High-Risk Smoldering Multiple Myeloma Highlights from ASH 2022
What Newly Diagnosed Patients and Caregivers Need to Know
Jack Aiello
Multiple myeloma patient advocate Jack Aiello has been living with myeloma for 28 years.
In this conversation, he speaks with Dr. Shaji Kumar, a hematologist at the Mayo Clinic whose research focuses on the development of novel drugs for the treatment of myeloma.
They discuss the difference between smoldering myeloma and active myeloma, the determining factors of high-risk patients, and what high-risk smoldering patients can do to delay or possibly avoid progression to active myeloma.
Dr. Shaji Kumar
This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Jack Aiello: I’m with The Patient Story. I’m a myeloma patient and have been for 28 years. I have followed this field very closely and always know that there’s more to learn.
Dr. Shaji Kumar: I’m a hematologist at Mayo Clinic in Rochester, Minnesota.
What is smoldering multiple myeloma?
Jack: Around 30,000 oncologists, researchers, physicians, pharma reps, and more from around the world attend the annual American Society for Hematology conference, also known as ASH, to hear the latest myeloma research from clinical trial investigators, like Dr. Kumar.
We’re going to primarily focus on a topic of myeloma called smoldering myeloma and that’s important because it’s a precursor to myeloma, although you may have never been diagnosed as smoldering.
Dr. Kumar, can you explain the differences between smoldering myeloma and multiple myeloma? And what determines high risk for smoldering vs. high risk for myeloma?
Dr. Kumar: With myeloma, we have precursor stages that clearly exist before patients actually get active multiple myeloma.
What we have learned is that the process that eventually leads to [the] development of active myeloma probably happens sometime in the 30s for many patients. We think it takes an average of about 15 years for that initial seed, so to speak, to grow into a stage where it is actually creating problems like active multiple myeloma does.
There are two distinct stages within this precursor phase. One of which is called monoclonal gammopathy of undetermined significance, essentially saying that you can find that initial condition. We can find some abnormal plasma cells, but they’re quietly sitting in the bone marrow, making protein that we can detect in the blood, which allows us to identify and diagnose this condition, but not really doing any major damage that we are aware of. We know that in some people, it can lead to some symptoms other than what we see in myeloma.
It’s important to note that this monoclonal gammopathy of undetermined significance is not something that is uncommon and certainly increases with age. In fact, if you take 100 people who are 70 years or older, you’re probably going to find that eight to ten of those people will have a monoclonal protein in their blood, suggesting that they do have this early condition that is sitting there.
We also know from long-term studies that [for] the vast majority of the people, eight out of ten people with that monoclonal gammopathy, it will amount to nothing. People will just live their normal life, a normal length, without it ever becoming a problem. But for the other two out of the ten, it can evolve into something that needs something to be done to it and that is often multiple myeloma.
When patients develop multiple myeloma, clearly they have damage to their body because of this abnormal group or collection of plasma cells or myeloma cells which have become cancerous. They can destroy the bone, produce high amounts of protein that get deposited in the kidneys and cause renal failure or kidney malfunction, can cause high levels of calcium, [and] can cause people to be anemic.
In some people, we can certainly identify them before these things happen or identify them at a stage where these things are very imminent and we can start treating them. But those definitions overall together [are] what you would call active myeloma or symptomatic myeloma that clearly needs treatment.
Wedged in between active myeloma and monoclonal gammopathy of undetermined significance or MGUS are people with what we call smoldering multiple myeloma. These are patients or individuals where the amount of plasma cells or proteins [has] progressed to a point where there is [a] considerable amount of those cells in the bone marrow, typically defined as more than 10% or an M protein in the blood that’s more than 3 grams.
Over time, what we have learned is these people are in between the markers and myeloma; [it] is not a distinct diagnosis, so to speak. It’s more of a collection of people who truly has more MGUS or more myeloma. We just can’t do one test and say you are more myeloma-like or you are more MGUS-like. We just have to depend on time for things to declare itself.
For at least half or two-thirds of people with smoldering myeloma, it is okay to sit and wait, but the other third may be at a higher risk of progressing. Those are the individuals [whom] we really think we could do something with the treatments we have and actually make a difference.
When we say make a difference, we mean [delaying] the time they actually get active myeloma, maybe [preventing] them from ever getting active myeloma, or maybe [curing] some of those people and we can just forget that they will ever get myeloma and not even worry about it again.
How do we identify those people? We need to be able to get to them in as precise a fashion as we can. We want to limit the number of people who might get exposed to these treatments, which may not have the same benefit [to] others.
One of the ways we do that is to use the International Myeloma Working Group criteria. Laboratory markers tell us the risk of that individual getting active myeloma in the next two years. If you think it’s more than [a] 50% chance, we feel like we need to do something about it.
There have been large phase 3 trials that have been done, which clearly show that there is a rationale for intervening in those people.
The difference between smoldering myeloma & multiple myeloma
Jack: You’re saying there is a method to determine high-risk smoldering. What’s the difference between them?
Dr. Kumar: We are talking about a stage that you may or may not have gone through. Not everybody has to be in a smoldering stage before they go from markers to myeloma, but many would have gone through the stage.
What we are trying to do here is to see [if] we can do something different for future patients, a course that is different than what you all went through.
The most critical thing that is different is, of course, whether it’s doing damage to your body — bone lesions, kidney problems, anemia, high calcium — or not. There are some individuals who may not have those characteristics, but the risk of getting that is very high: 80% plus in the next two years. Those people, we already consider as active myeloma and not smoldering anymore.
Jack: High-risk myeloma patients are more determined by mutations of certain chromosomes and things like that, right?
Dr. Kumar: That is right. When you talk about high-risk multiple myeloma or active myeloma, we’re talking about people with chromosomal abnormalities (translocations or 17p deletion), high LDH levels, or if they have stage 3 [based on] the International Staging System.
What is the ASCENT trial?
Jack: At ASH, you presented abstract 757 on the ASCENT trial for high-risk smoldering myeloma patients. What was this trial about?
Dr. Kumar: When you think about doing something different with people with high-risk smoldering, what’s our ultimate goal? We want to make sure they never get myeloma and they never have to get myeloma-type treatment that is often given continuously for long periods of time.
There are two approaches. One is obviously to give less intense treatment than what we do in myeloma and try to kind of kick the can down the road, so to speak. The other option is since we caught it so early, to see [if] we actually just get rid of it completely and maybe never even worry about it.
The former approach is what has been taken in the large phase 3 trials that the Spanish group did [and] the cooperative group in the US did. Both trials showed that people with high-risk smoldering myeloma, if you treat them with lenalidomide or lenalidomide and dexamethasone — far less intense than the three- and the four-drug combinations we use for patients with active myeloma — those interventions actually delay the progression to myeloma and, in fact, make people live longer.
What we’re really trying to do with the second approach is trying to cure the disease. There have been some trials looking: can we use more intense treatments and give it for [a] short duration to try and get rid of those myeloma cells?
The Spanish group did a trial called the CESAR trial, which was also updated at ASH [2022]. They treated people with the combination of carfilzomib, lenalidomide, and dexamethasone (myeloma-type treatment), did [a] transplant (this trial only included transplant-eligible patients), and then get them on maintenance treatments like what we would do for myeloma but give it over a defined period of three years instead of giving it continuously until [the] disease comes back.
With a longer-term follow-up [of] four-plus years, what they have seen is only five of the 81 or so patients that they enrolled have progressed to active myeloma. [For] many of those people who have progressed, the progressions have been predominantly just biochemical, meaning the M spike goes up [but] they don’t actually get myeloma.
What the ASCENT trial did was take a slightly different tact. Knowing that a significant number of people cannot go do a stem cell transplant, instead, we will do a monoclonal antibody, like daratumumab added to carfilzomib-len-dex. We use carfilzomib, lenalidomide, daratumumab, and dexamethasone for 12 cycles and then gave them maintenance for 12 cycles for daratumumab and lenalidomide. Basically, two years defined duration of treatment in patients with high-risk smoldering myeloma.
What we found was these results are quite similar to what we have seen in [a] myeloma setting. We get deep responses. Almost two-thirds of the people actually get what we call a stringent, complete response, meaning we can’t really see any protein. We can’t really see any myeloma cells under the microscope.
More importantly, nearly two-thirds of the people who got there also were minimal residual disease negative. We cannot even detect myeloma cells in the bone marrow by using highly sensitive approaches. It seems like this approach does manage to eradicate at least a significant proportion of the myeloma cells in the bone marrow.
The question that’s going to be really critical for us is: does this eradication mean that these cells will not grow back like what it does in myeloma? Only time will tell. I think both studies will continue to follow these patients over a long period of time to see if this emerging activity that we have seen is something that can be sustained over a long period of time without continued treatment.
How long until SMM patients are cured?
Jack: How long do you think you need to follow these patients before you can say these patients are cured?
Dr. Kumar: That is a good question and I don’t know if we all know the right answer to that. But the longer we can go without the disease coming back, I think the higher the probability that we may have actually eradicated this.
I’m just going to put a number out there. If in 10 years from the start of the treatment — that means eight years without any treatment — the myeloma hasn’t reared its head back up, I think I would call it successful. Obviously, each passing year is more and more of a success.
Jack: I guess we hope to see some plateau of the curve where people are no longer relapsing if you will.
Dr. Kumar: I think that is going to be the key because, in myeloma, we know that even if they get to be MRD negative, that curve never becomes flat. People continue to kind of fall off because of myeloma coming back. We’re hoping that it would be a different picture here, like what we see with some other hematological cancers like lymphoma and so forth.
Are there still trials open for high-risk smoldering patients?
Jack: At the IMF ASH symposium, Dr. Vincent Rajkumar said that treatment for all high-risk smoldering patients should either be Revlimid with or without dexamethasone or a clinical trial. Do you agree? Are there still trials open for high-risk smoldering patients?
Dr. Kumar: Yeah, I completely agree. We have to always build upon what we have learned and what we have learned in smoldering from two large trials that doing something is better than not doing anything. Giving them at least lenalidomide or lenalidomide with dexamethasone [not only] prevents the myeloma [from] coming back, [but] the Spanish trial has actually made people live longer. We owe it to our patients to have that discussion about the choices.
Ideally, if I had the option, I would definitely put everybody on clinical trials rather than using that treatment because there’s so much more to be learned. We don’t know if lenalidomide-dexamethasone is the right approach. Should we treat them like myeloma with three drugs, which is the focus of the ECOG trial?
The SMM trial is currently enrolling so that is a trial that can be considered. There’s [an] isatuximab trial that is currently accruing looking at isatuximab-len-dex versus len-dex. There [are] also multiple smaller trials in different institutions that are looking to try and see: are there specific combinations or specific drugs that might actually provide a meaningful benefit for patients with high-risk smoldering? It remains an area of active investigation so I would strongly encourage everyone to consider enrolling in clinical trials.
Asking your doctors about clinical trials (high-risk smoldering patients)
Jack: The important thing for smoldering patients is to ask their doctors: are they considered high-risk smoldering or not high-risk smoldering? If they are high-risk smoldering, they should be asking their doctor about trials. Most of these trials that you just mentioned can actually be done locally. They don’t necessarily, I think, have to be done at major cancer centers. Is that correct?
Dr. Kumar: That is right. That’s especially true for the cooperative group trial like the one we have in ECOG. It should be open in pretty much all the community cancer centers across the country.
Conclusion
Jack: Thank you so much. I’ve learned more about smoldering as well. As I said, you can always learn more about myeloma and different avenues of myeloma treatment. Any final takeaway from ASH that you want to mention?
Dr. Kumar: There’s a lot of data presented at ASH. Spanning all the way from simple questions like, “Should we be doing a bone marrow in patients with MGUS?” to obviously, “How do we treat those people or new drugs that would be potentially effective in people who have seen it all?” It’ll probably take hours to go through all that important data.
There are so many new therapies that are coming through that are so effective, especially immune therapies. We started seeing some of those being employed in the first-line treatment and the first relapse. In five years, the treatment of myeloma is going to look very different than what we are doing today.
Jack: Dr. Kumar, it’s always a pleasure talking with you and I want to thank you so much for providing your insights to The Patient Story.
Vickie was diagnosed with muscle-invasive bladder cancer at 66.
She was initially experiencing intermittent pain but after being told that she did not have a urinary tract infection, she knew she had to keep pushing for answers.
Margo, also a bladder cancer patient, talks with Vickie as she shares her journey of how advocating for herself helped save her life.
This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Name: Vickie D.
Diagnosis:
Bladder cancer
Initial Symptoms:
Intermittent pain in the gut and burning sensation
Treatment:
Chemotherapy: dd-MVAC (dense-dose methotrexate, vinblastine, adriamycin, and cisplatin)
Surgery: cystectomy
It did not surprise me when I got that phone call that it was a tumor. What surprised me was that the only way out was to do chemo and have my bladder removed.
All of us are doing what we can to increase awareness of bladder cancer… to help bring this conversation to normalcy and share stories, hope, and inspiration for others going through it.
Margo W.: I’m a bladder cancer patient who is still cancer-free because I had access to great doctors [and] because I advocated for myself.
We know a fair amount about other kinds of cancer, but not so much about this one. Cancer is not something you want to learn about if you don’t have to so we all have big gaps in understanding what the journey is going to look like.
I had the opportunity to meet and talk with other patients. I love that I get to interview Vickie. She can share her experience and how much it meant to her that she had a bladder cancer mentor who [can] show her what life after [having] your bladder removed looks like. It’s not as terrible as you fear. You have no idea what to expect so that’s why I think it’s so important to share these stories.
We all have some similarities in our stories, but we also have unique experiences. One of the most valuable things to do is to help people not feel alone and to remove a lot of the fear [and] the unknown so that we can see ourselves making it through that journey, get to the other side, and get back to living life.
I hope what it does is inspire and help people feel connected, understand, and reduce fear as we face a variety of different battles.
Vickie, if you had to describe yourself to someone who’s never met you before cancer, how would you describe Vickie?
I was diagnosed in the fall of 2020. I was 66 years old.
Before cancer, I was trying to cram as many things as I could into a day, almost aggressively staying busy.
I’m outdoorsy. Tomboy is what they would call me. I have a small lake house. I spend time out there doing projects.
I love the water. I swim, paddleboard, kayak, bicycle, travel, [and] garden. I have some chickens that are pretty fun to have in the city. I live in the middle of Austin, Texas, and I have lived here most of my life.
Margo found me through Dorothy, who is also a bladder cancer survivor. She’s my bladder cancer mentor.
Margo W.: And I met Dorothy and her husband, John, at the bladder cancer think tank in August of ’22. Dorothy and her husband are very involved with BCAN, Bladder Cancer Advocacy Network. They are also Austin-based. They’re working to create more awareness.
All of us are doing what we can to increase awareness of bladder cancer because it is the least talked about of the major cancers. It’s number sixth or seventh most diagnosed in this country. We are doing what we can to help bring this conversation to normalcy and share stories, hope, and inspiration for others going through it.
Pre-diagnosis
Initial symptoms
Margo W.: What made you think about the pain that you were in? What about that told you [that] you needed to keep pushing for answers?
I didn’t feel well and had some pain. The pain was intermittent enough that it was reoccurring. It wasn’t every single day, but it was enough.
I had a doctor’s appointment coming up in September; May 2020 was when I first noticed that the pain was getting to be less intermittent and almost daily.
I did believe I needed to see my gynecologist and not my family practice physician. I realized that I needed to keep pushing until they would see me. But unfortunately, she wasn’t interested in an old woman that was having a little pain.
Margo W.: How did she specifically respond to you?
She responded by saying that all of my tests had always been fine. I hadn’t had any abnormal test results over the years.
Unfortunately, because I was 66, I had seen many gynecologists over the years from having my children. Then as I aged, these wonderful doctors quit taking patients.
‘You do not have a UTI.’ That wasn’t a good answer for me because I knew if it’s not that, then what is it?
This young woman had only seen me once a year before and I guess she’s just going off of all the test results we had discussed and things that had happened in my life.
I said, “There is something wrong. This pain isn’t going away and I don’t believe it’s a bladder infection [or] UTI. I’ve only had one in my life and there’s no blood.” She said, “We’ll go ahead and run that test again [to] make sure it’s not a UTI.”
They ran the test again [and] called me up. “You do not have a UTI.” That wasn’t a good answer for me because I knew if it’s not that, then what is it?
Ironically, the day after my exam, I started seeing blood. I called them right back and said, “I need to see you again. There’s something wrong.” They had me see the assistant and she also said, “You do not have a UTI.” I said, “Then let me see someone else. Who can I go see?” They recommended a urogynecologist.
Seeing a specialist
Margo W.: Your only symptom was persistent, consistent pain and discomfort. You shared it with her. It’s not a UTI.
The gynecologist [was] saying, “I don’t know what it is if it’s not a UTI. I didn’t see any abnormal results from your pap smears. I haven’t seen any other abnormal results. I don’t feel anything.”
I’m freaking out on the table. ‘What do you mean? Why do we need a CT scan? Doesn’t that mean cancer?’ She said, ‘Oh, there’s no chance of you having cancer. That’s an old man, smoker’s disease.’
The next thing was to get that next specialist. I called my friends and no one had a urologist in their phone book. My next step was to rely on this doctor.
I had to call three times to get the name and then the referral. Luckily, the referral was a gyno-urologist. She said, “I don’t think there’s anything the matter here, but just in case, we’re going to take some measurements. We’re going to go ahead and do a CT scan. We’re also going to do a cystoscopy.”
I’m freaking out on the table. “What do you mean? Why do we need a CT scan? Doesn’t that mean cancer?” She said, “Oh, there’s no chance of you having cancer. That’s an old man, smoker’s disease.”
I did smoke for a short while in my 30s, but I hadn’t smoked then for 30-something years. “It’s probably nothing, but let’s do the CT.”
The next step was to make the appointment. No one in Austin could see me for at least two weeks. I finally found a place out in Cedar Park, which is a good 30 miles away.
It was daunting and because it’s COVID, I have no one with me. Everything that I did, I’m completely by myself because no one was allowed with me. I’d have my phone with me and do a conference call.
Diagnosis
Getting the official diagnosis
I was on a trip. The urogynecologist called me up and said, “I have some bad news,” and that’s how she said it. “I can’t help you. I need to refer you to another doctor.” I have a tumor in my bladder. She told me it was about two and a half centimeters and I said, “That’s the size of my thumb. Oh, that’s not good.”
Doctor wasn’t available for two weeks. It’s now [the] end of October. I pushed that appointment up. I said, “No, I need to see this doctor. What’s his next available? Work me in,” so they did. They worked me in and that was November.
That was daunting to see his business card saying that he was not just a urologist, he was a uro-oncologist. I went, “I have cancer.” I’m thinking, Tumor. They get rid of a tumor. I’ve had a benign tumor removed from my breast. I thought everything was fine. He said, “No, let me show you your scan.”
I saw the tumor on the bladder wall. “What does this mean?” He said, “It means, yes, we’re going to do the cystoscopy. We’re going to try to remove it, but it looks like it’s on the wall. And if it’s in the muscle, there’s nothing that we can do but remove the bladder.”
I was by myself. I’m just going, “Please don’t tell me this. I don’t know what that means for my life because I am super active and I don’t want to stop.”
I took his information. I said, “What about a second opinion?” He goes, “Before we get there, I want to do the cystoscopy.” He was putting me out [for] two more weeks. I said, “Nope, I need you to schedule me next time you’re doing this procedure. Please work me in. I beg you.”
He’s 35 years old at the time. He’s my daughter’s age. I’m just going, “I don’t believe this doctor knows what he’s talking about,” but he does. I knew it, but I didn’t want to know it.
We [did] the cystoscopy two days later. He came out and said, “I can’t do anything for you but chemo and remove the bladder.”
I have tried to eat right, stay fit, [and] do everything to be healthy. I always thought it would be a heart attack or a stroke. I had no idea it would be a tumor that I would have to face.
Knowing it was more than a UTI
Margo W.: When you first went to the doctor, the gynecologist said it’s nothing and it [was] not a UTI. What were your feelings at that point?
It was not the news I wanted to hear. I wanted to hear that you can take an antibiotic and the pain will go away. “You need a hysterectomy.” I could handle that. Isn’t that weird?
I could handle someone telling me that [I] need a different operation because I know many, many women that have had a hysterectomy and I’ve watched them go through this process and healing [from] it. You just don’t need the uterus at this age anyway. But the bladder?
Margo W.: Still need one of those. Then you went to the next doctor who was a urologist-gynecologist. She’s the one who said, “No way this is bladder cancer. That’s an old man’s disease.” How did you feel when she told you that?
I felt bad that I had smoked cigarettes in my life. My first thought is, Oh, old man smoker. Well, I’m an old woman and I did smoke, but I haven’t for so long.
Then my brain just went to, I don’t believe her. I believe there’s something much… I don’t want to say much worse because something could be much worse, we know that. Things can be worse. But I thought, I don’t really believe her. I think it is something.
It did not surprise me when I got that phone call that it was a tumor. What surprised me was that the only way out was to do chemo and have my bladder removed.
Going to doctor’s appointments alone
Margo W.: You are doing all of your doctor appointments solo. No one could go with you. What did that feel like?
I’ve always been independent so, at first, that didn’t bother me. But the day that Dr. Laviana said, “You have cancer and this is what has to happen if you want to live,” then I needed somebody. That is the moment I wish somebody had been with me.
I’ve been with my partner for 13 years. We’ve known each other for longer. At that moment, I needed a person so that I could find out, “Is this reality?”
Anyone that’s ever had this kind of news, it’s hard at that moment to say, “Is this really happening?”
I have tried to eat right, stay fit, [and] do everything to be healthy. I always thought it would be a heart attack or a stroke. I had no idea it would be a tumor that I would have to face.
I felt very alone.
After that appointment, I went to UT Dell Hospital and they did the cystoscopy. Mitch did get to sit in the waiting room there. They did allow that.
When Dr. Laviana told both of us this horrible news, I was glad that he was with me. I needed someone else to hear what he was saying. From that moment on, I realized I needed to always have my phone on me so that it could be a conference call if need be.
A couple [of] days later, I told my daughters, which was really hard. I wanted my daughters, Mitch, and my sister, who has been in medicine — she’s not a doctor or a nurse, but she’s been in the field — to hear whatever the doctor was saying. I needed this support group so it wasn’t me trying to jot down every single fact.
I didn’t cry until chemo. Once chemo hit, then I started feeling sad because the changes were taking place.
Reaction to the diagnosis
Margo W.: I feel so comforted knowing there’s another woman out there who’s been through [something] similar. You want to have as many people close to you as you could. You were jotting down what the doctor is telling you. What was that like for you?
This is a business now. My body is my business. I had run a business and I thought I now have to take care of everything. Even though I’ve got these folks that I’m relying on to listen and hear, I have to make these decisions. No one else is going to make them for me.
He told me, “Yeah, you could just go on with your life, but in five years, you’ll be dead.” My imagination [started] running around. I would jump from, Okay, so I just die. I had a good life. All right. Just throw in the towel and have this horrible cancer in my body. But then I thought, I’m not quite there yet. I still have a lot to do. I don’t know what it is, but I have a lot to do.
My daughters are very important to me. We’re very close. They both live in Austin. My partner and I, we’ve traveled. We have great times. We do a lot of volunteer work. I thought, I need to just keep plowing away.
I don’t think I got depressed. I’ve always found a way to not feel that I can’t handle it. I just told myself this is my new job. My new job is Vickie’s body. Clearly, it wasn’t a good business. I didn’t choose this business. There [are] other things I would have rather been doing, but I just hung in there.
I don’t know how else to describe it. I didn’t cry until chemo. Once chemo hit, then I started feeling sad because the changes were taking place. I didn’t care for the way I felt physically. I didn’t have the energy that I always have. I couldn’t even walk a block down the street and I’m used to walking five miles and hiking.
