s a parent who develops ATLL associated with HTLV-1, some experts might consider screening children to see if they carry the virus. Whether they need to be screened for lymphoma if they do have it is unknown, but that’s information that some families will choose to seek.
For most forms of lymphoma, even stage 4, which means it’s in lymph nodes and other tissues, is not the bad news that it is with other types of cancer.
Dr. Matthew Matasar
What is staging in lymphoma?
Staging means where the cancer is in your body. The stage for some types of cancers is super important, like breast cancer, lung cancer, and colon cancer. For cancers that start in an organ in the body, the stage is king. Stage 1 means we got it early and stage 4 is often a challenging conversation.
The stage of lymphoma is not as important. For most forms of lymphoma, even stage 4, which means it’s in lymph nodes and other tissues, is not the bad news that it is with other types of cancer.
Stage 1 typically means involving lymph nodes in one area in the body, like the left neck or the right groin.
Stage 2 means multiple lymph node areas but on one side of the body. Stage 2 is lymph nodes either above or below the diaphragm.
Stage 3 is lymph nodes above and below the diaphragm.
Stage 4 is in lymph nodes and other parts of the body, like some other tissue, the bone marrow, or an organ like your lung, liver, or skin.
What is Burkitt’s lymphoma?
Burkitt lymphoma is a less common form of highly aggressive non-Hodgkin lymphoma. There are three different types of Burkitt lymphoma.
One is endemic Burkitt lymphoma and this is usually found in children in Africa. It’s associated with infection with both Epstein-Barr virus and often malaria. It typically shows up in children with a very large mass in the jaw, sometimes with illness throughout the body. In America, that’s much less common, thankfully.
The two types that are more common in America are sporadic Burkitt’s and a secondary form, which is associated with HIV, is immunodeficiency-related Burkitt lymphoma.