Treatment
What were your treatment options?
Margo W.: It is interesting how it’s a different journey for everyone.That’s interesting that your go-to was, “Okay, I’m going to project manage this. I’m going to science this,” and I get that because part of us just goes into that mode. How did the doctor present to you what your treatment options were and how did you feel when he told you that?
I remember, he said very quickly, “There’s a couple [of] schools of thought about the chemo regimen. Some people even do radiation.” He handed me the BCAN folder, which, of course, I wanted nothing to do with.
I just thought, Oh, no, I don’t want anything to do with this. It was not that it was scary. It’s just I didn’t really want to read it until I had to. Like for a test.
His idea was, “We’ve got UT Dell Oncology here.” He didn’t mention Texas Oncology. He just started automatically saying, “All of this is right here at this facility.” But he’d only been in Austin for two and a half or three months. He didn’t really know all the resources yet.
The interesting thing was, I did say, “How do you feel about a second opinion?” This is after he’s done a cystoscopy and he’s telling Mitch and me, “You have cancer. This is what you have to do.” I said, “How do you feel about me going to MDA (MD Anderson)? Because I’m going.” And he’s like, “Of course, always get a second opinion.”
I was in excellent hands. [I’m grateful] to have modern science and these two facilities so close to us.
After I told my daughters, I reached out to some friends and one of my friends happened to have aunts and even her grandmother that had bladder cancer and they lived into their 90s. I was like, “Oh, Lord, this is good news.” Then she said, “One of my dear friends from Corpus Christi was diagnosed years ago and she’s about your age, Vickie. You need to talk to her.”
That was probably one of the best conversations I had throughout the journey because Toby is the one who said, “Dr. Kamat, he’s the man. He did my surgery 15 years ago,” and told me exactly what she went through. That was eye-opening.
I got in to see Dr. Kamat and all of those teams of people there. It’s daunting, but it’s amazing, the expertise. Even though I think my doctor is an expert and I’m really glad I have him in Austin, I knew I had these folks and that I was in excellent hands.
[I’m grateful] to have modern science and these two facilities so close to us.
Our mutual friend, Dorothy, and her husband dropped by and brought me the BCAN swag bag. We have the Bladder Cancer Advocacy Network’s coffee cup, brochure, and brochures for the whole family. A wristband that I still wear every day, as does Mitch, my partner. That was really good for me to be greeted into this new community of bladder cancer survivors.
They are my earth angels, Dorothy and John, and the whole BCAN network.
Urinary diversion options
Margo W.: We aren’t innately comfortable talking about bladder cancer. We’re ladies. This is below the belt. We talk about breast cancer. We talk about prostate cancer. We talk about colon cancer.
There is a problem with this kind of cancer being misdiagnosed, especially in women. What I love is that you and I are both willing to go out on a limb and talk about something we don’t especially love to talk about.
The neobladder: did the doctor present that as an option? How was that handled?
I was always going to have the neobladder. I just thought, That’s the only way I can do this. I have to have something that’s not external. I’m so active. I don’t want this extra piece of equipment.
I don’t know what I was picturing. I was picturing another set of organs on the outside of your body. And it’s really not that big.
After seeing Dr. Kamat and that wonderful team at MDA, they were saying the exact same things that Dr. Laviana was saying in Austin.
We had to go [to MD Anderson] twice because the first time, they wanted their very own COVID test. We went down on a Sunday, got the COVID test, turned around, went on a Tuesday, and stayed through that Thursday.
Dr. Kamat, bless his heart. What a physician. He wanted all the tests new. He knew what he saw, but he said, “I’m going to go in and I’m going to see what I find.” All the tests were redone.
He and I talked about neo because Dr. Laviana knew I wanted that. As soon as he told me about the neobladder, I was right on it.
Then Dr. Kamat, his group, and the oncologist there, Dr. Campbell, are looking at me going, “Are you sure you want the neobladder because you’re super active? It takes about a year to ever even figure out how to avoid having these accidents. You’ll be wearing a diaper for at least six months and maybe longer. You will [catheterize] yourself daily.”
I had catheters when I had my children. I am done with catheters. I can’t do that. No, I’m not catheterizing. Up until the day of surgery, Dr. Laviana thought I was going to do it. He said, “Oh, neobladder.” I said, “No, I’m not doing it. Too much.”
Margo W.: What is a neobladder?
It is a piece of your intestine. They cut out the little ostomy. They use part of your colon and create a bladder out of that. It fills up and then you would urinate just the same — theoretically — as you would if you still had your bladder.
However, the problem is, especially with women, they’ve now cut through all of those muscles. They’ve pretty much stripped you of any feeling that your bladder is full. My understanding is that it would take the place [of your bladder], but it’s made out of your own body.
The problem would be that at my age, especially, I don’t have [a] strong muscle reaction to something filling up down there. For me, it just probably would have taken two years to ever get that structure back and not void all over myself.
Two women that I’ve spoken to have neobladders. They were in their early 50s when they were diagnosed and they did tell me how difficult it was.
The third option is the Indiana pouch, which Dr. Kamat recommended not doing [because of] your chances of having infections. That’s the other reason I didn’t want the neobladder.
[With] the Indiana pouch and the neobladder, your chances of having numerous infections the rest of your life, like UTIs, it’s a great percentage.
The last part of that is you can get cancer in your neobladder or the Indiana pouch. I thought, If I’m going to do this, I’m going to try to erase all chances as much as possible.
Margo W.: Can you describe what an Indiana pouch is?
As far as I understand, from the people I’ve spoken with, they also take a piece of your intestine. They’re hooking up your ureters to another piece of your intestine. But instead of it coming out for an ostomy pouch, it stays within your gut.
It is similar to the neobladder, but you do catheterize at least twice to three times a day to void your urine.
Whereas anyone that has an ostomy and the little pouch, you just feel it. “Okay, it’s kind of full. I’m using the restroom,” wherever you are.
Margo W.: Funny question: what’s the best thing about having a urostomy?
I did a five-mile hike in the woods. My friend that I was with [had] to use the restroom. I’m like, “I’ll go and use the restroom, but I don’t have to because I’m out in the woods,” and I just walk behind a tree. There’s no more squatting and I like that.
I like that I don’t have to touch a toilet and that’s the best. My friends all know what my body is now. We all joke about it. “Vickie doesn’t have to use the restroom. She can just go behind a tree.”
I could have gone to the hospital but I liked coming home and being in my little world.
Chemotherapy for bladder cancer
Margo W.: Talk to me about chemo and what you ended up doing. How long you were in? What was that like and how did you feel about it?
The one that I wanted was the dd-MVAC (dense-dose methotrexate, vinblastine, adriamycin, and cisplatin). You go in one day and they give you two of the drugs. Then you go in the second day and they give you the rest of them. That’s for two months, two times a week, every other week for two months.
I went to Texas Oncology. I was very fortunate that Dr. Campbell, the oncologist at MDA, was a resident with Dr. Yorio at Texas Oncology so he actually got my appointment.
I was just about to start it with UT Dell. They didn’t even have the drugs on hand. They were going to have to order it.
They did the port. After a while, especially [with] these drugs, you might have trouble finding that vein.
I picked that one over the other regimen. The other regimen was for four months, I believe, and you do the same thing every other week. However, you don’t lose your hair. It’s not as intense, but I wanted to get rid of this tumor and they said the best way to do it is to use this heavy, dense dose.
Again, I was really glad about modern science because I know that a couple of years ago, and at MDA they still do this, you are in the hospital when you receive your chemo treatments.
I could have gone to the hospital but I liked coming home and being in my little world. [There] was COVID again and no one could go into Texas Oncology with me. I would just sit there and freeze. It was winter. It was so cold.
Besides the surgery, I think that was the most frightening part of this experience. MDA was daunting and frightening [with] all the tests being done there by myself. Going into Texas Oncology by myself, walking up the steps, and seeing all the patients was very, very, very hard.
I was so sick [that] I couldn’t stand food. Just looking at it…
Side effects from chemotherapy
Margo W.: How long was each session of chemo? How did you feel after?
Day one was about five hours and day two was about eight.
I lucked out. [The] very first day that I went to Texas Oncology, I had a nurse. She was this little firecracker. She was giving me all these facts and saying, “This is what exactly is going to happen. In 14 days, you will lose your hair. In a couple [of] hours, you’re going to feel like this.”
I made this joke about [a] John Prine song where when I go to heaven, I’m going to have a ginger ale and vodka. He has this wonderful song about dying and what’s going to happen when he goes to heaven.
She just said, “I want you to go home and have a ginger ale and vodka tonight.” I was like, “But I’m not drinking. I’m trying to save my organs.” And she goes, “No. You need to because you’re a nervous wreck, I can tell, and this will help.”
I got ahold of my partner and said, “Hey, Mitch, stop at the store and get me a ginger.” I was drinking ginger ale anyway, but it was just funny how that was my first day.
My first impression [was if] this is what it’s going to be like, no problem, right? That first treatment, I went, “Well, that’s not too bad.”
Then I saw that I was going to take seven other pills. Again, modern science [is] amazing. In the hospital, they’re going to give it to you on IV but the second you get home, you start taking these pills and you do that every other week.
I’m taking all these pills. I hate pills, but I’m going to take them. One of them, she said, “You’ve got to take it,” because it was the steroid, I believe. “It’s going to help your immune system. You’re going to feel weird,” and she told me how I would feel and she was exactly right.
I became more ADD than I am. I couldn’t focus. But I was [on] the chemo regimen so I just said, “This is what I have to do.”
Another modern medicine that I just have to be grateful for is anti-nausea because I was so sick [that] I couldn’t stand food. Just looking at it… [On the] third day, [I] was down.
I was lucky because one of Mitch’s brother’s best friends had just gone through the dd-MVAC. He had just had it at MDA and he told me exactly what was going to happen also. “This is how you’re going to feel. Be sure to have some Miralax. You’ve got to have that mouthwash stuff that they’ll mix up for you.”
Margo W.: Did you ever have mouth sores? What was that like?
It was horrible. It was just like my oncologist, Dr. Yorio, told me. He said, “They’re ulcers, Vickie, they’re sores. And if you don’t treat them, you can get infections.”
I did the baking soda salt. Mitch would even mix it up. They add milk of magnesia to it. They pour all this stuff together and you’re supposed to swish it and swallow it because your stomach also has those sores.
Mitch is a great cook. He would fix these meals and I just take one bite and say, “Honey, nuh-uh. I got to have macaroni and cheese if I could even stomach that.”
But my best friend was Mexican Coca-Cola. I don’t even drink Coke but Mexican Coca-Cola was the most soothing drink. I didn’t drink much of it, but it settled my stomach. I felt like I had eaten. It was filling me up. I guess it reacted with those sores because it didn’t hurt to drink it, whereas just water would kill my mouth.
I finished chemo [in] mid-January. I saw my general practitioner in May. He did the blood work [and] he goes, “You know that you’re borderline diabetic.” I said, “Yeah, because I’ve been drinking these Mexican Cokes. I promise I’m getting off of them.” And I did.
I quit cold turkey. I saw them at a store one time and went, “I have to have one.” I’ve got this feeling of I’m going to allow myself to have one. But I got off of them.
Margo W.: Did your hair start to fall out [on] day 14? What was that like? What did it feel like physically? What did you notice and how did you feel emotionally about it?
I had long, long hair and put them in braids one day. We picked the day. I think it was week two. I’d had chemo. I was feeling good because [by] week two, I always felt almost normal.
My daughters came over. They each took a braid. They cut it off. Then one of my daughters styled my hair. Once they cut the braids off and I had short hair, I didn’t notice the hair coming out as much. We did a punk ’do. The girls came over and we just hacked on it. You could see then that I was going bald and so that’s probably 21-28 days.
Finally, I just said, “Mitch, give me your buzzer. I’m buzzing it. I can’t take it. I don’t want to see these hairs on the floor. I don’t want to see them on my body.” I buzzed it, he buzzed it, and then I just started wearing scarves and hats all the time so I don’t have many photos without a hat or a scarf on.
It was challenging because I always did the bun, the braid, and the ball cap. I just tucked it up and off I went and did my thing so it was weird to not have hair.
This is fun now. It’s fun to have short hair. I don’t think I’ll grow it long ever again. I think I’m going to stay with this because I think I’m so different myself that I don’t really want to have that look that I had. I’m from a generation where we grew our hair and never cut it. I’ve had hair down to my rear end, but now, I just go, “Eh, I’m different now.”
Exactly six weeks after my surgery, when I could start exercising again, I was out there doing everything I could to get my physical strength back.
Self-image and cancer
Margo W.: Personally, I had to wrestle with who am I if I’m not a woman with long blonde hair, which sounds shallow, but it’s a part of who we are. Did your sense of identity change? What did you go through when that was happening?
Yes. My identity of being the strongest person in the room like, “I am strong. I can do anything,” was not that anymore. I felt like, “How can I guide anybody?” People come to me for information and guidance and I thought, I guess I’m not that person anymore, but I’m kind of getting it back.
My children and their friends rallied behind me. They come to me and I was freaking out. I thought, How am I going to help these young people if I am so ill?
Exactly six weeks after my surgery, when I could start exercising again, I was out there doing everything I could to get my physical strength back. Just getting older is scary because I don’t have the balance I used to have. I practiced yoga for over 20 years and I had the best balance around and now like, “Oh, I could fall over.”
When people say they fought cancer, that’s great. I don’t think I fought cancer. I wanted it gone. I didn’t want that to be my identity. I wanted it to be more of, “Okay, everybody, I’m here. I’m who I used to be. I may look different,” because I have to tell myself that. I’m not the same.
Live your life now.
Life after cancer
Margo W.: You have [a] presence and I can tell how you’d be an instant leader and encourager of other people. What’s different now? How are you different now after this journey?
I have this little statement in my home office: “Live your life now.” My personality was always, “I’m going to live my life, but I have to get all these other things done.”
I make my bed every morning. I’ve always believed in it. It feels good to me to say, “Okay, I’m actually out of the bed. I’m actually going to make the bed.” I may stay in my jammies in my room for a while and drink my coffee and I go into my day.
I’m a little less “got to get going.” I’ll sit and look outside. I don’t meditate, but I do try to hear those birds singing or the squirrels running around on my roof. I’m going into everything a little less hurried.
I am trying not to be as negative as I used to be. I don’t want to find fault with things. When I catch myself going, “That was not so good,” I’ll go, “Oh well.” And that’s what I say. “Oh well. That’s not important.”
Living intentionally
Margo W.: I think that’s magnificent. You are now living better than you have before because that sounds very intentional to me. Tell me more about how that feels to be able to be in the present. Being intentional and present is hard.
It is, especially for me. I’m just always looking at what’s next, what’s next, what’s next. I still am that person, but I’m not as apt to think that everything has to be in its place.
I used to think I can’t even enter the room unless all this stuff is organized, put away, and everything has to be in its place. So there [are] a couple of things out of place. I’m okay with that.
To me, the word “now” is better than saying I’m in the moment. I’m trying to enjoy being out in the woods. I want to do more hikes. We’re surrounded by great trails here in Austin.
I’ve been trying to ride my bike more. I like volunteering. I was already doing Meals on Wheels, Keep Austin Beautiful, and other little town cleanups. But now it’s, “What else can I do? Where else can I get out of myself and help someone else?”
I still have major anxiety about bad news from a doctor… Now, when I go into these tests, I just have to say I’m going to be accepting.
Follow-up protocol
Margo W.: That’s so cool. Are you cancer-free today?
I’m tested every four months. The first was [at] one month and then the three-month test. The six months is what I’m looking forward to.
Dr. Laviana, every time I get my test results, he’s like, “Oh, I told you. It’s gone, Vickie. We destroyed it. It’s gone.” Talk about an optimist. I hope.
Everybody has that scanxiety. I don’t care at all to look at my calendar and see what the date is. It’s coming up, I just know that.
Dealing with “scanxiety”
Margo W.: The sign in your office says, “Live your life now.” How do you think this experience — getting rid of cancer and all the extreme measures you had to [do] — has changed how you approach every four months [when] you’ve got to go back and find out if you’re still cancer-free or has it?
I don’t think it’s changed. I still have major anxiety about bad news from a doctor.
Everyone that has to go through this, you look at your history and [say], “I made it through that. I made it through this. I made it through that. Wow, I can’t believe I did that.”
I did 10 triathlons. I’ve done all these things and I would have done more but I said 10’s a good number because it does involve a lot of training. That’s a lot of hours in my life training.
Now, when I go into these tests, I just have to say I’m going to be accepting. Obviously, there’s nothing I can do about it. I’m nervous going in. My blood pressure is probably super high.
Then I wait for those results. They come on my phone. I see them. I go, “Okay, Mitch, I’m going to read them right now. I’m just going to go [to] the office to sit down. I don’t want to be in bed reading this stuff.”
I start to read through it and go, “Wow. These are good numbers. It says they don’t see anything new in my lungs and other organs. Whew. I made it through another one.” I look forward to that day. I love hearing from people like you and Dorothy. Just positive that it’s gone.
Margo W.: Surreal experience. It’s an overused term, but it really does apply. As you’re walking around going to doctors and doing chemo, did you ever feel out of body? Like, “Is this happening? I feel like I’m walking in somebody’s physical body, but it’s not really me.”
Every time I get scanned. When they put the iodine in, first, I’m grateful that I can have iodine. I’m like, “Wow, at least I’m not allergic to that.” Then the next thing is, yes, I don’t know where I go, but I do feel like it’s not me, it’s somebody else’s body.
I’m going to come out of here in about an hour, an hour and a half. I’ll get my car and drive away. But each time, especially that scan.
I’m always grateful for science. I say thank you very much so we have the science and the machine that can look for these things.
Being grateful is a coping mechanism for me.
Coping with cancer
Margo W.: I love that you’ve said often throughout our conversation that you’re grateful for things. You’re grateful for science, grateful for medicine, grateful for doctors. Has gratitude always been part of your coping skill?
Yes, I think I’ve always been. I have a temper and I could get angry super fast, but then immediately I go, “Okay, I am grateful because that wasn’t a big truck. That truck almost hit me right as I’m cursing him out.” That’s where I go immediately after something gets my feathers ruffled. Being grateful is a coping mechanism for me.
Words of advice
Margo W.: It seems like you’ve come through a journey that left part of you behind and yet the core part of you is enhanced. What would you share with anybody facing a health challenge like you’ve been through or really any difficulty?
Taking the information that’s given to you. The doctors are giving you information. Hopefully, you’ve got a friend group that’s supporting you.
My sister gave me this wonderful binder. It’s like a baby journal that had pages in little envelopes that you could slide things in, like business cards. I would take that. This helped me through the very beginning. Every once in a while, I’ll pull it out and add something, especially if I meet someone.
I really believe in writing it down. It doesn’t have to be journaling. It’s more of information and who’s helping me.
I realized I had people on a list that I was keeping abreast of what was going on. I did not put it on Facebook. I wanted these people to know that I was doing okay because they were going to hear about it and then I would get information from them. Stay informed.
Everybody has said, “You’re a warrior.” And then, “Oh, by the way, I’m going to drop off cookies,” or “I’m going to do this,” or “What do you need done?” That support is what carried me through even though I’m independent.
My mother, if she were alive, would probably say, “Oh, Vickie let you do that? Wow. She allowed you to?” My mom would have said, “How did you become so reliant on folks?”
Importance of a support system
Margo W.: It sounds like you’re talking about how valuable the connection and the support from your community [is]. It had to look different during COVID. But it sounds to me like you knew, at the time and now still do, the value of that community and support.
If I were sitting with someone that had just been diagnosed, have your friends, family, and connections. I know that’s what church is for. I know that’s what we’ve had in the past in our culture. That’s what’s gotten a lot of people through all these hard times.
Just to have those people, even though they couldn’t see me. [For] anyone that had to go through any kind of health crisis during COVID, it was especially difficult because you couldn’t have those loved ones with you.
Margo W.: Would you say that having a phone call or a FaceTime call with people you care about is as good as seeing them in person?
We have relatives in South America and Mitch’s son lives down in South America with three of the grandkids. They’re like mine. I just am in love with these children. We do WhatsApp with them and so I was already accustomed to doing WhatsApp before COVID.
When COVID hit, it wasn’t the same and I don’t think it can be the same, but thank goodness we have it.
I was imagining all the phone conversations I had with my children. They’re listening to the doctor give us all this news. My girls are listening to everything. Mitch is in the car listening. If we didn’t have that technology and I was by myself in there, jotting notes down, trying to remember everything, how do I tell them this is what I’ve got to process?
It is important to have Zoom and everything. But no, I don’t think it’s anything like having anyone in your house and saying, “Hi, come by for dinner,” or meeting them at a restaurant.
Margo W.: It’s a distant second, but it’s better than nothing.
It is.
Margo W.: What was it like when people wanted to bring you meals? Across multiple cultures, this is one of the things we know to do when things are tough for people. What did that look like during COVID?
That was hard. I really didn’t want anyone to put out. I did not want them to have to cross town. I didn’t want to have them come over, especially since they weren’t getting out anyway.
I would just say, “I’m going to peek out and say hi and hugs to you,” and they would leave it on my porch so we would have social distancing. What a difficult time.
I would accept what I could, but a lot of times, I would say, “Please, please, please, please just take care of yourself. Be safe. I love you. Thank you for thinking of me. When this is all over, we will get together and you can fix me a meal.”
Margo W.: Is there anything else you want to share with people who are dealing with any part of this journey?
You must advocate for your body and for your family. You have to show up and tell them you’re not going to be blown off because that’s what it felt like. It’s a terrible journey.
As you have these tests or whatever they’re recommending, if it doesn’t sound soon enough, I say keep pushing it. Get in there. Go for it.
I remember seeing my general practice physician in February 2020. I went back to him and said, “Why didn’t you do a urine test that day?” He said, “You were in a hurry.” And I said, “I was not in a hurry. You’re a doctor. What are you talking about?” He goes, “No, no, no, I don’t think we did it because you said that you’re in a hurry.” And I was like, “No, I don’t like that answer.” So, of course, he’s not my doctor anymore.
COVID was hitting and I think everybody was afraid to keep you in the office very long because it was right before everything shut down. And that, I realized, was a turning point where I could have stood up for myself and said, “Hey, don’t you do a urine test? Isn’t that part of the physical?” Because that was my physical. That’s why I went in that day.
No matter if you’ve been diagnosed or not, you must advocate for yourself. I remember always thinking, I don’t want to insult the doctor. I can’t tell them what to do. But I do believe you need to stand up for yourself.
Be your own advocate. Don’t let them blow you off.
Margo W.: I think that’s a really good observation. We do have this reverence for doctors [and] rightfully so. They’re in school forever and they know a lot more than we do.But the bottom line is it’s our body. We have one.
I love that you’re advocating for advocating. We need to be willing to be uncomfortable with whether we think we are hurting their feelings or disrespecting them because in your case, advocating for yourself helped save your life.
I don’t have a clue what would have happened if I hadn’t said, “I need to see another doctor. If you’re saying it’s not a UTI, get me the name of that next doctor.”
I really believe in second opinions. If you’re not feeling like this is the right answer, you’re probably right. It’s not the right answer. They’re not giving you the information that you know your body is telling you that something’s the matter.
If I had a class on cancer, that would be one of the first 101. Be your own advocate. Don’t let them blow you off, especially when you’re an old lady.
Margo W.: Regardless of your age. Advocating for ourselves is really key. I don’t think it’s 100% natural for a lot of women for a million reasons.
Thank you so much for sharing your story. It’s heartwarming to hear your story and I’m so glad you’re cancer-free as far as we know right now.
The Right Dose: Finding the Balance in Cancer Treatment
Janice
Janice Cowden is an advisor for The Right Dose. She was first diagnosed with breast cancer in 2011. Nearly five years later, she developed metastatic breast cancer, which meant the cancer had spread to other parts of her body.
Chelsey Pickthorn is also a metastatic breast cancer patient and, together, they discuss advocating for the “right dose.”
Chelsey
Many patients are put on treatments to help lengthen survival but it comes at the cost of severe, debilitating side effects
In this conversation, they voice how to find the right dose, how to bring it up with your doctor, and the importance of advocating for yourself.
I was completely shattered… Being diagnosed at 33, I thought that my whole world had come crumbling down.
Chelsey
Getting the cancer diagnosis
Janice: You actually remember every single moment when you get diagnosed. I can put myself right back in the office, hear the words, and feel the moment.
He said, “I have really bad news. You have stage 4 breast cancer. We have to get a biopsy to see if it’s still triple-negative.” But he just looked at me [and] said, “This isn’t good.” My husband and I both left in tears.
Chelsey: My mom, my grandmother, [and] my great-grandmother on my paternal side all had breast cancer. For me, it was the question of when and how long I have until this [will] happen.
I was suggested to get mammograms at 30 and I neglected to do that. At 32, I found a lump on the left side. I went in and I realized my nipple was inverted. I had a biopsy. They put a clip and everything was fine.
Fast forward one year later, I ended up finding a lump on the right side. Unfortunately, it was triple-negative.
I was completely shattered. I had a business. I had a lot of responsibilities. Being diagnosed at 33, I thought that my whole world had come crumbling down.
Having so many people in my family [diagnosed with breast cancer], I had what I thought was such a wealth of knowledge, but I had never heard of triple-negative.
Breast cancer treatment
Chelsey: I heard the term red devil before and when I heard that, that was when I was like, “Oh, this is really real. This is not just a joke or a simple little thing that might go away quickly.”
I did Adriamycin-Cytoxan and I made a lot of lifestyle changes. Being a hairdresser and standing behind the chair, I had to adjust my work schedule. Touching my legs after a day of work felt like I would shudder at just the tiniest touch, fall to the ground, and be ready for bed.
Janice: I had chemotherapy both times because, at the time, there weren’t any targeted therapies for triple-negative.
When you know you’re metastatic — you’re stage 4, it’s terminal, it’s incurable — I think at that point, you’re willing to endure just about anything because it’s your life.
Janice
Side effects from chemotherapy
Janice: I had a really rough time with my stage 1 treatment, which was Taxotere-Cytoxan. I had horrible mouth sores. I was very, very sick. I ended up having to get two dose reductions during that chemotherapy.
When I had Adriamycin, I didn’t end up requiring any dose reductions, but it made me pretty sick. It’s a really, really harsh chemotherapy. Adriamycin’s known as the red devil and it lives up to its name. It was really tough.
When you know you’re metastatic — you’re stage 4, it’s terminal, it’s incurable — I think at that point, you’re willing to endure just about anything because it’s your life.
Being 33, I wanted to be normal. I really wanted to put on a happy face, pretend I could get through this, and that everything was going to be okay.
Chelsey
Chelsey: The Adriamycin-Cytoxan was nasty. It was just not nice at all.
One side effect [was] peeing red. I’m like, “Okay, this is going through me really quickly.” And you just think, “What else is it hitting that fast?”
I didn’t have so much diarrhea. I had constipation from the steroids and from all the medication and that was the number one thing for me.
After you’re constipated for seven [or] 10 days, you get angry. You just really want it out of you so that was a really big struggle for me.
Being 33, I wanted to be normal. I really wanted to put on a happy face, pretend I could get through this, and that everything was going to be okay. Not being able to really open up and have the support that I needed definitely [affected] my relationships. I had support, but no one really knew exactly what it was like going through it. Feeling very lonely and disconnected from my community [and], at the same time, having them be there. That was really a struggle for me as well.
Janice: When I had the side effects from the Taxotere, I started with mouth sores.
My mouth was so tender. The mouth sores were on my gums, on the insides of my mouth, on the roof of my mouth, on my tongue, [and] in my throat. Anything hurt, even water. It hurt to drink it if it was cold, it hurt to drink it if it was too warm.
Even though I was on a soft food diet, everything burns. It stings and it’s painful. When they start going down your throat, then it’s not only painful when you’re trying to chew food, but it’s painful to swallow. And so you just decide to stop eating and even drinking.
I developed systemic thrush as a result. I went back and forth between all kinds of GI symptoms — diarrhea, constipation — and it would just go back and forth. I lost about 18 pounds in three months because I couldn’t eat.
When you’re dealing with GI side effects, you don’t know what to expect. One day, you may have horrendous diarrhea. Then you may not go at all for another four or five days. And so then you’re really confused. I treat the diarrhea and then I have constipation, then I have to treat the constipation, which then flips back to diarrhea. Your days just center around, Okay, which do I do? Do I treat diarrhea today? Do I take the chance that I don’t treat [it]? Because then I don’t want to get constipated.
When you’re dealing with GI side effects, you don’t know what to expect… I didn’t want to leave the house.
Janice
I didn’t want to leave the house because I didn’t know what to expect. Sometimes those bouts of diarrhea would come on suddenly and you certainly didn’t want to be caught out somewhere, you know? I didn’t feel like going out anyway.
My nose [and] my eyes ran constantly. I was miserable.
Finding out about dose reductions
Janice: I didn’t know about dose reductions. When I went to my oncologist for the third round, I think it was, he saw how sick I was and how awful my mouth and everything else was. I was just in terrible shape. He said, “We’re going to reduce your dose.”
It helped a little bit. But by the time I reached my fourth round, which was three weeks later, I still wasn’t well enough for him to feel comfortable giving me even that dose. So he reduced it [further].
Quality of life and longevity [are] the most important things I’m looking at. Being 38, I want to live as long as possible.
Chelsey
Chelsey: The prognosis of triple-negative and knowing the recurrence rate in five years was very heavy on my mind. Having had two grandmothers who passed away from metastatic disease, I was riddled with a great deal of fear.
At my one year, I noticed a small bump on my upper shoulder and I mentioned it to my doctor. Three months later, it wasn’t gone. It was still there and it was bigger.
I went on vacation and thought, All right, I’m going to enjoy myself on this vacation. But I booked a doctor’s appointment and sure enough, they immediately biopsy it that day.
The next day, I was getting a scan and had the tech basically say to me, “Well, you’re metastatic.” I remember laying there in the scanning machine and just lost it.
If this is what that is, which it sounds like it is, I was like, “Wow, what a terrible way to find out.” I said to my doctor, “I can’t believe the tech would even mutter those words to me.”
Sure enough, it was metastatic and I had another spot on my lung. My oncologist said, “We’ll just put you back on ACT.”
The knowledge that I do have from my mother and my family is many times, chemo is what kills people. I said, “Hell no. I’m not going back on Adriamycin-Cytoxan. There’s absolutely no way because how long am I going to have to live? I’m 34 years old.”
I started trying to put out feelers and figure out what my options were. I had to switch insurances, which was just a huge stress. And, of course, working to have my insurance to be able to then have care was just a terrible situation.
I had foundation medicine done and it opened me up. I have a somatic BRCA mutation so that opened me up to be on a trial for olaparib.
Initially, the side effects were extremely low. I had a couple [of] bouts of diarrhea, but I really tried to control a lot of that stuff with my diet. I basically had been on it for about two and a half years until infections. [In] 2021, I had shingles, impetigo, COVID three times, [and] E. coli twice. The actual personal side effects seemed low, but the infections and the susceptibility that I had to everything [was] just over the moon.
[After being on the olaparib for 1.5 years, she was seeing results]. Once I hit that mark, I said, “Why wouldn’t we titrate or pull things back? Because I’m well and I’m on a trial so it’s very regimented, it’s scheduled.” My doctors were like, “Oh,” at first.
Each appointment I kept going back, “Okay, I’m ready. Are we going to do this?” Finally, I think it had been a year, they went to the trial and requested a dose reduction.
Quality of life and longevity [are] the most important things I’m looking at. Being 38, I want to live as long as possible. I’m not really interested in having leukemia and all of these other comorbidities that develop from medication. So that’s the driving force for me asking for a dose reduction because I was in a place of success, I should say. Why would I continue to keep poisoning myself while it’s done its job at this point?
You have to self-advocate. You have to be okay with going to your oncologist and saying, ‘We need to talk about this,’ because it should be a decision between you and your oncologist.
Janice
Janice: I think a lot of people don’t even realize that they can ask for a dose reduction or they don’t know to go to their oncologist and say, “How can we better manage these side effects I’m having? How can we improve my quality of life? Because I don’t want to give up treatment, but at the same time, I’m not having a quality of life with the side effects that I’m having from the treatment.”
You have to self-advocate. You have to be okay with going to your oncologist and saying, “We need to talk about this,” because it should be a decision between you and your oncologist.
A lot of times, as good as they are at treating our cancer, our physicians don’t necessarily look at the whole person and how our lives are outside of treatment. What is the impact? Are we able to get out of bed during the day? Are we so fatigued? What are those side effects that are causing us to have such a poor quality of life?
The first is just to encourage patients to advocate for themselves. If they are having side effects that are really destroying their quality of life, they need to have that conversation.
Many patients that I’ve talked to [are] afraid to report side effects from their treatment because they’re afraid that their oncologist is going to pull them off treatment that’s working. They don’t want to complain. They don’t want to be seen as a whiner. But these are things that your doctor needs to know.
Clinical trials are quite different than when you’re just getting standard of care from your oncologist because those conversations occur between you and your oncology team whereas, in a clinical trial, you have a few more people that are involved.
But even when you’re in a clinical trial, you absolutely should be able to talk to the trial investigator or the person seeing you, whether it’s a nurse practitioner or just one of the nurses working with you in the trial. You can still report it to your oncologist as well.
These are things they need to know because side effects are reported in clinical trials. For patients who may receive that drug, if it’s FDA-approved down the line, we need to know those side effects. Were they mild? Were they moderate? How much did they impact your quality of life? That’s when we need to determine: is that dose the right dose really for that patient? Because if you reduce the dose and the quality of life improves and the side effects lessen, then we need to look at that a little more closely.
At the end of the day, what we’re looking at is personalized medicine: getting the right dose, the right drug, for the right patient. We don’t experience the same side effects from a drug.
Unfortunately, the new targeted therapies and endocrine therapies come in one dose. What we really need to start looking at is: Are they effective? Are they as effective at lower doses? Does that mean that patients could have a better quality of life and still have [the] quantity of life?
The toxicities would be less because we’re on this for life so you want to preserve as much of your organ function and your general health as you can. When you’re suffering from extreme toxicities and side effects from drugs, sometimes those either cause patients to discontinue treatment or the toxicities become so severe that their organ function is impaired. And that alone will lead to also a lesser length of life as well.
We’ve looked at this whole paradigm of maximum tolerated dose. Decades later, why are we still doing that? Why are we still pushing for the highest dose possible when we could possibly look at the optimal dose?
What is the optimal dose? If that means it’s lower, it’s still effective, and we’re creating fewer toxicities and patients can stay on the drug longer, patients will take the drugs because they’re not dealing with severe side effects, then it’s a win-win. At the end of the day, it’s a win-win for oncologists and for patients.
At the end of the day, what we’re looking at is personalized medicine: getting the right dose, the right drug, for the right patient.
My Dad’s Cancer Journey: How He Inspired Me to Take Control of My Health
Nick has persevered through a series of health challenges. After an agonizing 13 months, he finally got a diagnosis: IgG4-RD, a rare autoimmune disorder. Seven years later, this pseudolymphoma morphed into a rare type of non-Hodgkin’s lymphoma that only represents up to 2% of non-Hodgkin’s lymphomas.
As Nick tries to set an example for his 3 young children, it was the example that his father set for him as he was growing up that taught him how to prioritize his health.
They share the importance of finding a medical team that is a good fit for you, someone you can trust, and why you should always advocate for yourself.
This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Don’t be afraid of the prognosis. Be afraid of not knowing and not doing anything about it. Medicine in today’s world can do a lot of things.
Harry
Introduction
Nick: First and foremost, I want to thank you guys because I wouldn’t be here today. You have supported me through so much.
I feel like because of the way that you raised me, the experiences, the patience, the forgiveness, all of those things [have] helped mold me into who I am today so I just want to say thank you. Thank you for being open to doing this because this is not something that we do typically as a family so it’s pulling us all out of our comfort zone.
Ultimately, it’s not about us. It’s about creating awareness and showing other people of color and just other people in general what this can look like and how important it is to have positive role models in your life. I don’t take that for granted so I just wanted to say thank you for that.
Gail: Oh, you’re more than welcome. We wouldn’t have done it any other way. We wouldn’t have had it any other way.
Nick: A big reason why this came up and why The Patient Story gave us this platform to do this [is] because I mentioned a big reason that I’m still here today is [that] I had you guys as positive role models in my life.
I always saw [you] go to the doctor [and] prioritize your own health so it was just something that was natural for me. As I’ve grown up [and] gotten to meet more people and [heard] what their experiences have been like, that is not the case for everybody and for a lot of people, unfortunately.
What a great opportunity for me to put a spotlight on this and just let people know how impactful and how imperative it is to your overall health, quality of your life, and longevity to prioritize yourself, to go get checked.
Going to the doctor was an inconvenience, but it wasn’t costly and it was for my own benefit.
Harry
What motivated you to prioritize your health?
Nick: What drove you to prioritize your health all of those years, [going] to the doctor and [getting] prostate exams in the middle of the workday?
Harry: That’s how I was raised. My parents didn’t have a lot of money so we used to go to the children’s hospital [in] my early years.
I was raised to go to the doctor and get a physical. Then being in the fire department, you always had to be physically sound.
When I went to Great America, [the] first thing they said was, “Hospitalization. We can get you.” I said, “Well, I got this.” And they said, “No, we’re going to give you ours as well.”
It’s been easy for me because I’ve always worked and always had insurance. Going to the doctor was an inconvenience, but it wasn’t costly and it was for my own benefit. And that’s why we raised you that way.
Just go to the doctor [and] get it checked out. [If] you start coughing, we’ll give you a little cough medicine. If that didn’t work, we’re going to the doctor.
It’s important that everybody gets a checkup. Don’t be afraid of the prognosis. Be afraid of not knowing and not doing anything about it. Medicine in today’s world can do a lot of things.
Good health and peace of mind are the two things that you need the most. Everything else is just like gravy.
Harry
Getting diagnosed with prostate cancer
Nick: You and I haven’t really talked too much about this. I never forget that you had cancer, but our experiences were vastly different.
You went all those years and got these exams. Did anything ever come up? Any signs or symptoms along the way?
Harry: It really was a shock to me, to be honest. I go to the doctor annually. If I got sick, I go to the doctor. I worked for that and the insurance is there so I would go.
I went for a routine [check and the] urology doctor says, “Something ain’t right.” They did a biopsy and he said, “You have prostate cancer.” So I said, “Well, what do we do?” And he said, “Well, you can live with it or we can take it out.” And I said, “Take it out.”
People make such a big deal of things that aren’t necessary to have a happy life. Good health and peace of mind are the two things that you need the most. Everything else is just like gravy on potatoes is what it is.
Nick: I love that.
Harry: That’s the gravy of life. So I got a little less gravy, but I still got life. It wasn’t a hard decision. It wasn’t an easy one, but I did what I thought was the right thing to do.
Nick: It’s so powerful to have both of you [as] examples [and] also you as a strong black man, prioritizing your health, and not letting whatever stigma or what other people think. That is why you’re still here with us and I’m extremely grateful for that.
You had surgery. They removed the prostate and I’m sure that that was extremely challenging as well. Can you share a little bit about that experience?
I was raised that God [doesn’t] give you burdens you can’t carry. So I just carry it, not worry about it.
Harry
Harry: The hardest part is when you get the diagnosis. When I prayed about it and thought about it, it wasn’t that big of a deal. I’m still here. I’m still living. I still have fun. Still got my wonderful wife.
It didn’t change my life. It didn’t make it worse. It didn’t make it better. It’s just something that happened. I was raised that God [doesn’t] give you burdens you can’t carry. So I just carry it, not worry about it. Wake up every day, happy to be alive. Got my faculties about myself. It’s a great day.
Gail: Because he acted so quickly and was going to the doctor, it had not gotten to the prostate wall.
They did not have to do radiation so that was great. Now we go every three to six months, depending on what his urologist says, and just [have] the PSA checked. We’ve got that coming up.
I don’t go to [the] doctor every time I get a cough or a sneeze, but I do get regular checkups. If they find something, we do what we can about it.
Harry
Dealing with “scanxiety”
Nick: One of the things that cancer survivors often continue to combat is test anxiety or scan anxiety.
Nick: You got to go quarterly and for some people, that’s a lot. It has them relive all of these things that were pretty traumatic.
I have developed different things in my own routine to handle that. Do you ever have any scan or test anxiety? Do you ever worry?
Harry: No, no. They say you need to come [to] get checked, I go get checked. That’s all I can do.
I’m not a doctor. I don’t know medicine so I can’t judge. If he says I need to be checked, I do it. It’s that simple.
[For] a lot of people, it’s denial. They don’t want to be sick so they try to deny it, put it off, or push it back. I’m not that guy.
I don’t go to [the] doctor every time I get a cough or a sneeze, but I do get regular checkups. If they find something, we do what we can about it.
Nick: This is what I do as well in between appointments and before I go in. We talk about managing our expectations, objective thinking, neutral thinking, [and] just telling yourself the facts.
The facts are I feel good. I have everything I need to win the day. I’m loved, I’m provided for, I’m safe, and, right now, to my knowledge, I don’t have cancer. No one’s told me that so I’m going to move and operate as if I don’t have cancer. If that comes up again, then we’ll deal with it when that happens.
But often, that scan anxiety and test anxiety can just manifest. Honestly, I feel like sometimes that can lead you back into a resurgence of cancer because you’re living in a state of toxic stress and anxiety.
Gail: The negativity.
Nick: As I continue to learn more about this, when you’re in a state of toxic stress and worrying about things that you can’t necessarily control, your immune system’s down and you create an environment for disease to come back up.
A lot of the stuff that just fills me up and that has helped me get through the trials of my own life.
You are rooted in everything that I do — the way I move, the way that I think, my tattoos — all of it. I’m extremely grateful and I love that it comes from you guys.
When you do find somebody, you stick with them because then you develop that rapport, that trust.
Nick
Understanding medical mistrust
Nick: I don’t want to assume or generalize, but as I think about medical mistrust and the fear of going to the doctor, from my understanding [and] knowledge of history, black people haven’t always been treated the best in the medical community. We were the subject of test experiments for years and that just doesn’t go away. What can be done? Where is that mistrust rooted?
Harry: I recall the segregationist when I was growing up. But my father always wanted us to have the best, so he fed us and took us to the doctor to make sure we were healthy.
You just have to put your trust in the doctor that you have. When I came back from the military, my mother’s doctor [became] my primary care physician. After a while, he told me, “I got a new guy coming on. You guys could grow up together,” and he’s still my doctor to this day.
We had a great relationship. I tell him, “Just tell me like it is. Tell me what it is and what you recommend.” I put my faith in him.
Nick: That’s the only doctor I know you’ve ever seen.
Harry: Yeah. He’s good. My mother always made sure we got a physical every year. If we got a cold or cough, my dad would try to treat us with his remedies. My mom said, “I’m taking him to the doctor.” That’s how I was raised so I don’t have a problem with doctors.
Gail: I think, too, that you do have to just trust.
I’ve said many times: every doctor is not a fit for everybody, but you shop until you find somebody who is a fit for you and then you put your trust in that particular doctor. If you don’t trust them, then move on and find somebody else.
For the most part, doctors are in that field for the right reasons. You have to trust that they’re going to do the best [for] you. I don’t care if you’re red, white, black, green, or yellow. You have to put your faith in the doctors and in God. God will take care.
Every doctor is not a fit for everybody, but you shop until you find somebody who is a fit for you and then you put your trust in that particular doctor.
Gail
Nick: That’s great. I love that because that is the same thing that you taught me about advocating for myself as well. If you don’t feel comfortable with a certain doctor or you don’t like the way the visit went, that doesn’t mean that you have to stay with that doctor.
[It’s] the same thing with therapists. Just because I didn’t have the best experience with this therapist in this city [at] this time on this date doesn’t mean all therapists are bad. It doesn’t mean all therapists don’t get me. It doesn’t mean that therapy doesn’t work.
It just means that I need to continue to advocate for myself and continue to look. Then when you do find somebody, you stick with them because then you develop that rapport, that trust.
From autoimmune disease to non-Hodgkin’s lymphoma
Nick: I think that was in July 2013 when I first got sick and went to the hospital. They told me my heart was enlarged, my prostate was enlarged, and I needed to go to the cardiologist right away [and] cease physical activity and sports. Everything right after that kind of picked up.
It wasn’t immediate but that triggered a domino effect of going to the doctor almost every month. I was getting sick with different things.
Autoimmune diseases impact everyone differently in different ways and can sometimes be tricky to diagnose. But one of the things that I think you guys will both remember — and I know you could definitely have empathy for — was that discouragement of going to so many different appointments, getting surgery to remove lymph nodes, bone marrow biopsies, and then not having conclusive results, not having a diagnosis. It would have been easy to kind of cash it in.
I told Shelby at one point, “You shouldn’t be going through this. Nobody deserves to go through this. I don’t want you sitting in doctor’s appointments. We’re kids.”
But nobody gave up. Even when I had lost my steam sometimes, my support system — you guys and Shelby — always motivated me to continue to go. [You even] drove me if I didn’t want to go.
Nobody had given me anything to make me believe that they were going to be able to cure me or help me figure this out.
Nick
That was a learning experience in itself. Having the procedures done [at the Mayo Clinic], the full body plasma transfusion, another bone marrow biopsy, and then them sitting us down like, “Hey, we’re going to do surgery on your heart,” and then talking to us about the statistics and risks and having to sign papers.
Nobody had given me anything to make me believe that they were going to be able to cure me or help me figure this out. I remember almost bargaining with God and just like, “If you get me out of this, if I can at least make it through this heart surgery, I will change how I’m living. I will try to get better.”
I was fatigued. I was drained. I didn’t have the mental capacity. I didn’t have the physical energy to be able to ask good questions. I didn’t even know what to ask. I didn’t know what this looked like, what you’re supposed to do, or how you’re supposed to go about this.
You don’t get a handbook that says, “Here’s how you should go about this. These are the question you should ask,” so having someone like you who is anal about that kind of stuff was a game changer. I’m sitting there, embarrassed, I’m like, “Ask one more question, please. Can we just go?” But that is what you do need. [Having] you doing that is huge.
Gail: They treated you with chemo.
Nick: But I wasn’t a cancer patient, so I didn’t fit into a support group. I had you guys, but I didn’t have the resources of being in a cancer support group, even though I was being treated and talked to as a cancer patient, and being told I had lymphoma, which was difficult.
Then now [I] have a type of non-Hodgkin’s lymphoma that only represents up to 2% of non-Hodgkin’s lymphomas. I’ve been [an] interesting case before. I’m already a case study at the Mayo Clinic. I already understood that I was like hitting the lottery. Now I happen to be his only patient that had the IgG4 mutate into a full-blown lymphoma, also [a] rare type of lymphoma.
But I trusted him and I trusted Dr. Islas. Even though I got the understanding of stage 3-4, I never thought was going to die. I knew because I had done so much work investing in myself: getting sober, going to therapy, and working on myself emotionally, mentally, spiritually, [and] physically. It was almost like I personally believe my higher power got me ready to go to war to be able to face this.
Keep good notes and ask good questions. It’s your health. Advocate for yourself.
Nick
Words of advice
Nick: Keep good notes and ask good questions. It’s your health. Advocate for yourself.
Gail: Be diligent. With [the] insurance system, you had to keep going back and forth with them. I think that’s why some people give up and don’t want to fight. You have to be diligent about it. You have to keep in touch with the insurance companies.
At one point, when they told you that insurance wasn’t going to pay for the Rituxan, you could have easily just said, “Okay, well,” but you didn’t. You fought with it and your doctors because you trusted in the doctors.
You stayed on it. You stayed on it and your doctor stayed on it so that you were able to get help.
You can’t give up. I tell the little guys all the time, “We’re Mundys. We don’t give up.”
Harry: We don’t quit.
Nick: Yeah, Mundys don’t quit. But you’re absolutely right.
If I’m being completely honest, another reason why I went a full year without it was [that] I was defeated. I was so pissed off. I felt like a victim. It’s like, “How do I, the patient who is going through hell, have to sit and be the middleman between the insurance company and the big hospital when the hospital made a mistake [in] billing for an injection?”
They coded it as an injection because that’s the standard of care that most people were getting. I was only approved to get it intravenously so when they billed me for an injection, which was not what I received, I got stuck with a $20,000 bill. The insurance people are like, “Well, you got to pay this,” and I’m like, “I’m not paying this.”
I had done that for years before because it had happened multiple times. At that point, in the middle of COVID and all, I was being naive, too. I’m like, “I’m good. I don’t want to deal with this.” But once again, my doctor stayed [with] me.
That is why I have been able to accomplish what I’ve been able to accomplish. That’s why I’m where I am today. I know that you guys are definitely proud.
I hope that you guys are here and I hope I’m here long enough to continue to see the fruits of your labor and all of the stuff that you have continued to just invest in me and see other people benefit. It’s extremely profound when you think about it. I’m just extremely grateful for it.
Harry: You’re a good man. I love you. You really are. I’m very proud. You’ve been through a lot and you kept your head up. Never heard you complain. I’m thrilled to be sitting here with you today. I don’t want to get emotional so I’m going to stop.
Gail: We love you and [are] very proud of you. We just want to see Mundy Mindset continue on with the next generation.
Nick: We got three great ambassadors in the making.
That is why I have been able to accomplish what I’ve been able to accomplish. That’s why I’m where I am today.
Nick
Marginal Zone Lymphoma Patient Stories
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In 2019, she was diagnosed with stage 2 breast cancer, which metastasized to her lymph nodes.
In this story, she shares how she developed a second cancer, the challenges she underwent with her treatment plan and how she continues to “thrive” as a survivor.
This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Name: Renée F.
Diagnosis:
Breast Cancer
Staging: 2
Initial Symptoms:
Breast shaped differently
Dimple in breast
Flat nipple
Treatment:
Maintenance Treatment:
Whatever stage you are in and whatever year in your journey you are in, may I remind you: you’re still here. You are still thriving. Even if it was a hard day yesterday, you’re here and that is to be celebrated and enjoyed.
It really took hearing my daughter say, ‘My mommy is a cancer survivor,’ to understand that when we say it, it’s power. We’re getting our power back by saying, ‘I have cancer.’
Life after leukemia
I’m a single mom. I’ve been on my own since she was born and it’s been really tough. But at the same time, I have her looking up at me. It’s like, “How do I explain to my five-year-old (at the time) that I have cancer? How do I reassure her and myself that things are going to be okay?”
I remember being afraid to say the word cancer because it’ll make it real. Then I realized I need to call it by its name because it needs to know my name. If I give it space, then I have some ownership over that, have some control, and it eliminates the scary a little bit.
It really took hearing my daughter say, “My mommy is a cancer survivor,” to understand that when we say it, it’s power. We’re getting our power back by saying, “I have cancer,” and so is saying, “I’m sick.”
To miraculously get pregnant just blasted all of my doctors’ minds because they’ve always said this is medically impossible. It’s clinically impossible. Total body radiation for two months. There was no fertility at all.
It’s even more incredible because I had my bone marrow transplant [on] September 17, 2002. Eleven years later, I miraculously got pregnant. My due date for my daughter was September 17, 2013. She arrived early [though].
When did you start to notice something?
When I got diagnosed with breast cancer, it was like a sucker punch, but at the same time, I kind of knew what to do this time.
For the last 20 years, we’ve been monitoring my blood work, focusing on my immune system, my anemia, and kind of touch and go on other things. There’s been lumps and bumps throughout the years, but everything has been biopsied and perfectly fine.
I was doing a regular monthly check and didn’t feel anything different or strange. I was about to get in the shower but I dropped something. When I went to pick it up, I saw my reflection in the mirror and noticed that one of my boobs was shaped [differently] when I leaned over. I thought, That’s strange.
I grabbed another mirror and did a couple of little movements then realized if I put my arm up, this whole breast was a totally different shape. I thought, That’s different, so I noted it.
The following day, [as] I’m getting dressed, I notice there’s a weird dimple in my boob that wasn’t there before. Maybe I gained weight. I weighed myself. A couple of days go by and now [I] notice my nipple is flat but I don’t feel anything. It just looks different on the outside.
I had a routine follow-up appointment with my doctor, the one who told me I was pregnant, and [as] we’re finishing things up, she tells me, “Is there anything else before we leave today?” I walk out and said, “Oh, I forgot to tell you! My boob looks kind of weird.” She goes, “What?” She took a look at it and immediately sent me over to get a mammogram.
When we got to the appointment and my doctor walked in, she didn’t have to say anything. She just started crying.
In the middle of getting the mammogram, the nurse left the room, came back, and said, “All right, you need to get dressed. We need to go to a different room because we need to do a biopsy.” I was like, “What? Right now?” She’s like, “Yeah, right now.”
She took me to another room, set me up for a biopsy, did this whole biopsy, called the doctor, and then told me, “I’m going to leave you here because I need to go take your results to the lab. Your doctor wants it stat.”
I’m laying with my arm up on this table for what feels like forever. She comes back, does two more biopsies, marks me up, and then says, “You have an appointment tomorrow with your doctor. You should bring somebody with you.”
My mom came with me. When we got to the appointment and my doctor walked in, she didn’t have to say anything. She just started crying. I was crying and said, “What is it?” She goes, “It’s metastatic breast cancer. It’s stage 2.” I said, “How come I didn’t feel anything?” And she says, “It’s behind the breast tissue. It’s along your rib cage and it goes all the way to the back.”
It was a whirlwind [of] scheduling and trying to figure out what we do now.
Cancer genetic testing as a bone marrow transplant recipient
I had to contact all of my bone marrow transplant doctors and let them know what was going on because it meant that we had to do completely different genetic testing. I’ve had a bone marrow transplant so it was a whole different ball game for me.
When you have a bone marrow transplant, it wipes out your immune system [and] also your blood system. When you have an organ transplant, you have a donor organ being transplanted into your body. Bone marrow is an organ so even though I’m me on the outside, technically, I am my sister.
Because of genetic testing, we’re able to determine whether or not this is a line that carries in our family history and if we need to be concerned for other members [of] the family. When you have somebody else’s bone marrow, I’m technically her makeup even though I have my own genetic makeup.
It sent the scientists on a whirlwind trying to figure out what tests to do on somebody like me where if we do a blood test, it’ll show my sister and what her predisposition conditions could possibly be, not mine.
Luckily, we were able to determine that this breast cancer was not genetically inherited. It was in direct relation to, most likely, the chemical burns, doxorubicin, and total body radiation, which is weirdly comforting in the sense that at least I know it’s not genetic.
It’s a little frustrating to know that this is from what I had to have. If I would have known then what I know now, would I change anything? No, not at all. If I would have known then that I would end up at 35 years old with stage 2 breast cancer, I still would do everything the same.
Treatment
What was the treatment plan?
The plan was to go with chemotherapy and radiation to wipe out the immune system and bone marrow to do a full bone marrow transplant and cross our fingers. The long-term routine was to continually check the blood levels and make sure that everybody is where they’re supposed to be.
Then just managing the chronic issues from the treatments — fibromyalgia, migraines, and things like that — and regular cancer awareness routines, self-checks, and making sure to get my first mammogram at 40, and just stick to that.
When I got diagnosed with breast cancer, it changed everything because I had so much chemotherapy given to me in 2002. There’s only so much your body can have maximum. I’m on eight doses out of ten.
What was really frustrating was that once we found out that it was metastatic breast cancer, I already had a lot of the typical chemotherapy that’s used to treat this type of cancer.
It would be in my best interest to do a different chemotherapy routine, hope that that works, and shelf the remaining doses of doxorubicin, just in case, and just try our luck.
If I would have known then that I would end up at 35 years old with stage 2 breast cancer, I still would do everything the same.
How did you process this diagnosis compared to your first?
I think I processed this one better because I was awake. When I was going through leukemia, I was so sick, medicated, and comatose so I really don’t remember a lot.
I’m thankful because we kept daily logs of what was going on and I can look back. Thank goodness I don’t remember because I don’t want to.
Walking into treatment brought back flashbacks that I was not expecting to have and moments that I was not prepared to cope with. I think it made it hard for my family to embrace the situation because I did keep a lot of things internally.
You have these emotional breaks where you’re just a wreck and people don’t know how to cope with that. They don’t know how to comfort somebody. “Oh, you’re going to get better. You’re going to be fine.” Not really helping.
Tell me I can be angry. Tell me it’s okay to be upset. Then tell me I’m strong. I got through yesterday. Remind me of another time when it was really tough and I got through that. Because no matter how hard this might be, even if I’m on the floor in the fetal position, feeling desperate and clinging to life, I’m still clinging to life and that is to be celebrated, that is to be focused on.
Tell me I can be angry. Tell me it’s okay to be upset. Then tell me I’m strong… No matter how hard this might be, even if I’m on the floor in the fetal position, feeling desperate and clinging to life, I’m still clinging to life and that is to be celebrated.
Breaking the news to my daughter
Having my five-year-old and facing the biggest fear that I had being a parent — what do I do if this comes back? — I had to embrace it as best as I could and explain it to my kid without terrifying her.
I was teaching preschool and told her, “When you make artwork and you add glue, paint, and glitter to things, sometimes it gets really messy. You can’t go over and erase glue and glitter. Sometimes, you have to just start over. If you look at people, we’re made of glue and glitter. Sometimes things get a little messy and that’s why there [are] doctors. They come in, erase the board, and clean it up so that you have a new space to create something new. And that’s basically what mom’s going through.”
I had a unilateral mastectomy so it means that I had just one breast removed, mostly because we needed to hurry up and get started on treatment.
Side effects from treatment
Hugging my daughter was different. It changed. Those were things that I wasn’t really expecting to deal with.
Hair loss? I knew that was coming so I wasn’t going to sit around and wait for my hair to fall out. I started cutting it and then we shaved my head.
My daughter and I got henna tattoos. I got one on my head and continued to get henna tattoos because, from my previous experience, wigs were not comfortable for me. I didn’t like the feeling and it was hard to wear my masks.
What did you learn from going through leukemia that helped you?
As far as being prepared and using some of what I have learned from leukemia to help me with breast cancer, it was the hair, the food train, and financial resources. But the emotional stuff, I was not prepared for.
It took me a long time to realize that a lot of the things that I was doing in [the] clinic were from [my experience with] leukemia, like instantly asking for a warm blanket. That solidifies that I’m really here. This is really happening. I know my way around. This warm blanket brings me some comfort because I know what to ask for. In the cafeteria, I also know to ask for vanilla ice cream instead of applesauce.
Sometimes you need to have a moment with nature to remember [that] you’re just this small little stardust in this great, huge world. There’s surviving and thriving all around you.
What helped you process your breast cancer diagnosis?
Mindfulness practice is huge. I didn’t realize how. I’m an Aquarius so I love water and anything related to water, but I didn’t realize how much that impacts your emotional wellness and stabilizes some of these things.
When I was going through leukemia, I would listen to [the] sounds of the ocean. I’m locked in this room. I can’t leave. I’m bedridden.
My mom would fill the basin with ice-cold water, rocks, and shells that I had from my collection, and she’d swoosh it back and forth for me. I just closed my eyes, put my hands in the basin, feel the waves, trance out, and go where it doesn’t matter.
It’s still something I practice. It’s still something that I hold on to. I have a fountain in my yard. I love the rain because it’s just so beautiful.
I went surfing for the first time and in an instant of wiping out and bleeding in the ocean, I realized my cancer doesn’t matter. Cancer doesn’t matter [at] this moment. If a shark really wanted to eat me, he’d eat me. He doesn’t care if I have cancer.
Sometimes you need to have a moment with nature to remember [that] you’re just this small little stardust in this great, huge world. There’s surviving and thriving all around you.
The moment that I realized that there is peace [in] being in nature was the moment that I realized that I see hearts in clouds. I see hearts in leaves. I see hearts in rocks. I see hearts constantly in nature. I feel like it’s some type of validation or affirmation. You’re part of this, too. Keep growing. Keep being in this moment.
When you’re submersed in nature and captivated [by] the mystical beauty of it, you start to forget your problems and then you start to breathe. It feels so invigorating, [like] that feeling after a good workout.
What happened after you got a unilateral mastectomy?
Due to the timing, with my history and everything, we had to do surgery right away to eliminate the problem as much as we could physically and then attack it with medicine. We rushed in and did a unilateral mastectomy and removed the entire left breast and my lymph nodes on the left arm.
As soon as I recovered from that, I started chemotherapy again. I was on Taxotere and Cytoxan. I had to do home injections as well so it was paired with chemotherapy. That was for about six months.
I had six rounds total of chemo then I had targeted radiation to the chest and parts of my arm. I had about 25 sessions of radiation and then started the process of healing.
In 2020, we did a scan to check everything. There [were] markers in the right breast, but the findings weren’t as aggressive as what we discovered in the left breast. When we did that scan, it revealed that I actually now would also need my thyroid removed. There [were] tumors there as well. It was just safer to remove the entire thyroid and not leave parts of it.
I had chemo and radiation again, a ton of surgery, only to find out that we were going to go take something else. And that was in the middle of the pandemic, too, so it was terrifying.
They removed the thyroid. I’ve had no problem since then and I’ve been on this long-term hormone, anti-cancer regimen for the last couple of years and I’m on it for a few more years. I think I get off in 2024.
[In] April [2022], I was finally stable enough, health-wise, to have a finalized mastectomy and DIEP flap reconstructive surgery. Because of all my radiation and how much they had to remove from the chest wall, implants were not an option for me.
DIEP flap surgery is grafting different parts of either your back or your abdomen to make boobies. They were able to graft my abdomen, move it all up, and do a full reconstructive surgery.
The right side gave me a ton of problems and I’ve had a bunch of complications since then — necrosis and staph infections. I’m still bandaged [after eight months], but I’m getting there. I’m almost done healing and I have a normal-ish-looking body again. I don’t have to wear a prosthetic breast anymore, which was a whole lane to walk down, too.
At this point, things are stagnant and that’s a good thing. My health is stable. The treatments are working. My blood looks great. Still anemic like usual, but everybody’s acting right.
I don’t consider myself cancer-free. I consider myself a survivor but more than anything, I consider myself a thriver.
How do you feel knowing that everything is good and stable?
To be honest, mixed feelings because it’s this basket of hope, like, “Yehey! I get to get on with my life again, move on, figure out what life is like with my stomach is my boobs now, and rebuild [and] re-plan my goals.”
But on the other side, it’s, “All right. Is this the calm before the storm? What’s next? If we’ve removed parts that I can function life without, what do you come for next?”
I don’t consider myself cancer-free. I consider myself a survivor but more than anything, I consider myself a thriver and that’s where I associate myself with my health and [the] long term.
Words of advice
Don’t stop dreaming. I know it sounds so cliché. Make that vision board. If you focus on living in all ways, then you remove the stress, fear, and worry.
I have plenty of days where [I’m] down and mopey and all I can do is sit on the couch. But I know that there will be a day [when] I have energy and I’m out there, living, touching, tasting different things, and feeling the world. It’s okay to have both days.
Just because you’ve been diagnosed with cancer doesn’t mean it’s over. It’s not over yet. You’re not dead yet. When it gets too much and nature doesn’t work or listening to music doesn’t work or talking to somebody doesn’t work, my best advice is [to] go clean something.
Organize something. Accomplish a small, achievable task. You can polish it up. You can reorganize it. You will take pride in that. Then all of a sudden, dopamine and serotonin and all these things start running through you because you achieved.
Whatever stage you are in and whatever year in your journey you are in, may I remind you: you’re still here. You are still thriving. Even if it was a hard day yesterday, you’re here and that is to be celebrated and enjoyed.
I have never been good with body image and loving myself the way that I look and who I am in my skin until I got breast cancer. Then I started really, really loving the fact that I heal really [well] from things that try to destroy me.
When I get caught up and it really takes a toll on my emotions or my finances, I have to remember how much I heal. I have to touch my scars and remind myself: we rebuilt. Sometimes you need to touch your scars to remind yourself that you’re still here and you’re a freaking badass.
If you focus on living in all ways, then you remove the stress, fear, and worry.
Renée was 18 when she started noticing bruises but she was on the cheerleading and dance teams so she just associated the bruising with those. After she had her wisdom teeth removed, her health rapidly declined, prompting her mom to bring her to the hospital. She shares her story of how her cancer journey began.
Renée was 18 when she started noticing bruises all over her body. At first, she thought the bruising was normal because she was a cheerleader and dancer.
After she had her wisdom teeth removed, her health rapidly declined, prompting her mom to bring her to the hospital.
She shares her story of finding out she had an aggressive type of cancer, being told she won’t be able to have kids, and the miraculous surprise of finding out she was pregnant.
This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Name: Renée F.
Diagnosis:
Acute myeloid leukemia (AML)
Initial Symptoms:
Bruising
Treatment:
Chemotherapy
Radiation
Allogeneic bone marrow transplant
All I was holding on to was trying to keep it together because these little, itty bitty pediatric kids are looking up to me.
‘We don’t know what’s going on just yet, but because you’re 18, we need to ask you if you have a DNR.’ I panicked… and immediately signed my rights to my parents. Then the rest was a big blur.
Introduction
I’m from California. I love the ocean. I love hiking. I’m very artistic and creative, and I like to find careers that allow me to utilize that creativity. I was a preschool teacher for many, many years.
I’m a single mom. I’m kind of obsessed with my kid. My world revolves around her. [It’s] really special that I get to relive all my favorite things from my childhood with my daughter.
She is incredible and very smart. She’s got an old heart, an old soul, and she’s determined to be a doctor or a surgeon so we’re working on that. And we have two cats.
I can’t control how this disease ended up in me, but I can control what I’m going to do now.
Pre-diagnosis
What were your first symptoms?
I was a senior in high school. I was a cheerleader and a dancer so I was covered in bruises all the time and always achy. That was normal for cheerleading.
I got my wisdom teeth pulled. Surgery [went] perfectly fine but after, things went downhill really, really fast.
My mom, who insisted that there was something wrong, rushed me to the hospital. They did some blood work and told us, “Don’t go very far. You’re not being admitted yet, but we’re going to get the results fairly soon so just stay close by.”
[After] maybe 20 minutes, the hospital staff was running down the hallway with the wheelchair, yelling my name. They found me and my mom and said, “You need to come with us. We need to take you back to do more testing, but we need to get you back to the hospital.”
They brought me in and said, “We don’t know what’s going on just yet, but because you’re 18, we need to ask you if you have a DNR.” I said, “I don’t have my driver’s license yet.” She said, “That’s not what that means,” and explained to me what a DNR was.
Because I was 18 and really sick, I had two options: (1) sign off my rights to my parents, be completely admitted to the hospital with unknown circumstances, and let my family make decisions and choices on my behalf because I was going downhill very quickly; or (2) make my own decisions and sign a DNR.
I panicked, didn’t really know how to respond to that, and immediately signed my rights to my parents. Then the rest was a big blur.
They told me that I had a less than 25% chance of making it through the night, let alone the week… I hadn’t even gotten my driver’s license or my high school diploma yet and everything was just ripped away.
Everything quickly went downhill
I was diagnosed [on] May 27, 2002. I had my wisdom teeth pulled prior to my diagnosis. It went downhill really quickly.
I’m trying to think back: when did I first really notice symptoms? When I was 16, I broke my fibula. I had a spiral fracture. Could it have been from then? I don’t know.
I don’t know how I ended up with this. I went to a very small Catholic school in Fremont. [Out of] 32 kids in my elementary school class, four classmates including myself were diagnosed with a form of cancer — two with breast cancer, two with leukemia, and two required bone marrow transplants. I was number 2. All before we were 35.
It makes your head spin and at the same time, you get nowhere. I can’t control how this disease ended up in me, but I can control what I’m going to do now.
In my mind, there was no other option. It was going to work, I’ll be damned.
Diagnosis
From that moment on, I spent about seven months in the hospital. I was in [the] ICU, hanging to life. All my friends from high school were called. All the teachers. Everybody just took off and flooded the hospital.
At the time of my diagnosis, they told me that I had a less than 25% chance of making it through the night, let alone the week. I was going to need two platelet transfusions and two blood transfusions right then and there just to get me stabilized.
If I made it through the week, there was a 50% chance the treatments would work [and] if they did, there would be a 50% chance of developing [a] secondary cancer. The treatments would cause me to be infertile because there is not enough time or science to consider any fertility-saving options.
I hadn’t even gotten my driver’s license or my high school diploma yet and everything was just ripped away.
I’m a very religious person so it was a very religiously-powered, emotional roller coaster. I clung to my faith, used music as therapy, and practiced mindset mindfulness.
How did you process the diagnosis as an 18-year-old?
Lucky for me, I’m very stubborn. Being the third out of four girls, you got that middle child syndrome so you want to be heard, you want to be seen.
At that time, I was at a really low point in my life. My parents had gone through a really bad divorce and it was just really hitting me hard. When you’re a teenager, struggling with your emotional wellness and where you fit in this big, crazy world, that’s a lot to carry on your shoulders. Then add to it something that you have no control over, that’s fully taking over your life, and you just scream for control.
In my mind, there was no other option. It was going to work, I’ll be damned. It’s going to work. That was just the mindset.
I remember telling people, “I can’t have you crying in front of me right now because I’m going to lose it. If you cry, that’s fine. Just do it outside. I need to stay stable as best as I can.”
I’m a very religious person so it was a very religiously-powered, emotional roller coaster. I clung to my faith, used music as therapy, and practiced mindset mindfulness, things I didn’t even know I was doing then that are so fundamental now.
The hardest part was that because I was 18, I was the oldest kid in pediatric oncology. When other kids came by my room, they saw my cheerleading graduation pictures [and] the artwork that my friends left, and they came to me for advice.
I remember hearing one of them say as she was leaving my room, “Daddy, I didn’t know cheerleaders could get leukemia. I thought just kids got it.” Hearing that and not knowing where the hell I’m going to end up was just gut-wrenching. I have no other option. I’m not done yet.
My oncologist, who’s still friends with me today, [would] come over every morning. “Are you still fighting with me? I’m fighting for you. Are you still fighting with me?” And I would tell him, “Yeah, absolutely.”
Every time there was news that this treatment didn’t work or that we had to try this other chemo because it was stronger, my answer was always, “Whatever you have to do.”
When I think back to when I was going through this, I wish I heard more stories to hold on to because all I was holding on to was trying to keep it together because these little, itty bitty pediatric kids are looking up to me.
My oncologist [would] come over every morning. “Are you still fighting with me? I’m fighting for you.
When did you get your diagnosis?
It was the same day that I went to the hospital for that blood test. This sweet old man came over and was talking to me and my mom. He says, “She has acute myelogenous leukemia.”
My mom said, “No, she doesn’t. You have the wrong test results. Her sister just got over mono. She has mono.” He said, “No, it’s not mono. It’s really serious. And if we don’t treat it right now, she’s not going to make it.” I asked him, “I’m not going to make it to what?” And he goes, “To the end of the week.”
I can honestly say it took years for this to set in, that this is what’s going on. The only way I could process it to make sense was that it was like a really, really bad sinus infection and that’s it.
Anybody that I had ever known who had cancer died. Kids don’t die from this. You’re not supposed to. I’m supposed to go do things. I was really involved in youth group and cheerleading. I had plans after high school to volunteer. I was going to work at the camp and go build more houses in Mexico.
I remember asking my doctor, “Okay, so in a couple of months, when this is done, I can go to Mexico, right?” And he goes, “Sure.” I think he knew right then and there how to counter the fact that I had problems comprehending what was going on.
‘If we don’t treat it right now, she’s not going to make it.’ I asked him, ‘I’m not going to make it to what?’ He goes, ‘To the end of the week.’
Treatment
I remember that first blood transfusion, that first bone marrow biopsy, and [the] spinal tap. I remember being in bed, machines going berserk, and telling my mom I couldn’t breathe. Then waking up months later, seeing my reflection in the hospital window of this bald person.
[I] had a patch over my eye because I had an infection. I had an infection from my port. I had an infection from my PICC line. Tubes everywhere. I was completely bedridden.
It was really late at night. I woke up and kept leaning over. My mom says, “What are you doing?” I said, “Who is that person staring at me?” And she goes, “Where?” And I said, “Right there. There’s this weird person staring at me.” And she goes, “Honey, that’s you.” She hit my morphine pump and I fell asleep.
I woke up and my friends and my sisters had made [a] list of all the famous bald people in the world and they put my name at the top of the list. Then they all started dyeing their hair purple.
It just swept over me. I was engulfed in this environment.
Because it was 2002, it was very hush-hush, especially after the recovery. There was nobody to talk to.
The therapist would come by and would be like, “You look really upset today. Is there something bothering you?” And I’m like, “Hmm. Hmm. It’s raining.” I would be so sarcastic. I went to sarcasm to cope because it was so extreme.
What was your treatment plan?
They started me on chemotherapy immediately. I had a PICC line put into my chest and was started on a seven-day treatment.
By day six, the chemotherapy had burnt a hole through the PICC line and caused this massive staph infection. My whole boob swelled and it was just awful. They had to rush me into surgery, remove the PICC line, put it in my arm, and continued with the chemotherapy.
After the chemo was finished, we found out that the chemo did nothing but piss off the cancer. The infection spread. Now I had an infection [in] my eye and things were just going downhill.
They put a PICC line in my neck. By that time, I was in intensive care. They started me on stronger chemotherapy. I believe it was doxorubicin because that’s what basically wiped it out.
I was completely comatose and had about four or five IV poles.
They had to move it. They put it [in the chest area] and it stayed stable for a year. But I had all these other infections now that picked up staph and it was just a mess. By [that] time, they had finally figured out the right chemotherapy to combat the leukemia.
Acute myeloid leukemia is a really fast-growing, aggressive cancer. They blasted me with doxorubicin, sent me over to Lucile Packard Children’s Hospital in Palo Alto, and blasted me with even more chemotherapy. I think the last round was a week’s worth of chemotherapy in 24 hours. It was insane.
I had mucositis. I threw up my esophageal lining. It was a mess.
‘You can’t start my radiation until you crank up Smack My Bitch Up by Prodigy. I need this to get through this,’ and they did. They totally obliged. You got to do what you got to do.
Radiation
They had me do total body radiation. They had to tape me in this photo booth-looking thing because I had to stand up but I was really weak.
They would zap me then I’d come back later and they would do the back. I had to do it three times a day — front, back, front — and then the next day would be back, front, back. It was like that for a week. I had to do a separate lower-dose radiation treatment just on the lungs.
Bone marrow transplant
After, it was basically wiping out my immune system. I was completely immunocompromised. I was in double-door isolation for months. I couldn’t have visitors. I couldn’t see my friends.
All of my friends are off in college, living their dream, and I’m in prison, in the hospital. I graduated high school in [the] intensive care unit on speakerphone. My sisters accepted my diploma for me.
Most of the time in the hospital, I was clinging to life, bedridden, and in critical care. I was diagnosed in May. By September of that year, I had finally been prepared with chemotherapy and total body radiation to have a bone marrow transplant from my sister.
I have three sisters and lucky for me, two of them matched me perfectly, which is incredible because I’m mixed race. I’m Mexican and Italian so if they didn’t match, it would have been a nightmare.
My bone marrow transplant was the easiest thing out of everything. My doctor carried it in the bag and gave it to me. It was still warm and it was this mushy, orange-ish-looking, goopy, slimy thing in a bag. They hooked it up to my IV.
My sister was in recovery for a couple of hours. I ate cheese puffs and watched Monsters, Inc. for the millionth time. [I had] a lot of Benadryl and morphine.
The day after the infusion, they did [a] bone marrow biopsy to see how much of my sister’s had come in. From day one, it was good to go and immediately multiplied. From that point on, it was just monitoring to make sure that I developed a little bit of graft versus host but not enough to cross the threshold of safety.
I learned how to flush my own lines, mostly because I begged them to not make me come in every single day, twice a day, to flush my lines.
I was allowed to leave but because I was still so fragile, I had to be within one mile of the hospital for any situation. I stayed at the Ronald McDonald House in Palo Alto.
I had IV pumps that I had to continue doing. I learned how to flush my own lines, mostly because I begged them to not make me come in every single day, twice a day, to flush my lines. I told them, “I’m 18. Can you just teach me? I’m off [the] hospital campus. You can teach me.” They taught me how to do it.
I stayed at the Ronald McDonald House for about three months, came home for my 19th birthday, and started to rebuild my life from there.
I was immunocompromised and neutropenic for about a year so I was in complete isolation.
I have a sensitive immune system. It was 2002 so not a lot of people really understood that. I lost a lot of jobs because my health was so fragile and it made me look like I wasn’t a consistent employee.
Remission
When they tested my bone marrow [on] day two or three, it had shown 85% [of] my sister and no percentage of me so as far as acute myeloid leukemia is concerned, I was in remission.
The chances of developing AML a second time were there but not any more of a concern than developing [a] secondary cancer.
They told me from the very beginning that the treatment that I [had] to have does cause other cancers and that because of my ethnicity, I’m already on the cusp of some other health issues, like heart disease and diabetes.
The protocol was to continue monitoring me as if I still actively had cancer. They outlined a five-year regimen. I had to get all of my vaccinations again [within] a certain time frame.
I had a lot of radiation done to my body. I had serious wounds and scar tissue. Radiation, scar tissue, and cancer just love to group up so there was concern of tumors, but [they didn’t] want to do mammograms [at] 22 so it was just ultrasounds and regular checks.
We’ve been monitoring my blood work every 3 to 6 months for the last 20 years. I have chronic anemia and my immune system is not my age. I’m 38. My immune system is only 20 years old so that meant going back to work was really difficult because anywhere I worked, I instantly got sick.
I [was] already [burdened by] chronic issues from leukemia, but now I have a sensitive immune system. It was 2002 so not a lot of people really understood that. I lost a lot of jobs because my health was so fragile and it made me look like I wasn’t a consistent employee.
The ripple effects are still felt emotionally, physically, and financially. Honestly, I didn’t start to cope and deal with my leukemia until I got breast cancer. I packed it away. I didn’t know where to go to cope with it.
If anybody asked me about the scars, I would make up stories… I didn’t want to be deemed the ‘cancer girl.’ Nobody falls in love with [a] girl with cancer is how I always saw it in my head.
Fertility
The effect of cancer treatment on fertility
In the back of my mind was this huge, unspoken conversation about fertility. I want to be a mom. I obsessively asked, “Do you know what my chances are after I recover from this stuff? If I’ll be able to get pregnant?”
I asked everybody to the point where they were like, “Renée, you need to just let this go.” It was like that for 11 years. I researched what tests we could do. I did everything possible. For 11 years, the answers were always, “There’s nothing. It’s not happening.”
From the time I was diagnosed, they told me that the treatment will cause infertility. I remember asking them right away, “How do we save my fertility?” They told me flat out, “We don’t have enough time to do what we need to do to save your fertility options.” And in 2002, they really didn’t have the science backing it too much either.
They had to prepare me for the worst because they really didn’t know either and I respect that. It was hard to process. Being told at 18 that you’re not going to be able to have kids then finally being able to recover and be free, you go a little crazy. You’re like, “Screw the world! I’m going to love everybody then and mask my pain with that.”
I went from being this pure, Catholic-raised, Christian girl where I’m told to respect my body, that my body is a temple, and nobody is to touch it or violate it to wide open, everybody touching me, everybody feeling things, everybody looking, taking pictures, cutting me open, putting in this, putting in that, and it was like, “What happened to this temple that I was?” It was really hard to rebound from that and to have all these scars associated with it, too.
[I was] obsessively asking and trying to find out, “If I eat more berries, will that increase my fertility? If I do this pose, will that help?” Trying whatever I could.
Then I got into a relationship where we were both really equal in if we have kids, that’s great [and] if we don’t, it’s no big deal. We were together for a long time.
After going through [treatment], my body went into medical menopause. I was taking hormones so I could get my period. It had been 10 years since my transplant. The doctors wanted to do a full panel test on me so they could scan everything and see what was going on. They wanted me off all of my hormone control medications.
I go to my doctor… She’s doing the ultrasound… She had me sit up to see and she goes, “Renée, you’re pregnant.”
Getting pregnant against all odds
I was off my medications for one year and got pregnant. Didn’t know. Started feeling some symptoms.
I go to my doctor, [who] has been my doctor for 15 years. She knows me very well. She’s doing the ultrasound and she’s already having the conversation with me. “Okay, Renée, if it’s a tumor, it’s going to probably look kind of clustered and it’s going to look like… Oh.” And I said, “Kind of like O? Like it’s going to be like an O shape?” And she goes, “No, look!”
She turns the monitor and grabbed my leg and said, “Did you see that?” I said, “Yeah, what is it?” And she goes, “It’s a baby!” And I said, “Whose?” And she goes, “Yours!” And I said, “How?” She’s like, “Well, you know how, but you’re pregnant!” And I was like, “No, I’m not. I can’t be.”
She had me sit up to see and she goes, “Renée, you’re pregnant.” I’m like, “No… You’re sure?” She’s looking at it and goes, “Oh my goodness.” I said, “What?” She goes, “You’re 14 weeks! You’re having a baby in six months!” “What?! What?!”
It was the most confusing day of my life. I had to call all of my doctors. I called Lucile Packard. All of them were like, “Wait. What?” As soon as it settled in, they all said, “We can’t wait to see our baby.” Everybody said Ava was theirs.
That became this quest of, “What am I getting myself into? What is my health? How does my health impact this baby? Is she going to have any side effects because of what I’ve been through?” It was really interesting to be able to go down that door and get in that space of all these different conversations.
It had been so much time since my treatments that if anything, she’ll be really small, probably premature, and [have a] low birth weight. But other than that, everything else looked perfectly fine.
The beautiful part was that during my pregnancy, all of my chronic symptoms — fibromyalgia, migraines, light sensitivity, and eye issues — disappeared. I had a beautiful pregnancy. It was easy. I ate ice cream every day. It was lovely.
We found out that she was stuck in my pelvis upside down so I had to have a C-section to get her out. I went into labor two and a half weeks early. I had a planned C-section that was now moved forward. But that went perfectly fine. She was small but healthy and has been growing like a vine ever since.
It was a full-circle moment. I knew that if I wanted to be a mom, I could go and adopt but I wanted to feel [being pregnant]. I remember bargaining with God. “I’ll do anything. Anything. You just let me feel it one time,” and I got lucky.
She was small but healthy and has been growing like a vine ever since. It was a full-circle moment.
Words of advice
Hold on with an iron grip. I believe in manifestation. I believe that our universe is listening to us. If you think it, believe it, pray it, hold on to it, eat and breathe it, and obsess about it in a positive way, you’d be surprised at [the] results. It might not be exactly the way that you planned it, but it’ll be close.
We all came from stardust so to be where we are right now took a lot of work by forces that know you better than you know [yourself].
Does it hurt? Does it suck? Yeah. But sometimes, when things don’t work out the way that you plan them, it’s because it wasn’t your plan. Understanding that is powerful. Knowing there will be a time [when] you will look back and remember when you prayed for the things that you have.
Hold on. Keep asking questions.
When things don’t work out the way that you plan them, it’s because it wasn’t your plan and understanding that is powerful.
Hearing other patients’ stories
After I got through leukemia, my oncologist came over and told me that he had another patient that was about my age that had just been diagnosed. She was really upset and [asked if] I could go talk to her and share my story. And I did.
It went from one patient to another [and] another to [it] becoming a routine. When my oncologist met new patients that were struggling with accepting what’s going on, he called me to come over. I’d come to the hospital, sit there, collect their hair with them and put it in the basin, share my story, and show my scars.
I wish I had people that were older that came to my bedside and told me their stories. For me, it was an eight-year-old little girl and she’s still my soul sister to this day.
We need to eliminate the shame of sharing our personal health issues and that we shouldn’t talk about this. It is private, but it’s also very emotionally deep. If we don’t talk about this kind of stuff, it will [have a] ripple effect and impact the rest of our lives.
When we talk about it, it kind of clears those clouds so that that little sliver of light gets in. It’s all you need. Just a little sliver of light.
We go through difficult things in life but to hear that somebody else went through it is comforting… When we talk about it, it kind of clears those clouds so that that little sliver of light gets in. It’s all you need. Just a little sliver of light.
Renée went into remission after going through chemotherapy, full-body radiation, and a bone marrow transplant. For the next 20 years, she’s monitored closely. After a regular breast self-exam, she noticed that one of her breasts was shaped differently. A mammogram and a biopsy reveals she has stage 2 breast cancer.
Newly Diagnosed Multiple Myeloma Highlights from ASH 2022
What Newly Diagnosed Patients and Caregivers Need to Know
Multiple myeloma patient advocate Cindy Chmielewski has been living with myeloma for nearly 15 years. After experiencing excruciating back pain for two years, she was diagnosed with IgG Kappa stage 3 multiple myeloma.
In this conversation, she speaks with Dr. Caitlin Costello a hematologist-oncologist at the University of California, San Diego and Dr. Sagar Lonial, the chief medical officer at the Winship Cancer Institute at Emory University.
They discuss cutting-edge treatments and therapies for both transplant-eligible and transplant-ineligible patients, combination therapies and the necessity of stem cell transplants.
Thank you to Janssen for its support of our patient education program! The Patient Story retains full editorial control over all content.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Cindy Chmielewski, Myeloma Patient: I’ve been living with multiple myeloma since 2008. I was a fifth-grade teacher and I simply loved my job.
Around 2006, it became very difficult to teach. I was experiencing excruciating back pain. Standing was very hard, recess duty was almost impossible, and I couldn’t even take my class on a field trip. The tears would come down my cheeks. That’s how much pain I was in.
For the next two years, I was prescribed pain medication and physical therapy. I was a very different person than I am now. I grew up in [the] age of doctor knows best so I really didn’t question what my doctor was doing, although I thought that maybe we should be taking an X-ray of my back.
I was diagnosed with IgG kappa stage 3 multiple myeloma. The multiple myeloma was in over 99% of my bone marrow.
I started treatment immediately. The treatments back in 2008 were very different than now. In the beginning, I had a tough time. The treatments were not touching my myeloma. I had initial success, but then it stopped working. I had a stem cell transplant and that didn’t work. I was devastated. I really didn’t think I was going to live much longer.
A treatment that my doctor suggested began working for me. It worked so well that it put my disease into remission.
Since about 2010, I’ve been on maintenance therapy and able to live my life. In the meantime, I retired from teaching because I didn’t know what I was going to be doing.
I’m a different person now. I don’t teach fifth graders; I teach myeloma patients about myeloma and how important it is to be actively involved in your care, not to be that person like I was back in 2008 just blindly following doctor’s orders
It’s important to learn all you can about your myeloma, to ask questions, and to make decisions. It’s so exciting because now, there are so many treatments to choose from that if one thing stops working, there are so many other choices.
[In this conversation] I talk with two myeloma specialists about the latest happenings for the newly diagnosed population coming out [of] a meeting called ASH [American Society of Hematology].
Dr. Caitlin Costello is the hematologist-oncologist at the University of California, San Diego who specializes in treating multiple myeloma and participates in many of the myeloma clinical trials.
Dr. Sagar Lonial is the chief medical officer at the Winship Cancer Institute at Emory University, the chair of the hematology and medical oncology department, and a lead voice in the myeloma research community.
Transplant-eligible and transplant-ineligible patients
Cindy, TPS: Usually, newly diagnosed [patients] are broken up into two groups: transplant eligible and transplant ineligible. Before we even start talking about what’s happening in that area, how are those defined? How do you know if I’m transplant-eligible or ineligible?
Dr. Caitlin Costello: Good question and, actually, a bit of a moving target. [Transplant eligibility] is usually assigned at the time of diagnosis. A patient first gets diagnosed with multiple myeloma.
Historically, oncologists got kind of a gut instinct to say, “This patient is younger, older, healthier, less healthy, [have] a good performance status.” They’re independent [in] their activities of daily living. They can bathe themselves. They live alone. They do their own grocery shopping. Whatever it is. We’d look at a patient and say, “Healthy, not healthy, old, young,” and make generic assignments to people.
That’s really challenging to do when someone’s first diagnosed with myeloma because when you’re first diagnosed, you’re sick. You don’t feel good. You’ve spent months trying to figure out what’s going on. It may have taken a while to get the diagnosis at that point. Many bones have been affected by myeloma. It can be very painful. A lot of people just aren’t what we think normal health is.
Traditionally, we have made assignments when patients were first diagnosed to say, “You are healthy enough, strong enough, or well enough that you can get an intensive regimen called a bone marrow transplant or not.”
There’s been a bit of an evolution to the concept of transplant eligibility as some more data has emerged to say, “Does everyone have to get a transplant?” Maybe we don’t need to use those same kinds of assignments to make that determination.
I think the better way to distinguish between patients who may be able to get a transplant and patients who may not is frailty. Frailty is a little bit more of an objective, as opposed to a subjective, means of evaluating someone’s health and independence.
[It can] really help identify those patients who may be candidates for more intensive therapy throughout their myeloma diagnosis and their treatment. That is kind of where we’ve landed on transplant eligibility and ineligibility. Do we think people are well enough to undergo a bone marrow transplant?
Improving frailty in patients
Cindy, TPS: Frailty is dynamic now. It can’t be just measured at one point because, throughout the course of treatment, you may improve because the treatment is helping you out.
Dr. Costello: That’s our goal. So many patients are not well when they’re first diagnosed but can turn around pretty quickly where they perk up. Their bone pain is under control [as well as] their anemia, their kidney disease, or whatever way the disease manifested.
Treatments now are so good that patients are responding so quickly. They get better quickly. The way that your doctor first met you when you were diagnosed is unlikely the same person that they will meet two months down the road after you’ve started treatment.
Our job is to continually reassess your health and your general wellness to make that decision because what you were yesterday may not be what you are tomorrow.
Treatment for transplant-ineligible patients
Cindy, TPS: Let’s talk about that group, transplant-ineligible patients, people who may be not strong enough for their body to endure this treatment. What’s the most common type of treatment that this group of people usually get?
Dr. Costello: A bit of an evolution as well. We’ve had so many new drugs developed in multiple myeloma. When drugs get developed, they are first approved for patients who have had many prior treatments. They’re looking for the next newest and greatest.
That’s usually how the FDA approves these drugs. They approve it and say, “Let’s just start with this group of patients.” Over the years, it gets tested with more and more patients earlier on in their diagnosis.
One of the things that patients with newly diagnosed myeloma, who are not planning or not eligible or too frail to go to transplant, have enjoyed is the addition of daratumumab to the first treatment you receive when you’re diagnosed.
Daratumumab, [as] I like to describe [it], is a bit of a magnet. It’s technically called a monoclonal antibody, but it is a medicine that predominantly is given as a shot. It is particularly looking for a sign on the myeloma cells that says, “Hey, this is me.” When it finds it, like a magnet, it sticks to it.
That helps pop it open and it pops it open with many different approaches. It’s a real kind of targeted treatment and uses your immune system to help kill as well. I have seen daratumumab evolve into the gift that keeps on giving because it really has helped so many patients [at] various time points in their disease.
Now, being so effective, why wait? Why can’t we use it when patients are first diagnosed? That has really now turned into the optimal treatment as a basis for when older, frail, weak, or less healthy people are diagnosed with myeloma.
But remember, we like to use multiple drugs. I think of it as like the old game of Clue. Instead of just using a candlestick, a revolver, or a lead pipe, we want to use all the tools we have together as a cocktail so that we can approach the myeloma, sneak up on it, and kill it [in] different ways.
Daratumumab is great in combination with many different treatments. I’d say the frontrunner right now is the combination of daratumumab with lenalidomide, also known as Revlimid, plus or minus dexamethasone, which is something that we’ll get into.
What is maintenance therapy?
Cindy, TPS: Since this is a program for newly diagnosed patients, sometimes all these terms are hard to understand. Can we talk about what maintenance therapy is? Why is it important?
Dr. Sagar Lonial: That’s an important question and it gets into another important data set that was presented at ASH [2022], really focusing on [the] duration of maintenance therapy. What we know is that if you give highly effective therapy, you will get a deep response.
Many of the measures we use to evaluate how much myeloma remains are not perfect. Even MRD, which is minimal residual disease testing at one in a million or fewer, is still not necessarily a surrogate for [the] cure or elimination of the disease.
What we’ve learned is that a little bit of low-dose, non-intensive therapy can maintain that remission for a longer period of time. In randomized trials [where] patients that got no maintenance therapy versus patients that got Revlimid alone as maintenance therapy, the remission duration was at least double for the patients that got maintenance therapy.
The goals of maintenance therapy are to be low intensity and not necessarily impact [the] quality of life. While I’m aggressive about continuing maintenance as long as I can, I usually say we continue until progression or toxicity. Obviously, toxicity is an important variable in that discussion.
What we now know is that high-risk myeloma patients need more than just Revlimid as maintenance therapy. Our group, and now several other groups, have shown that a drug like Velcade added to Revlimid, or carfilzomib added to Revlimid, is able to induce deeper and more durable responses, particularly in high-risk patients. Maintenance means lower intensity, but the goal is to ultimately improve outcomes.
3 vs 2 drugs (MAIA trial)
Cindy, TPS: There were some updates in the MAIA trial at ASH [2022]. Can you tell us the latest and greatest from the MAIA trial?
Dr. Costello: The MAIA trial was designed for [the] patients that we’re talking about. They got the combination of three medicines — daratumumab, lenalidomide, and dexamethasone — and compared it to patients in that same group and only gave them two of the medicines — lenalidomide and dexamethasone.
The whole point was to understand: is three better than two? If so, how can daratumumab help improve above and beyond just the two? It was designed for patients when they were first diagnosed, not going to transplant. [They] use these treatments for as long as they are effective and as long as it’s tolerated by the patient.
It’s been a good number of years now since this trial started [and] ended. [They] are still following these patients for many years to try and see over time not only how successful it is but how durable it is.
The greatest thing and probably the most important thing we can do is [to] get people into remission the first go around. We like to say the first cut is the deepest. How can we have the most success when the myeloma is in its most kind of naive state? It doesn’t know any better. It’s not going to become resistant. We want to throw our best kind of weapons at it first.
[In] the MAIA trial, over the last many years, we’ve seen updates that come out that tell us time and time again that the three medicines combined are [an] extremely successful combination to get people into remission [and] keep them there.
The durability is because we are killing so much myeloma. The myeloma you can see above the surface [and] under the surface that’s very hard to detect. We’re just killing it all.
By making the myeloma stay away, people are living longer. We’re seeing all these outcomes and results from the MAIA trial year after year, showing that the success of these three medicines together is great because it works and it lasts.
Using 4 vs. 3 drugs for treating transplant-eligible patients
Cindy, TPS: The MAIA trial was trying to see for the ineligible patients if three is better than two. For the transplant-eligible patients, I know the question is, “Is four better than three? Should we be adding daratumumab to RVd (Revlimid, Velcade, dexamethasone)?” One thing that keeps coming up is quality of life. Can we talk about 4 vs. 3 in the newly diagnosed transplant-eligible population?
Dr. Costello: If we’ve proved three is better than two medicines together, it brings up the next natural question: is four better? That question is trying to answer if [they should be] adding daratumumab to another group of patients who have just been diagnosed with myeloma.
Let’s say that this is a younger, stronger, healthier group of people, who we have historically treated with three medicines called lenalidomide, bortezomib, and dexamethasone. For the last many years, that combination has been the mainstay. It’s been the most widely accepted, most successful treatment that we’ve been able to achieve ever. But we need to always do better.
The GRIFFIN study looked at patients who were younger, healthier, stronger, going to go to transplant, divided it in half, and said, “I’m going to give you three medicines like we always do. This is the current standard of care,” or, “I’m going to give this other half four medicines.” The same treatments that the first three got — Revlimid, Velcade, dex — and add the daratumumab to it for a group of four.
All patients got the treatment that they were assigned. All patients subsequently had a bone marrow transplant. After the transplant, all patients got consolidation and maintenance, which just means a little extra therapy after your transplant, followed by some amount of maintenance therapy, which is usually either fewer drugs or lower doses as a means of maintaining the successes you’ve had from all the treatments prior.
By comparing four drugs to three drugs for this group, again, daratumumab keeps winning. We see that daratumumab is effective at deepening response, killing more myeloma, making it get into remission more likely, [and] allowing patients to get back to themselves, to get stronger, and to continue on some amount of medicine that’s going to allow the myeloma to stay in remission in very deep ways.
Again, seeing the same outcomes we saw in MAIA, the addition of daratumumab to our standard of care allows for great successes that last.
Do you think the 4-drug combination will be the new standard of care?
Cindy, TPS: Do you think the four-drug combination is going to be the new standard of care for newly diagnosed myeloma patients?
Dr. Costello: I don’t think “will.” I’m already doing it. It’s hard to ignore the data when it’s that good. Granted, the reason I think why you’re asking is because the trial that was done was technically a phase 2 trial, where [there is] a lot of drug development and new combinations.
The people that are the most critical of statistics and evaluating successes are the ones that really want to see what we call big studies, phase 3 trials, randomized data, or you’re comparing the standard to something new and novel. Those are happening. The same drugs, the same study, more patients — it’s happening. We’ll get that information.
But on the same token, if I already have some information that shows me just how effective it is with a good number of people, I don’t want to wait. I want to do good and do well [for] these patients with these early successes that we’re seeing now. I think it’s here.
Who is eligible for quad-based therapy?
Cindy, TPS: When you’re talking about quads upfront, are we talking about all patients? How about frail, transplant-ineligible patients?
Dr. Lonial: I think it typically tends to be the transplant-eligible [patients]. If somebody is frail enough that transplant is not really an option for them, I’m a little concerned about whether you can really give them a quad.
There are some trials that are testing that right now and I’d like to see some of that data. In general, for the truly frail patient, the dara-len-dex (daratumumab, lenalidomide, and dexamethasone) combination is so good. Median remission is five years. It works regardless of age. That was evaluated in the MAIA trial.
I think that that’s a pretty good regimen and I’d like to see whether adding in bortezomib to make it four drugs really does improve not just death but [the] duration of response or lets us discontinue therapy at a certain point, which would be a huge step forward for that patient population.
Cindy, TPS: We’re talking about dara-len-dex upfront for the frail as opposed to RVd upfront. Is there a role for RVd now? Should it be a quad or dara-len-dex?
Dr. Lonial: I think there is a role for RVd in the frail patient, with weekly bortezomib in a patient that may have [a] high-risk disease. I still do believe that the proteasome inhibitor adds benefit there.
I don’t think carfilzomib is necessarily the right drug [for] a frail patient. I am still using RVd, in the beginning likely without dara, but certainly willing to add it in if I need to, if we don’t get where we want to go.
What does it mean to be high-risk?
Cindy, TPS: What do you mean by high risk?
Dr. Lonial: There are both clinical and laboratory features of high-risk myeloma that I think people should be aware of.
An elevated LDH, lactate dehydrogenase, is one evidence of that. Circulating plasma cells [are] another laboratory evidence of extramedullary disease. Genetics, meaning FISH (fluorescence in situ hybridization) testing, looking for certain high-risk genetics on the myeloma cells. Things like 17p deletion, where you’re missing p53, 4;14 translocation, 14;16 translocation. In general, those are considered high-risk features.
On the clinical side, patients that present with a lot of myeloma outside of the bone marrow, extramedullary disease if you will, tends to be high-risk disease as well. Some of these characteristics you can identify on lab tests. Some of them you can identify on exams or imaging. Those are the general rules that we use to try and evaluate risk at the time of diagnosis.
Side effects for different drug combinations
Cindy, TPS: The other thing that patients always are concerned about are side effects. Are there more side effects with the four drugs than [with] the three? What about quality of life? What are you seeing in your clinic?
Dr. Costello: The addition of daratumumab to any of these regimens, fortunately, is a reasonably well-tolerated medication. It is initially a little bit more inconvenient because of the frequency of the dosing.
This drug is given once a week for eight weeks then every two weeks for another eight times. After those first six months, it goes down to once a month, which is a very attractive option for patients. They can just come in once a month, get their blood drawn, get a shot, and get out of there. From a perspective on [the] quality of life from inconvenience, I think it’s a really nice option.
The greater side effect we think about — there’s probably two, I would say — that we’ve learned a lot in the midst of a COVID era.
One is [a] very small risk: 1 out of 10 patients with the first injection may have what we call an injection-related reaction, where patients may, kind of like a bee sting, have a variety of reactions.
Like a bee sting, you may get a little red spot, but some other people may need to have an EpiPen. With your first dose, we have to kind of stare at you a little bit [to] make sure that you’re not having those reactions. After that first administration, the likelihood of having a reaction is somewhere about 1 to 2% thereafter, so very low. The reaction risk is small but important.
The second one — and I think it’s a little bit more relevant these COVID-era days — is that multiple myeloma patients inherently have a weakened immune system. Their immune system is so busy making myeloma that it’s not making adequate amounts of your normal immunity.
If you take a drug that’s designed to kill the immune system problem, you’re going to take some innocent bystanders with it. The daratumumab is going to try and kill all those myeloma cells, but those myeloma cells are plasma cells. Plasma cells are designed to make the weapons you need to kill the bad guys, whatever it is — flu, COVID, pneumonia, whatever.
If we are taking patients who already have a somewhat weakened immune system or [are] trying to get their immune system to build back up, there is going to be some effect on the immune system that puts patients more at risk for getting infections.
It’s important to make sure we are prepared for that. Vaccinating against the handful of different things we know are important for myeloma patients, whether it’s COVID, flu, or pneumonia, and sometimes using preventative antibiotics when patients are first diagnosed.
I’m glad to say that unlike other medications that we use with myeloma that cause neuropathy where you have numbness, diarrhea, or severe fatigue — things that really can affect your day-to-day lifestyle — I don’t think daratumumab affects it as much.
The necessity of stem cell transplant (DETERMINATION trial)
Cindy, TPS: We have all these wonderful drugs that you’ve been talking about now. In the era of these novel therapies, is stem cell transplant still needed initially?
Dr. Costello: The million-dollar question. It’s ironic because it keeps getting asked. I think everyone is so hopeful that we can get rid of auto transplants because we have all these new medicines. Every time a new medicine comes out, the question is posed. A trial is done to say, “Do we still need [a] transplant or is this better?”
That’s what this trial was designed to do. It took patients who were eligible for transplant, divided them in half, and gave everybody the same medicine: our triplet combination of Revlimid, Velcade, and dex.
[Then they] said, “You get this and you go to transplant. You get this and you don’t go to transplant. Let’s see what happens between those two,” with the idea of looking at [if] one group [is] going to have their myeloma come back sooner than the other group.
The DETERMINATION study was the U.S. version of it. The French had their own version and they’re always ahead of the game with us with clinical trials. They were able to complete enrollment, get the results, [and] publish it well before we did.
They showed that patients who got [a] transplant stayed in remission longer than those who didn’t. But after looking at the data for a handful of years, what they saw was that there was no difference in how long people lived.
[There are] lots of arguments about whether that is important — and one would argue yes — [and] whether enough time had passed by to say, “Here we are. We keep applauding and patting ourselves on the back for how well these treatments are working. Maybe we haven’t had the full time pass by, enough to say that there’s going to be a great difference in survival or not.”
When the Americans did theirs, the only subtle minor difference was that after [the] transplant, patients stayed on Revlimid maintenance indefinitely, as long as the maintenance was working.
If they did not go [for a] transplant, they stayed on Revlimid as long as it was working, which was different from the French. They only took it for 12 months and then stopped.
There were a good number of people who stopped therapy and often never had progression for 6 [to] 7 years. What the American side of the trial showed was similar. The transplant group stayed in remission longer.
The survival was no different, but there did seem to be improved time to staying in remission because, we think, of the longer-lasting use of the maintenance Revlimid.
I think it begs the question: is it that we need to get rid of transplant or is it that transplant is complementary? They parsed through that data left, right, up, and down to try and understand: was it the blondes who did better, was it the African Americans who did better, or [did] someone who had different kidney function do better?
[They] tried really to see: is it a general statement we can make across the board? I think the thing that was the most helpful for me to try and parse through whether or not transplant was important or still has a role… While I would love to know that it saves lives, let me hearken back to my “the first cut is the deepest” comment.
If we are really trying to make a deep impact in myeloma when it’s first diagnosed with the presumption that that’s going to allow for the longest periods of remission until the next newest and greatest comes out, then it’s pretty clear the way they parse the data to say that those who had transplant are more likely to get to what we call MRD negativity, minimal residual disease, which is [myeloma] way under the surface.
We have lots of tricks to count myeloma. I can do a bone marrow biopsy instead of my pathologists. They look under the microscope and say, “Yep, I see it. Nope, I don’t.” But in 2023, shouldn’t we have super high-tech technology that can look for myeloma in the smallest little micron of DNA?
Dr. Costello: We want to try and get rid of every last bit of myeloma because those patients, we can tell time and time again now, are the ones who are staying in remission the longest.
The DETERMINATION study was helpful for me to say we’re not saving lives. We’re not letting people, as far as we know, live longer because of doing a transplant, but we are having patients stay in remission by doing it.
Maybe we need more time to pass by, maybe we don’t. I think for the meantime, transplant really seems to me — disclaimer, I’m a transplant-er — that it’s complementary. I think it works with our novel agents, not better or worse than our novel agents.
Dr. Costello: Maybe we can try and figure out if our initial treatments didn’t do the job, maybe that’s the group of people who should proceed. So stay tuned. Lots to come.
Dr. Lonial: I think that with the results of the DETERMINATION study, it’s pretty clear to me that even with good drugs, transplant continues to offer [a] benefit.
There are a lot of folks that say, “Well, if you’re already MRD-negative [and] it’s cycle 4, maybe you don’t need the transplant.” We actually don’t have any data that says that. My goal is to maximize the duration of that first remission because the myeloma is never more sensitive than it is at the time of the first presentation.
By the time it relapses once or twice, you may lose the ability to gain the benefit from high-dose therapy, really high-dose melphalan. Certainly, at our center, we encourage patients to go into transplant in the first remission.
IVIG and daratumumab
Cindy, TPS: What about the use of IVIG with dara? Is that being used at all?
Dr. Costello: It is. I call [IVIG] a magic trick to try and build your immunity up a bit. Whether your myeloma is not making enough of an immune system or the treatments have compromised your immune system, your IgG, which is one of your weapons to kill the bad guys, can be decreased, can be accidentally killed, [or] can [be] whatever to suppress your immune system.
If your immune system is weak because your IgG levels are low, why don’t I just give you some IgG? That’s what IVIG is: intravenous immunoglobulin. If I can give you some booster to your immune system, perhaps that will prevent some of these infections from happening.
Historically, the way IVIG has been approached is to say if someone has severe, recurrent, life-threatening infections, those patients should receive IVIG. As we’re getting more and more aware of some of these infections that can happen with a variety of different medications that are out there for multiple myeloma, I know I have become much more liberal with my IVIG use because I think it could only potentially help.
Dexamethasone
Cindy, TPS: Let’s talk about this other drug that’s been around forever. As a matter of fact, I think in ancient times it was the only drug used to treat myeloma: dexamethasone. It’s always part of every combination.
Some studies being presented show that in the frail population, after a couple [of] rounds of therapy, we can maybe start lowering or dropping dex. Can you talk a little bit about that, too?
Dr. Lonial: In my experience and those of many of my colleagues, when we use dex, particularly in older, frailer patients, we tend to use a lower dose and for a shorter duration of time.
In my mind, the maximum benefit of dexamethasone is the first four to six months. I will often start to taper after the first or second cycle to try and get to lower doses and then hope to be off between month 6 and month 12.
That approach is something that many of us are doing in general. [For] patients getting daratumumab, for instance, the label says dex before and after the dose. We only have to do that for the first two cycles at the most then you can get away with dex around daratumumab.
The same with Tylenol and Benadryl that is often used as pre-med. I know a lot of people say, “Benadryl knocks me out for the next 6 to 12 hours.” After the first few doses of dara, you don’t really need that anymore.
Some of that is just experience, knowing that that’s what we did in the early trials, and that it’s okay to do it now. If you’re not seeing somebody that sees a lot of myeloma, you may just be on a plug-and-play where everything just gets recycled from cycle to cycle without necessarily reducing or taking them off to make life easier for the patient.
Dr. Costello: Dex is clearly the drug that everyone loves to hate. I think it’s important to say that dex is an oldie but a goodie. It’s been around for a long time. It is not a chemo, but it is designed inherently to kill myeloma.
That’s an important part because patients oftentimes ask, “Well, can I just stop it?” I want to say, “Yes, but remember, consider this part of your treatment regimen also.”
It is hard. I’ve heard people say, “It’s a dex day,” and I look at the spouse or the caregiver and say, “How’s it going?” Because that can affect your quality of life more than any of the other treatments do. People plan out their lives around the days they’re taking dex or the days after their dex.
It behooves us to really understand the importance of dex for all of these regimens because if it is playing a huge role in killing myeloma, then sometimes, it’s worth it.
If we are using it for an initial period of time to make a dent in the myeloma, for example, if we can get people off dex and continue the rest of the treatment, sometimes that makes it much more manageable for everyone across the board, let alone older, frailer patients.
At ASH, we heard about a trial [that] was one of the first, if not the first, randomized trial that was done specifically for frail myeloma patients. This trial took frailer patients, divided them in half, and said, “One half, you’re going to get Revlimid and dexamethasone. The other half, we’re going to do Revlimid, but instead of the dexamethasone, we’re going to do daratumumab.”
It’s similar to the MAIA study we’ve talked about when combining daratumumab and Rev, but this time with the hope of using as little dexamethasone as possible to see if these two groups, both receiving two medicines, can have good outcomes still without using the steroid in the study arm.
Now, I’ll say that these patients did get dex for the first two cycles, I think it was. That’s important. I think dex plays a role in helping to mitigate reactions to the daratumumab. Beyond that, maybe we can get rid of it.
They compared these two groups and said, “Dara-Rev, Rev-dex, how does it go?” Again, the dara-Rev group won. It is possible, we’ve learned, to get rid of the dex on our older, frailer patients.
[It] is [likely] going to be practice changing to say if we can drop the dex as soon as possible, patients may not have the same side effects: emotional lability, water retention, feeling swollen, appetite, [and] not sleeping at night.
If it’s not going to play a huge role, it’s in the best interest of everyone to get rid of it. This was the first time we’ve seen not only for a frail group but how we can successfully get rid of dex. I think it’s practice-changing.
Cindy, TPS: My house was always the cleanest on dex stays and most organized.
Dr. Costello: It just really affects everybody in different ways, but it’s life-changing.
FasTCAR T cell therapy
Cindy, TPS: Is there anything that we did not touch upon that you think we need to share about the newly diagnosed multiple myeloma patients from ASH?
Dr. Costello: One thing I really liked from ASH [is] super exciting. I don’t know if this is here to stay. It was only 17 patients, but the FasTCAR study in the newly diagnosed myeloma.
This was a Chinese group that developed a CAR T-cell. Right now, there [are] two different CAR T-cells that are approved by the FDA for refractory myeloma for patients who’ve had more than four prior lines of therapy. Again, these are patients who had myeloma [for] a long time. They’ve had lots of treatments.
Right now, it’s not available in the U.S. for patients who are just diagnosed. The Chinese designed a CAR T-cell and have started doing clinical trials, evaluating it for someone who’s just diagnosed with multiple myeloma.
In the U.S., the CAR T-cells that we have take five [or] six weeks, sometimes longer, to manufacture. [The Chinese study] figured out how to manufacture it in one to two days. The initial results they presented at ASH showed that it worked for 100% of the people they treated and 100% of those patients were MRD negative, meaning that they cleared out every last myeloma cell.
One of the things that we are very excited about is CAR T in general, but how can we use it earlier in the disease course? This is one of the first trials we’ve seen where somebody is trying exactly that with what seems like good success. Disclaimer: it’s a very small group of people. To be determined, but exciting.
Cindy, TPS: It was exciting. I like the idea of the FasTCAR because even the FasTCAR in the relapsed/refractory setting would be helpful because too many people are waiting too long or they don’t have [the] ability to wait.
Seeing a myeloma specialist
Cynthia, TPS: This is something that patients should be asking their doctors if their doctor didn’t tell them. You’re always giving us this little pep talk that all patients at some point should go see a myeloma specialist. Can you explain that again?
Dr. Lonial: The field is moving really fast. Things [change] once, twice, three times, or 10 times a year.
We’ve had multiple drugs approved in the last four years. Even through COVID, we still saw drug approvals. I think that the field is moving fast enough that if you have a really good general oncologist, they may be able to keep up to date, but they may not know the latest and greatest.
For that reason, I think having a myeloma center of record, if you will — a place that’s close to you, a team you feel comfortable with — that can partner with your local oncologist really guarantees that you’re getting access to the latest and greatest agents or combinations [and] that your team knows what approaches are going to be the most forward-thinking approaches to keep you going for the longest period of time.
Conclusion
Cindy, TPS: We talked to Doctors Lonial and Costello about newly diagnosed myeloma patients and treatment options for them. We learned about transplant-ineligible patients and the MAIA trial. We’ve talked about transplant-eligible patients, the GRIFFIN trial, and different ways to modify treatment. We also talked about stem cell transplant and if it’s really necessary.
It’s really important to be actively involved in your care. Take some of these points of information and have discussions with your doctor to see what may be the best treatment options for you.
Special thanks again to Janssen for its support of our independent patient education content. The Patient Story retains full editorial control.
Bladder Cancer Series: Through the Eyes of Black Women
“The Bladder Cancer Series,” focuses on Ebony, who was diagnosed with stage N2 bladder cancer, and LaSonya, who was diagnosed with high-grade bladder cancer.
In this series, they open up about their cancer journey, including their first symptoms, how they processed their diagnosis, how they decided on treatment options, and how they found support.
Ebony G.: I’m married. I have three sons. I’m an engineer by day.
I just want to live my best life and help others do the same.
LaSonya D.: I’m a variety of things. I’m a black woman, that’s the most obvious when you look at me, but I’m also a mother [and] a wife. I am a professor of nursing.
LaSonya D.
Initial symptoms
Ebony: After an annual visit with my gynecologist, they noticed a microscopic level of blood in my urine.
LaSonya: I had just recovered from an elective procedure and I was getting ready to go back to my regular work. One day, I noticed that I have blood in my urine.
Ebony on the day of her surgery
What was your reaction to the diagnosis?
Ebony: I was 45 when I was diagnosed with bladder cancer. I was like a ball of tears. At that moment, I remember thinking, “I’m going to die.”
It was pretty traumatic by myself in the office, but the nurse tried to reassure me and tell me, “You’re going to be okay.”
LaSonya: It’s devastating. How did I get this? No one in my family on either side has a history of cancer. How could this be? I don’t even know one black person that has this type of cancer.
I was a nervous wreck at that point. I felt so defeated and deflated. I just could not believe that this was happening to me.
Overview of bladder cancer
Dr. Samuel Washington: In general, we think of bladder cancer as either being muscle invasive, so growing into the muscle wall of the bladder, versus non-muscle invasive, where it’s just on the surface or on the lining of the inside of the bladder itself.
Treatment options for bladder cancer
Dr. Washington: Our treatments are different depending on which group you are in.
We know that patients for whom the bladder cancer has grown into the muscle, across the board, people are not getting what our guidelines say they should be getting. Depending on the cohort you’re thinking about, half will get some guideline-concordant treatment.
Now, there’s a question of guidelines being appropriate versus equitable, but we know that based on where you live, how far you are from a facility that treats bladder cancer routinely, [and] who you are, are all things that can impact the quality of care and the type of care that you get.
I think those are the key things that we see in bladder cancer that we hope to look at with some of our research.
Guidelines in general are a set of recommendations by our overarching governing body telling us, based on the most updated literature in research and the consensus statement of experts, what this patient should have based on the type of cancer or disease that they have. It’s taking the mystery out of medicine, but it’s really an algorithm. We find where these people fit in terms of staging and characteristics, we look at the guidelines, and they tell us what should offer the best outcomes for them.
Information for bladder cancer patients
Dr. Washington: There’s a lot of ongoing research for patients who are interested in more information about bladder cancer, the treatments, support groups, and ongoing research.
There are many outlets out there. Bladder Cancer Advocacy Network is one that is focused entirely on this. Ask your provider. “Are there resources that I can look at? Are there clinical trials or support groups for information?”
Importance of having a support system
LaSonya: Three weeks after diagnosis, I was able to have my surgery for the resection. [While] waiting to have my surgery, I had questions for this doctor. I knew right away that this was going to be very stressful, not just for me but for my family. I knew that in order for me to get through this, I was going to need help.
A lot of times, people think that you have to take everything on yourself, especially being from my culture. Mental health is very taboo. People take it as a weakness when you need to seek out help mentally. You always hear people say, “Be strong. Suck it up. You can do this. Don’t be weak-minded,” those kinds of things.
We are human beings. We are not robots and machines. We have feelings. I joined a bladder cancer support group on Facebook. I just started looking for bladder cancer support.
Ebony with part of her team at Duke Raleigh
Ebony: I remember looking in the social media group, trying to just scroll and see: who can I relate to?
The power of connection
LaSonya: There was something in the background of her picture that let me know that she was in the same sorority that I was. When I saw that, I just got so excited, especially because there [are] not very many black people at all [in] the support group. There isn’t a high percentage of black people that have bladder cancer. I was so excited.
Episode 2
The power of connection
LaSonya: When Ebony came on to the bladder cancer support group, she posted something and there was something in the background of her picture that let me know that she was in the same sorority that I was in.
Ebony: [She] was like, “OMG, hi, sorority sister. We’re here together.” That was so encouraging because I was looking for someone that looked like me. [I] hadn’t found anyone [who] looked like me that was fighting and winning at bladder cancer. To find her was huge for me because it’s like, “Yes, we can absolutely identify on even more levels.”
LaSonya: I got so excited, especially because there [were] not very many black people at all in the support group. There’s just not a high percentage of black people that have bladder cancer.
Ebony: It was instant. You know everything that I’m feeling. You can relate specifically to the loss of hair. You can relate specifically to darkening complexions. [The chemotherapy] also made certain parts of my skin darker. You can relate specifically to all those things.
LaSonya: It’s very important. It keeps you going. It empowers you.
Black women have higher stages of the disease & worse survival rates
Ebony: We initially thought it was a UTI so I was prescribed an antibiotic and then thought, “Okay, we’re good to go.” It kept going. What’s going on?
[I felt] despair at some points because I just really didn’t know. I was wondering if there was something underlying. I was Googling things [and] trying to figure [it] out. [I was] just confused and lost as to how the professionals don’t know.
I remember thinking, I trusted you for a year and a half to try to find something. What was it about everything that has gone on in the past year and a half where you didn’t find anything?
LaSonya: It seemed like it was a lot of blood. I saw some blood clots and I was thinking, I know I’m not on my menstrual cycle. What is going on? Maybe it’s something from my surgical procedure.
I called my surgeon and he said, “It doesn’t seem like something related to your surgery. Let’s do a urinalysis and see if you have a urinary tract infection.” I did that [and] it came back negative for infection, but positive for blood.
Signs & symptoms of bladder cancer “tend to be missed” in women
Dr. Samuel Washington: Women who are found to have repeated tests of blood in the urine or see blood in the urine sometimes can be attributed to recurrent urinary tract infections. Whether or not there’s a positive urine culture [or] urine test showing bacteria, they will be routinely treated with antibiotics.
But what is missing is the workup to make sure that it’s not cancer that’s hiding there and causing the bleeding. That can lead to delays as people get treated with antibiotics and you don’t see any change in the symptoms. It’s because we’re not treating it correctly.
Differences in survival: access to care and type of care
Dr. Washington: A lot of the research that I’ve looked at is around race as a social construct, so not just biology and seeing that there’s a [biological] difference and that that is the cause of the differences and outcomes that we’re seeing, but how society is framing these people: black vs. white, insured vs. not, educated vs. not. All these different identities impact one another to lead to these outcomes that we’re seeing that our differences between groups.
I commonly say no one’s intentionally contributing to disparities but also, very few of us are actively monitoring our own outcomes. The educational materials that we use, the required health literacy level for that, how we provide access to care for different patients, things that could help patients in terms of transportation, social work, and so on. Those things are not commonly measured at the same level that we monitor cancer diagnoses.
Representation matters: finding the right doctor
LaSonya: I was looking for a doctor that looked like me because I felt like I could trust a doctor that looked like me.
It’s just the things I don’t have to explain [like] the culture. There are certain things that when you’re holistically looking at a person or a patient, in my perspective, when I’m taking care of patients, I look at them holistically.
Overcoming obstacles
Ebony: I want people to know: you’re not the only one. I have fought through this.
I want to be the evidence, the example. I try to tell people, “I do consider myself a miracle and if you’re ever looking for evidence to help encourage you, let me be your evidence. You can fight this and win.”
Episode 3
The impacts of bladder cancer
Ebony: As a Black woman, it actually takes a long time for our hair to get to the lengths we enjoy.
[I have] a lot of pride and joy in my hair. I call it my crown. For about seven or eight years, I decided to become natural so [I didn’t use] any chemical products in my hair [or] any relaxers to relax my curl pattern.
To find out it’s all going to come out, I think to myself, Is it going to grow back?
I was devastated. How am I going to manage not having hair? That was honestly the tip of all of the side effects that were going to come from it but the initial thought was [losing my] hair.
I remember getting it cut and coming home that night. My husband started crying. He was like, “You’re really having to do this. Here we go.”
3 main paths after the bladder removal surgery
Ebony: There were a few options. I could have the bag outside of the body. My brain was like, Okay, that’s the option. [A] bag outside of my body that I would need to empty.
I was wondering how my clothes are going to fit. Am I going to have to have additional things [I would need] to use the bathroom? Am I going to have to change what I wear? I usually would wear fitted things. Am I going to have this bag that’s going to dictate [that]? Am I still going to be what I thought was attractive? You name it, I thought all those thoughts.
Then there was an Indiana pouch, which my doctor didn’t do, and the neobladder, which is what I decided to go with.
Ebony recovering from surgery
How much life changed after the bladder removal surgery
Ebony: My first appointment with the urologist was accompanied [by] this 3-inch binder [with] tons of information. There were sections [that talked] about what could happen after the surgery. One of those things was you could lose all ability to control how you use the bathroom. Those were the fears that I had.
[It covered] how it could impact your sexual relationships, your sexual relationship with your spouse. I remember thinking, Okay, this is a whole lot more than what I initially bargained for.
LaSonya: When you’re thinking about being married, young, and not having a vagina, that could be traumatic to your relationship. I never would have thought to ask but somebody in my support group brought it up. I talked to her and she became one of my close friends, too.
When she had her bladder removal surgery, they removed all of her vagina except for maybe two inches, which [meant] that she would have to come back later and have a reconstruction of her vagina. I was like, “Oh no, that is what I’m not doing. I don’t have [a] muscle-invasive disease so it’s not out of my bladder. I do not want to have no vagina.”
I was able to consult with the plastic surgeon. He went through the procedure. I said, “If they get in there and there’s a problem, I expect to wake up and still have a vagina.” He said, “If they get in there and they have to remove everything, then I’ll either take part of your muscle from your thigh or from your abdomen and I will make you a vagina. You’re not going to wake up and not have a vagina no matter what.”
It seems like something small when you have cancer, but it’s not. It’s still quality of life.
One of the things I was able to tell Ebony was, “Make sure you talk to them about vaginal sparing [so] you don’t wake up like another friend [who] only [has] a two-inch vagina and nobody told you anything.”
There [have] been a lot of people on the site whose partners left them. They have cancer and their partners leave. Because mentally, they can’t handle it or this situation. They can’t wrap their head around the fact that their sex life is going to be very different.
Ebony: I remember thinking, “As a woman, am I going to be able to help you meet your needs? Are you going to be disappointed still being married to me? Because now this ‘for better or worse’ is looking a whole lot worse than when we started 16 years ago.”
I would find myself stressing [about] what the outcome would be. That’s when my husband would come back and say, “Right here. We’re going to conquer the day. We’re just going to conquer the day.”
LaSonya: This is important. This is quality of life. It’s not just about living. It’s living your life abundantly and having the best life that you can possibly have.
Episode 4
The power of the patient
Ebony: At the end of the day, no one knows your body like you do.
I just challenge everyone out there. Doctors are doctors, but they are practicing medicine. They’re practicing, so they will not know everything. You know your body more than anyone else.
What the medical industry can do is put more faces in the forefront of people who are doing well, who are receiving the treatment, who have found their way, [and] who are winners. Not only people who have won the fight, but put people who are open and willing to help people win the fight.
We need to see that the system cares about us. We need to see that, because for decades, we’ve seen so many systems that don’t.
LaSonya: He had a picture in his mind of who I was and what my life was like. He already had his own stereotypical thoughts about who I was.
I actually worked in the same healthcare organization that he worked in. He did not treat me well as a patient. Thankfully, because I’m a clinician, I was able to identify that right away.
Go with your gut. If you feel like something is not quite right, get a second opinion. You’re entitled to a second opinion and some insurance will even pay for a third opinion. Do not feel like you’re stuck with that person.
I never have been one to put all my trust in another human being. I felt like I needed to do my own research and have my own questions ready so that I know that I’m getting the best care possible. The experience I have with urologists made it even [clearer] to me that my approach is the best approach for me. You have to do what’s right for you. Get all the information that you possibly can and then you decide what’s best for you. You’re the one that’s going to have to live with your decision.
Black urologists in the U.S. are extremely underrepresented
Dr. Washington: Not infrequently, a Black patient will say that they’re happy to see me or someone that looks like me. It may not be important for everyone, but I think for some patients, it is a game changer in their comfort with the care that they’re getting.
[In] the urologic workforce, less than 3% of us are Black. A much smaller percentage when you start to chip away and look at different subspecialties.
Often, I think what it comes down to is for them, there is a shared life experience that we have that provides more comfort. That doesn’t mean that other practitioners that don’t look like them will not offer good care, but it does potentially provide a level of comfort that is not something that they’ve encountered before.
Myelofibrosis Highlights from ASH 2022: What Patients & Caregivers Need to Know
Patient advocate Ruth Fein has been living with MPN for nearly 30 years. Despite the diagnosis, she lives a very active and full life.
In this conversation, she speaks with Dr. Serge Verstovsek, founder and director of the largest MPN clinical research center in the world, and Dr. Naveen Pemmaraju, director of MD Anderson’s rare disease program and executive director of the Cancer Network.
They discuss cutting-edge treatments and therapies, combination therapy as a focus in treating myelofibrosis, and the importance of being an educated patient and being your own advocate.
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.
Ruth Fein, Myelofibrosis Patient: I’m an MPN patient with myelofibrosis. I’ve been living with one form or another of an MPN for nearly 30 years. When I was first diagnosed in the 90s, [it wasn’t] even called a blood disorder.
What I went through in diagnosis is very different than what’s happening today, where the initial diagnosis is that Big C, which of course is a fear I didn’t have to deal with. But now with myelofibrosis, it’s a game changer.
I’m very fortunate, as we all are, that research is moving so rapidly, changing our prognosis as the research advances. In fact, [I’ve been] on a clinical trial [for] almost three years now.
I remember it really clearly. I was in New York. It was supposed to be a routine appointment. Rain was pouring hard. I was soaking wet. I was carrying around my luggage. I sat down for my appointment with my super specialist and I’d had a bone marrow biopsy that surprised me. I had a new diagnosis. All of a sudden, I went from ET (essential thrombocythemia) to PV (polycythemia vera) to myelofibrosis, and that’s the progression people are worried about.
Immediately, I felt shocked. Then three hours later, I felt completely comfortable.
I’m seeing a super MPN specialist and she said, “I have the perfect clinical trial for you.” I got all the information [and] decided it made sense for me — that was three years ago and I am doing incredibly well.
I’m still gardening. I’m a health and science writer. I garden, I walk every day, I cycle, I swim. I’m the mother of two adult boys, a wife of a very active, wonderful man, and I happen to be a patient with myelofibrosis as opposed to my life being about myelofibrosis. My life is very full.
There’s so much we can do as patients to ensure that we’re getting the best care we can [get] to help us live longer and to live well as long as we’re here. And that’s why we have these conversations so we can bring you the expertise and the collective wisdom of the super specialists in the world.
Today, it’s all about MPN, specifically myelofibrosis. Two incredible docs are lending their insights so you can take your questions to your own doctors.
Dr. Serge Verstovsek with MD Anderson, founder and director of the largest MPN clinical research center in the world, and Dr. Naveen Pemmaraju, also with MD Anderson, who is the director of its rare disease program and executive director of the Cancer Network.
We’re having this discussion coming out of the biggest meeting of the top blood cancer and MPN specialists in the world. Our goal is to highlight what’s likely to be most impactful for those of us dealing with myelofibrosis, for both patients and caregivers.
We have some promising data on a therapy that could potentially not just address myelofibrosis symptoms but eliminate the disease for some of us. That’s very early, but it’s exciting as it was picked to be one of just a handful of highlighted sessions out of thousands at this conference that just wrapped up.
First, let’s set the stage. Most myelofibrosis patients and care partners go to a community care center. That’s, of course, where I started 20 years [ago] Even if a lot of what we’re going to talk about today is still potential or in clinical studies, what are the questions patients and caregivers should be asking?
The importance of being your own advocate
Dr. Serge Verstovsek: Thank you very much for having me. It’s a pleasure to share my excitement with you.
First, a little proactive approach is always good to learn about the condition and the disease and see how the treating doctor is about providing the answers. It’s a team effort. Nobody knows everything. Be mindful of that.
Then, if necessary, go for a second opinion [with an] MPN specialist because ideally, there would be a team — a local doctor, the MPN specialist, and the patient — who decides what to do at what time. The patient is actually in charge. We are only suggesting.
Be an advocate for yourself because it’s a lifelong condition, which has [the] potential to shorten [your] life. Engage and don’t be mad or sad. There is a lot to do together with the local doctor [and] with the MPN specialist.
Ask questions. If there are no answers, seek the answer. Be one of the contributors altogether to improve your own condition.
Be an active participant. As I always say, who is the decision maker? It’s the patient. The educated patient, engaged patient is the best patient.
Cutting-edge treatments and therapies
Ruth: Great tips, Dr. Verstovsek. You’ve been leading the way in MPN research for decades, as many of us know, and it seems there have been so many developments in terms of cutting-edge treatments and new therapies for myelofibrosis. What should patients and their partners know about that?
Dr. Verstovsek: You’re right, there is a lot going on in the MPN field. I like to divide this [between] excitement about what’s coming soon and what’s coming maybe not soon enough.
Back in 2004, when I really engaged in MPN, there was no standard of care and there was no study or studies. We were trying to seek friendly people in different companies where we would perhaps use the drugs that are already on the market for something else, like thalidomide or lenalidomide.
People probably resonate well with these drugs. We try them and other colleagues in the field try them in myelofibrosis. They do help but not too much and not too often. Then the discovery of the abnormalities — JAK2 and others — led to [a] real interest in developing more specific drugs for myelofibrosis.
Where we are now, it’s like night and day. Now, there are three approved drugs for myelofibrosis. This fourth one, momelotinib, may be [approved] next summer. So four and numerous phase 3 studies. Numerous studies in general so that you have options. We just seek more patient participation.
Ruth: Thank you, Dr. Vertsovsek. Let’s dive into what many of us know more about — JAK inhibitors. We have 3 FDA-approved ones now:
Ruxolitinib (Jakafi)
Fedratinib (Inrebic)
Pacritinib (Vonjo)
There was an update on pacritinib for myelofibrosis patients. Can you share more?
Dr. Verstovsek: [Pacritinib] is a JAK inhibitor that decreases the spleen [and] improves the quality of life.
It was approved in February 2022 for patients with low platelets, which is below 50, because it does not suppress the blood cell count like ruxolitinib or fedratinib, the other JAK inhibitors that have already been on the market for quite some time. The novelty is that it can improve anemia in some patients and that appears to be added value to it.
I actually tell my patients I treat with pacritinib — and these are the ones with the lower platelets — [and] that it’s not going to suppress your blood cell count. It may actually improve the anemia and it is good for the spleen and symptoms.
There is added value now that we know of, with [a] very [good] description of that value at ASH 2022. That’s on the recently approved drug.
Much enthusiasm is about a JAK inhibitor called momelotinib, which will be likely approved by summer 2023 because the application was submitted and it’s under review by the FDA.
This particular drug is different. It’s a pill like all the other JAK inhibitors. It may improve the symptoms and the spleen like all the other JAK inhibitors, but the real value is that anemia benefit. That is the primary reason why you would use momelotinib.
In a phase 3 randomized study that was done during COVID, it was proven to be very valuable for patients after initial ruxolitinib for control of the anemia, improving the anemia, improving the symptoms, and improving the spleen.
We expect that momelotinib, which is also very safe, will be one of the major new drugs particularly in the second-line setting once people fail ruxolitinib. All of these came from the ASH 2022 analysis. And it’s durable.
We will then have choices. We would have pacritinib for people with very low platelets or momelotinib for patients with anemia. We would optimize our care of patients for a longer period of time because we have been limited in what we could do once ruxolitinib fails.
Dr. Naveen Pemmaraju: I hope — and I know all my colleagues do, too — that we have dozens of these drugs to offer to different patients. Hopefully, one day we have a biological, molecular approach to selecting them as well.
Combination therapy to treat myelofibrosis
Ruth: Dr. Pemmaraju, let’s move to another big headline — combination therapy as a focus in treating myelofibrosis patients.
Dr. Pemmaraju: Combination therapy not only in the relapsed/refractory setting but we’re also investigating it now in the front-line setting. We have to keep in mind: how is the patient tolerating? Are there too many side effects? What is the actual benefit of adding the second agent compared to the JAK inhibitor alone?
Ruth: This always goes back to not all patients are alike. There isn’t a cookie-cutter approach. One thing I always say about MPNs and myelofibrosis is the only predictable thing is that they’re not predictable.
Dr. Pemmaraju: We always talk about personalized, individualized, targeted therapy. This is the era that we’re in now. Each patient may have a different comorbidity profile — other diseases and diagnoses that they carry outside of the myelofibrosis.
[They have] different ways they metabolize drugs [and] different molecular mutations in their myelofibrosis. We’re in a whole new era of trying to select either clinical trial drugs or, hopefully, one day, even standard-of-care drugs.
Ruth: Thank you, Dr. Pemmaraju. Let’s talk about some of these combinations. One update has been on a BCL inhibitor, navitoclax, in combination with a JAK inhibitor. Where would that come in?
Dr. Pemmaraju: This is excellent. We all work on these clinical trials together. I think the navitoclax agent, BC-LXL, is important. It’s not yet FDA-approved for anything.
What it’s showing is that in myelofibrosis in particular, either as a single agent or in combination with [a] JAK inhibitor, it has possible disease-modifying effects.
We showed very good overall survival in suboptimal patients who are already on a JAK inhibitor and added the navitoclax. Some variant allele fraction reduction, some bone marrow fibrosis improvement.
The navitoclax agent is now in phase 3 randomized global study: ruxolitinib plus navitoclax versus ruxolitinib alone essentially. We hope to have those results in [2023] so that we know if the combination approach is beneficial to our patients in the front-line, untreated setting.
Ruth: I want to talk about another phase 3 trial, a drug close to my heart: pelabresib. That’s the trial that I’ve been on for three years and that’s used again with a JAK inhibitor. I understand the results have been very promising. In fact, my doctor calls me a poster child for this clinical study.
Dr. Pemmaraju: Yeah, exactly right. In this class of combinations, we mentioned the BC-LXL strategy and navitoclax. You also have this bromodomain or BET inhibition with pelabresib.
Very encouraging results there as well, which again started out in the single-agent, relapsed/refractory setting and then was added on to the ruxolitinib and now is being investigated in patients. Again, [the] same thing: phase 3 randomized study, front-line.
For you and I that have been in the field for longer than a decade, what this marks is for the first time, we’re moving combinations into the front-line setting. That means a patient who’s newly diagnosed with myelofibrosis is then put forward with two drugs instead of one. That’s the big deal here and we’re starting to hear those results.
What should patients consider when seeking treatment?
Ruth: This is really exciting because we’re talking about options here. But if you were to say anything more as a specialist, a super specialist in myelofibrosis and other MPNs, you are seeing a patient and you’re making decisions on which way to go with therapy. What other considerations are there since you have so many options now, thankfully?
Dr. Verstovsek: There is no real reason to switch right away. If one thing doesn’t work, maybe you can optimize it. What does this mean? This means that you can combine things together.
There are a number of medications that are not JAK inhibitors that are improving the red blood cell count, the spleen, or symptoms in myelofibrosis patients [and] that can be combined. [They are] being tested in advanced clinical studies to help the patients right from day one. Day one [means] the patient needs the therapy [and is] newly diagnosed.
Why don’t we use two drugs together instead of one? There are medications like pelabresib, parsaclisib, navitoclax, or luspatercept. Basically, giving four is to enhance what the JAK inhibitors do. More of the spleen [and] symptoms control and perhaps much more durable.
Luspatercept is for anemia control while you are treating with a JAK inhibitor or ruxolitinib. One aspect of drug development [is] starting with the best combination from day one. If you start with ruxolitinib alone, you add in suboptimal responders, [which are] people who benefit but not optimally.
You add another agent later. That’s like parsaclisib, another daily pill that was proven in a presentation in ASH to be very valuable in people who are already on JAK inhibitors [and] doing okay, but there is room for improvement. You add parsaclisib on top of it, another pill, and you enhance the spleen or symptom control.
We [don’t] necessarily need to go from one drug to another drug to another drug, which is the common path, and it’s always there to do. Maybe we need to talk about combinations in specific clinical situations. We are developing multiple different combinations for different clinical scenarios.
One will be better than the other or applicable more in one patient than the other. If that doesn’t work, you go to another drug and then maybe another combination. Maybe within the next three to five years, we’ll have a number of choices not just as a single agent but the combinations.
Deciding which combination to try first
Ruth: How do you decide which combination first? I know there was data also presented [about] ruxolitinib with different agents, including novel agents such as selinexor, [which was] first approved in multiple myeloma. Now it’s being used in myelofibrosis treatment research. Can you shed some light on this?
Dr. Verstovsek: We have been studying several combinations already. I mentioned those medications, but there are newcomers, which may be better. Difficult to say from the beginning, but selinexor is another drug that is approved for multiple myeloma that may be active in myelofibrosis. It seems so from the preliminary results.
Interestingly, there was also a presentation by Dr. Kiladjian from France on adding interferon to ruxolitinib, which also enhanced the ability of ruxolitinib to do the job on the spleen and symptoms. There were some intriguing results on molecular improvements as well.
Perhaps it’s not only about combinations with a completely new, unproven yet, or completely investigational drug. Sometimes you may just look back in time and say, “Is there something there that I can use that is already established as [an] agent or a drug interferon?”
We are having a larger umbrella here without limitations in our attempts to optimize the care for our patients. It’s pretty exciting. You can have selinexor as an example. We think that’s approved for something else so much different than myeloma. You try it in a completely out-of-common-sense approach, like myelofibrosis, and it does work. We’ll follow that particular clinical study of that combination very carefully as well.
Dr. Pemmaraju: There’s this new era of novel drugs. They either come straight out of the lab or they’re borrowed from some of the other blood cancers. Selinexor is a novel one. It’s actually already US FDA-approved, for example, in multiple myeloma, but sometimes, the doses are higher or lower [or] mechanisms of action combinations.
Again, that combination, that new drug is following the same pattern we’ve seen, which is single-agent activity for relapsed/refractory and then now moving into the front line in combination with ruxolitinib, a JAK inhibitor.
Kinase inhibitors
Ruth: One other area of inhibition, if you will. You mentioned these different kinds of inhibitors. Along the way, you mentioned kinase inhibition. That’s something that could be coming over the horizon.
Dr. Pemmaraju: Yes, exactly. The third category outside of these two is what’s called PI3 kinase inhibition. Kinase, the word itself when it’s used, really means messenger or pathway in some of these cancer cells.
We didn’t have these clinical trials five [or] seven years ago. What we’re starting to do now is pick out individual pathways in the cancer myelofibrosis cell outside of JAK-STAT.
[We’re] trying to pick pathways that may complement JAK-STAT so that you can get a dual or combined approach. That’s what a lot of these phase 2 and phase 3 trials are doing and even more novel agents than these first three that we’re talking about.
Treatment, health, and transplants
Ruth: One important point here is the thought [that] transplants can be very intimidating for a lot of people. Do you feel that some of these newer therapies or combinations will help alleviate the need to go there?
Dr. Verstovsek: I think, at the moment, it’s the other way around. We are trying to improve the condition of the patients and make them physically better, metabolism to improve, inflammation to be controlled well, and get the patients to transplant in the best possible shape.
At the moment, transplant is still the only procedure that can eliminate disease and cure patients. There are limitations on the medications. We are trying hard to extend the benefit of pills, but they have limitations. Nothing really works forever.
I hope that there are actually more patients going through the transplant as we improve their condition and then the transplant success is even higher when you get the “healthier” patients.
Unless we develop the drugs, something that would potentially eliminate disease antibody in calreticulin-mutated patients. This is in the future; it’s not even in the studies yet [of anything that] has that potential. At the moment, we encourage people to go through the transplant when they are in the best possible shape on a JAK inhibitor.
Dr. Pemmaraju: Allogeneic stem cell transplant remains the only curative modality for our patients with myelofibrosis. It’s tough to say that because it’s such a difficult procedure for many of our patients. Many of our patients are older [or have] comorbidities.
Across the world, as I meet with patients and doctors, they don’t have access [to] or follow-up for it. That’s tough. That’s the hope and optimism that I personally have: can we offer these combinations or other novel agents to try to cure the disease outside of stem cell treatment?
Unfortunately, I would say stem cell transplant is the only curative option, but again, unfortunately, it’s not available to the vast majority of our patients.
Ruth: Speaking of cure, that is the big splash that just came out of this ASH meeting. Dr. Verstovsek, what was all that buzz about?
Dr. Verstovsek: It has to do with the development of a possible new therapy. The key word is “possible” because the presentation was on preclinical testing. [It’s a] possible new therapy for a third of the patients with myelofibrosis or ET (essential thrombocythemia) that have a specific mutation: calreticulin mutation.
Everybody probably knows about the JAK2 mutation, but there are a couple of other mutations that are important that are mutually exclusive. You have JAK2 mutation, calreticulin mutation, [and] MPL mutation. These are mutually exclusive and present in about 90% of the patients with myelofibrosis and 90% of patients with ET (essential thrombocytopenia).
What they do is activate inside the bone marrow cell this pathway that we call a cascade of protein. My patients call it a highway. It jacks that highway. It’s always active because of these driver mutations. That makes your cells grow and causes inflammation.
Because this mutated protein is on the surface of the cells, we can identify malignant cells. This is a marker of [a] malignant cell. Now, the presentation was on [the] development of [an] antibody. Another construct would be attaching specifically to the cell with the mutated calreticulin and basically [letting] it die off over time, so elimination of the disease.
This is a potential of such a therapy, [an] antibody for mutated calreticulin, which will be given to patients with myelofibrosis or ET that have calreticulin mutation by genetic testing. It’s easy to do and that’s the potential of inhibiting the growth of malignant cells specifically. Elimination of the malignant ones is what everybody is talking about.
We hope that in the near future, perhaps [in] 2023, we’ll have a study of it with the antibody for patients with calreticulin mutation. Extremely exciting because we usually talk about improvement in the bone marrow function — anemia needs to improve, decrease in symptoms, or smaller spleen. This has a potential [for] what we call molecular response — decreasing the number or eliminating potentially the malignant cells.
Ruth: That is exciting! To be clear, this calreticulin-targeting therapy is not in [a] clinical trial yet, so the hope would be for it to enter a phase 1, first in humans, study hopefully this year.
Speaking of clinical trials, I’m a part of one now. You’re trying to get more people to know about and ultimately participate in clinical trials, too?
Dr. Verstovsek: Participation in the study would be the ultimate goal in my view from the patient’s perspective. You get the standard, but you get something extra on top to make it even better. Why not?
From your own perspective and from the perspective of benefit to the community of MPN patients, why not seek participation in a clinical study if it’s not mentioned already by the treating doctor?
Importance of being an educated patient
Ruth: That’s exciting because it helps people understand the importance of where all cancer therapies are hopefully heading into with understanding more data about the person. In this case, the mutation.
What is your message to patients and their care partners [or] caregivers about the importance of making sure they understand or [are] asking questions of their doctors about mutations?
Dr. Verstovsek: The best patient is [an] educated patient. In our own practice, we try to provide the patients [with] everything we know about their condition unless the patient says, “No, no, no, you are the doctor. Don’t tell me anything,” which is not very common.
We have a very enthusiastic group of patients that would like to know everything and be part of decision-making and planning, which is the optimal care in my view. We embrace everybody and we want everybody to participate and understand.
The disease is there for some reason. We cannot really say, “This is why it happened,” but we can describe it very well by molecular testing, the testing of chromosomes, the testing for fibrosis grade in the bone marrow, and as you measure the spleen and the red blood cells.
You want to know everything you can. Sometimes, that information is useful for therapeutic decision-making; sometimes, it’s not. Patient education and understanding of what it is, what can we do about it, and how is very important.
Calreticulin mutation in the future — some reservations here — can potentially really make a difference for these patients. We’ll see.
Conclusion
Ruth: It seems that two things are going on. One is medical science is moving forward. Personalized medicine is the name of the game and patients need to have an active dialogue with their doctor as to where they are now with their myelofibrosis and what applies, either in a trial or with an approved or newly approved medicine, right?
Dr. Pemmaraju: You could not have said that better. I really want to emphasize what you said because we are now beyond the point where we only had one treatment option or one standard-of-care option. That’s awesome.
Dr. Verstovsek: I always try to emphasize to our colleagues in the field and the patients themselves who are savvy and go online that there is so much going on. Get engaged. Standard care came to become [the] standard of care from research. It didn’t just appear.
The combination [and] new drugs that are in development, potentially better than the standard of care, are subject to research. That’s how you do it. We are here to team up with the companies, with the regulators, and with the patients all together for [the] betterment of therapy for myelofibrosis. Be alert. A lot is going on. Be a participant.
Ruth: Thank you both, Dr. Verstovsek and Dr. Pemmaraju, for joining us in this conversation to help us, myelofibrosis patients and care partners.
Dr. Pemmaraju: Thank you so much and thanks for having me.
Dr. Verstovsek: My pleasure. I hope it was useful to everybody. I’m here to help.
Ruth: Thank you to the patients and loved ones who are so engaged in understanding more. There is a lot to be hopeful for.
Special thanks again to Karyopharm Therapeutics for its support of our independent patient education content. The Patient Story retains full editorial control.
Relapsed/Refractory Multiple Myeloma Highlights from ASH 2022
The Role of Bispecifics in the Treatment of Relapsed/Refractory Multiple Myeloma
Patient advocate Jack Aiello is a 28-year survivor of multiple myeloma. When he was diagnosed, he was told he would only have two to three years to live and only two treatment options were available.
Jack underwent two transplants and then went onto a clinical trial for thalidomide but nothing worked until a third transplant.
In this conversation, he speaks with Dr. Ajai Chari, the Director of Clinical Research at the Multiple Myeloma Program at Mount Sinai in New York and Dr. Sandy Wong, a blood disease specialist at University of California, San Francisco, with a special interest in multiple myeloma.
They discuss game-changing treatments for relapsed/refractory patients, bispecific antibodies, treatment side effects, and emerging clinical trials.
Thank you to Janssen Oncology & AbbVie for their support of our patient education program! The Patient Story retains full editorial control over all content.
This interview has been edited for clarity. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
For today’s newly diagnosed patient, you can be more optimistic about your diagnosis than [at] any time in history. We don’t have a cure [but] we have treatments available to manage this disease.
Jack Aiello
Introduction
Jack Aiello: I’m a 28-year survivor of multiple myeloma. When I was diagnosed in 1995, the doctor told me I had two to three years to live and [that] there were only two treatment options available. I remember going home to my wife, [telling] her the little bit I understood about this disease, and, suffice it to say, we shared a good cry.
I had kids who were 16, 14, and 10 years old at the time. I knew I was going to have to go to the hospital so I just told them that there was something wrong with my blood and I was going to have to have it treated. But I wondered, would I be seeing the kids graduate from high school? Who was going to teach my son to hit a curveball in Little League? Who was going to pay for them [to go] to college? It was a difficult time.
Since then, we’ve had 13 or 14 new drugs approved by the FDA, more combinations of these drugs, and even more are in clinical trials today.
I really believe that for today’s newly diagnosed patient, you can be more optimistic about your diagnosis than [at] any time in history. We don’t have a cure [but] we have treatments available to manage this disease.
For relapse/refractory patients, you’ll hear some great results from the recent ASH meeting. Many abstract presentations were on the topic of drugs and a category of drugs called bispecific antibodies.
To help us understand more are Drs. Ajai Chari and Dr. Sandy Wong.
Dr. Ajai Chari is the Director of Clinical Research at the Multiple Myeloma Program at Mount Sinai in New York.
Let’s kick off the conversation with what was the big buzz this year: bispecific antibodies. We’ve heard of monoclonal antibodies like daratumumab. Most recently, the FDA approved a bispecific antibody called teclistamab or Tecvayli. What exactly is a bispecific?
Bispecific antibodies
Dr. Ajai Chari: It’s a really exciting time. I’ll start with one of my favorite stories about the development of immunologic treatments in all humans. In [the] 1980s, the Nobel Prize was actually given for creating a standard antibody that was taken by fusing a myeloma cell with a spleen cell.
Every human antibody that we use — whether it’s for COVID, autoimmune diseases, [or] cancers — owes its legacy to myeloma. The first naked antibody, which is this Y-shaped structure, was not approved [for] myeloma until about 30 years after that Nobel Prize was given even though antibodies were helping everybody else.
The first naked antibodies were daratumumab and elotuzumab. The ends of the Y-shape bind to one target and typically that’s the myeloma cell or whatever cancer cell.
It’s either a handcuff or double-sided tape. Basically, what it does is it takes one side of the Y, binds to a T-cell through a target known as CD3, and the other side can bind to a myeloma cell. You can change that up based on the protein.
The one that’s commercially available now that’s called teclistamab binds CD3 and the T-cells to BCMA or B-cell maturation antigen.
It’s remarkable how well these agents are working.
Dr. Ajai Chari
Jack: So the difference between that and a monoclonal antibody is the monoclonal antibody doesn’t have that second arm connecting to the T cell, is that correct?
Dr. Sandy Wong: That’s correct. Monoclonal antibodies activate the immune system in a different way.
For example, drugs like daratumumab or isatuximab activate the immune system [in] several ways. One is they act almost like Post-It Notes, if you will, where they flag cells [that] are not supposed to be there, i.e. the myeloma cells, and that leaves the immune system to know, “Hey, this is not supposed to be there. Let’s get rid of this myeloma cell.” That’s how a monoclonal antibody works.
Bispecific T-cell engagers physically attach to T cells and bring the T cells in physical proximity with the myeloma cells. The T cells get rid of myeloma cells that [are] not supposed to be there so they secrete their toxins, etc., and get rid of the myeloma cells. They work very differently.
Dr. Chari: It’s remarkable how well these agents are working. Basically, it’s an off-the-shelf product so that’s important.
A lot of people may have heard about CAR Ts that also target BCMA, but the difference is this is ready to go. It doesn’t have to be manufactured for each patient.
You don’t need to go through the T cell collection, manufacturing, and waiting. This is an off-the-shelf product. That’s the same for every patient with myeloma.
What the drugs do is basically traffic the T cells in our bodies to whatever you’re trying to bring them to. In this case, the T cells in a patient are preexisting or trafficked to wherever the myeloma is, and when the T-cells are brought right up against the cancer, they recognize the cancer.
They release certain chemicals or cytokines that poke holes in the cancer cell and that lead to cell death. I say it’s like bringing your army straight to the enemy, as opposed to hoping and praying that they find the right place to go.
It’s a mind-changing, game-changing era that we’re in with this immunotherapy treatment.
Dr. Chari
Treatment for relapsed/refractory patients
Jack: The teclistamab that was just approved and the other bispecifics, just to let the [readers] know, are so far for relapsed/refractory patients. Those [are] patients who have gone through several lines of previous treatments before getting to these bispecifics. Is that right?
Dr. Chari: Yeah, that’s exactly right. Just to put this whole space into context, about five [or] six years ago, the way drugs get approved is that they’re first tested in heavily treated patients — as you mentioned, relapsed/refractory myeloma.
The benchmark to get a new drug approved was about [a] 20-30% response rate, lasting about three to four months. Those numbers sound modest, but we have to keep in mind those are in patients who had exhausted all available therapies.
When I started in myeloma 17 years ago, thalidomide was just coming on the scene. At that point, [to treat] relapsed/refractory, you had thalidomide and maybe a transplant. Now, typically, we’re talking about the big five drugs:
lenalidomide (Revlimid)
pomalidomide (Pomalyst)
bortezomib (Velcade)
carfilzomib (Kyprolis)
CD38 antibodies, such as daratumumab or isatuximab
That is a very different patient than somebody who just had had thalidomide. As we keep approving drugs, this unmet need, which is patients who have exhausted their currently available therapies, keeps changing.
In spite of that, what’s remarkable about the entire T cell redirection, whether it’s bispecific or CAR T, is we’re saying 70-100% [response rate] is the new 20-30%. That’s how many patients are responding to these drugs. Even though these are much, much sicker patients and have had more treatments [and] more drugs, we’re getting better responses.
That’s what’s really exciting. I literally have patients [with] whom we had discussed hospice a few years ago and now they’re in their deepest, longest remission they’ve had in years. It’s a mind-changing, game-changing era that we’re in with this immunotherapy treatment.
How is talquetamab is different from other bispecifics?
Jack: For one who’s been watching new treatments being developed and now seeing [a] 60% or 70% response rate, it’s pretty incredible.
Dr. Chari, you presented a different bispecific called talquetamab, also from Janssen, the same manufacturer of teclistamab. Can you share the results of this trial and what might make talquetamab different from other bispecifics?
Dr. Chari: First of all, this work takes [a] tremendous team, starting with the patients and their caregivers and then the entire study team, Janssen, the pharmaceutical, the FDA, and other regulatory agencies.
With the phase 1 portion of the study, we’re looking to just find the safety and what’s the right dose and schedule. The phase 1 study just got published in [the] New England Journal so that was very exciting. It was also a large phase 1 study with over 200 patients.
Efficacy and safety (how well it works in the safety profile) were then validated in this phase 2 study and that’s what we presented at ASH [2022]. The phase 2 study had 3 major cohorts of patients:
One got a dose of what we call 0.4 mg per kg subcutaneously every week
A second cohort got 0.8 mg per kg every two weeks
The third cohort could have gotten either one of those doses, but [in] a very important subgroup of patients who already had prior T cell redirection therapy, meaning patients who had had other CAR Ts and bispecifics
Even though these are 60-100% response rates, we’re still seeing relapses so you still need new agents. The goal of this study was to really look at these three subgroups. I would start with who these patients were. These were patients with heavily-treated disease.
About 60% were high-risk in some way, which is a very high number. That could be defined either by what we call high-risk genetics, so cytogenetics and FISH; high risk because they had myeloma coming out of the marrow, what we call extramedullary disease; or high risk because they had so-called ISS stage 3 disease at the time of study entry.
In this population, with the typical five to six lines of therapy over six to seven years where almost 95% of patients were refractory to daratumumab, 75% were what we call triple-class refractory (proteasome inhibitor, IMiD, and CD38) and 95% of patients were progressing on their last therapy.
In this heavily, heavily treated group, as a single agent drug, we saw [a] 73-74% response rate in both of those schedules that we mentioned. That response rate was maintained in high-risk patients, ISS 3 patients, and patients regardless of lines of therapy, regardless of the number of drugs they were refractory [to].
One group who had [a] slightly lower response rate was those with extramedullary disease and even those had a 50% response rate, which I think is outstanding. I think safety is also equally important and distinguishes this from some of the other drugs.
What makes alnuctamab different from other bispecifics?
Jack: Dr. Wong, you presented on a bispecific called alnuctamab from Bristol Myers Squibb. Can you share the results of this trial and what might make alnuctamab different from other bispecifics?
Dr. Wong: We presented both the updated follow-up on the intravenous alnuctamab cohort as well as the subcutaneous alnuctamab cohort. The intravenous cohort was actually presented initially in ASH 2019 so there’s been quite some time that’s elapsed.
Basically, the take-home message with the IV alnuctamab was that even though the response rates initially looked exciting, when we got to target doses of 10 mg, there was a lot of high-grade cytokine release syndrome. People got really sick from CRS and one person actually died from it so it was not really optimal in terms of the side effects. Obviously, we don’t want people to get sick from these treatments.
Patients that were on the intravenous alnuctamab responded for a really long time so we’re really, really excited about that. However, we had to pivot to the subcutaneous alnuctamab because of those safety concerns. With the subcutaneous alnuctamab, the overall response rate was at 65%, which is very much in line with other T-cell engagers.
In terms of safety, all the CRS events were very low-grade. They were short-lived. They’re what we call grades 1 to 2 and, in terms of safety profile, it was a lot more manageable compared to intravenous alnuctamab.
That was what was really exciting about our presentation. Not only is subcutaneous obviously more convenient for patients, but the CRS events were much easier to handle and the overall response rate was 65%.
How does this stand out from the other T cell engagers? Several things. This is not the only subcutaneous BCMA-directed T cell engager, but there are some that are intravenous. For example, ABBV-383 is intravenous. So this is great that this is subcutaneous.
It’s hard to compare apples to oranges because all these different BCMA-directed T cell engagers have different follow-up time frames. For this one, the follow-up was very, very short. The median [was] only around four months.
In terms of infectious events, in terms of opportunistic infections, we really haven’t seen much of that for this particular drug so maybe that eventually will pan out longer follow-up studies but unclear because follow-up is pretty short.
What is really exciting is that the MRD negativity was 80% despite these patients [not being] followed for that long. That is actually really exciting. We don’t have a signal for these high-grade infections or opportunistic infections though. Again, follow-up is pretty short with this drug.
What are common side effects for bispecifics?
Jack: Speaking of infections, what are the common side effects we’re seeing with bispecifics altogether? I understand some research is unearthing data about how myeloma patients on certain drugs do with COVID and the vaccine.
Dr. Chari: I’ll start with what’s the most severe toxicity and then we’ll go to what’s common because I think they’re different and they’re both equally important to address. From a patient perspective, if it’s severe but rare, you may not be as concerned, but if it’s common and frequent, that’s different.
The most severe side effect is low blood counts. We see that in about a third of patients with this drug. Typically, it happens in the first few cycles.
My personal hypothesis, I think what’s happening is when the army is going to the marrow where a lot of myeloma lives, you kill the myeloma but you may temporarily also affect the rest of the marrow. Then once the myeloma clears, you see that [improvement].
Jack: Patients may hear that called cytopenia. Is that correct?
Dr. Chari: Correct. That’s exactly right. It could be the white cells, the red cells, or the platelets. Those are important. This is already a little bit less than some of the other drugs, which can have as high as 60%. This is about half of that.
The second huge thing, which you alluded to and it’s very important, is the infection. I can tell you, being in New York City [during] the pandemic, this was really a difficult situation. We had patients on experimental therapies and we were facing these life-threatening COVID decisions every day. We didn’t know what to do with this setting.
I think the infection profile of talquetamab is very unique. I’ll give you three ways why I think it differs from some of the other products.
First, the rate of severe infections was about 10-15%. We want it to be zero, but to put that into context, some of the other drugs are 45%.
We’re not just talking [about] minor infections, which can be seen with any myeloma patient because of the nature of the disease. [These are] severe, life-threatening infections, what we call grade 3-4. That was relatively modest.
Second, the COVID signal is very different with this agent. Talquetamab as well as a lot of the other bispecifics are all accruing during the era of COVID. Yet in the phase 1 study that was published in [the] New England Journal with about 250 patients, there were zero COVID-related deaths.
In this study, there were two COVID-related deaths despite 10% of the patients having COVID. That’s a unique signal. In fact, in our laboratory at Mount Sinai, when we’ve tested people getting talquetamab [and] their response to the COVID vaccine, they do very well. They’re able to generate antibodies, which we don’t see with some of the other bispecifics because of the nature, I believe, of the target.
The third and final difference between this drug and some of the other bispecifics is the need for infection-prevention treatments. Is there anything we can do to reduce infection? There is IVIG, which is intravenous immunoglobulin, that’s an intravenous infusion given once a month to boost IgG levels. Here, only about 10% of patients needed IVIG.
All of those features of this drug are very unique. Some of the other products are having as high [a] rate [as] 40% of patients needing IVIG. I think this bodes well because these are probably the two most important features, which [are] cytopenia, blood count, and infections in terms of how these drugs are used in the future.
The ability to combine drugs depends on each agent’s side effect profile. Because infections and blood count issues are quite common, that can make some of these bispecifics difficult to combine. I think, in contrast, that bodes well for talquetamab.
There are some issues with talquetamab that are common but typically low-grade. One you’ve alluded to is cytokine release.
I would say as a class, all the bispecifics have cytokine release syndrome on the order of 70% or so, typically low-grade. In contrast, some of the CAR Ts have a little bit higher, more severe cytokine release.
What is cytokine release? It’s when the army recognizes the cancer. The T cells release their chemicals and those chemicals can cause symptoms such as fever, low blood pressure, low oxygen, confusion, lethargy, seizures, and even death, in rare cases. With bispecifics, it’s generally very low-grade. Most of the patients are getting a fever.
Everybody eventually would love to be able to use these drugs [in] an outpatient setting… If we’re able to do this safely as an outpatient, that would be really a big game changer for patients and their quality of [life].
Dr. Sandy Wong
Lowering cytokine release syndrome with treatments
Jack: There’s a big focus on lowering cytokine release syndrome with treatments like bispecifics. In particular, I saw one trial which looked at trying to reduce CRS by giving tocilizumab ahead of time. I’ve seen things like step-up dosing to reduce side effects. I know doctors have asked for possible pre-treatments for reducing infections. Can you share more about this?
Dr. Wong: Everybody eventually would love to be able to use these drugs [in] an outpatient setting. Nobody wants to be admitted to the hospital for a week just to get started on these drugs. If we’re able to do this safely as an outpatient, that would be really a big game changer for patients and their quality of [life].
Dr. Chari: We have to keep in mind one of the very things that’s going to make bispecifics different than CAR T.
CAR Ts are done at transplant centers and specialized large academic centers. These are off-the-shelf products that we hope eventually can get to the community because we recognize that most myeloma patients are not being treated in the global setting and academic centers. They’re being treated by community doctors.
If we want to get these drugs out to the community, we have to make them as safe as possible. How do we reduce that 70% cytokine release? One is by giving tocilizumab. In one of the studies with a bispecific known as cevostamab, [the] rate of cytokine release dropped from 70-80% to about 30%. That’s very encouraging.
The other way to do that, which you mentioned, is don’t throw the whole army at the disease at once. Gradually increase the doses so that if there is some chemical release, it’s not all at once. That creates a lot of drama. You start with a low dose and you gradually work your way up.
Both strategies are being done. With talquetamab, we did do preventative tocilizumab, which is the anti-IL-6 antibody, which blocks the fever. We were allowed to give it when patients had cytokine release, but we didn’t give it preventatively, which is what was presented at ASH [2022] in that one study.
The other side effects [of] this drug are three things. One could ask, “Why is this one different than other drugs in terms of why potentially the infection was better? Why were the blood count issues perhaps not as bad?” We think it has to do with the target.
The target is GPRC5D, which is basically a protein that is expressed on myeloma cells primarily. We think [it’s expressed] less so [in] normal plasma cells and even less so in the normal hematopoietic compartment, which is the precursor cells that give rise to our blood counts.
Perhaps the specificity of this protein is what underlies the favorable blood count and cytopenia issues, as well as the infection profile. There are a few tissues that do express GPRC5D and, fortunately, it’s not the major organs. We didn’t see [the] heart, lung, liver, [and] kidney. Those organs were not affected.
The main thing we did see is GPRCs expressed on heavily keratinized tissue. Keratin [is] in the skin, nails, hair, etc. We didn’t see a lot of hair loss, but we did see some rashes in the early part of the treatment, which [is] typically managed with either oral or topical steroids.
We did see some nail changes and taste changes. We saw dryness, difficulty swallowing, [and] change of taste. That, I think, is the most difficult to manage. We’ve tried artificial saliva and other things.
In spite of everything, the one signal that you can look at to see the tolerability of a drug is how many people came off for non-progression. This was 5%, which means that we were able to manage the side effects to keep people on the drug. I still think we need to do better.
We have to keep in mind that the side effect profile that a heavily treated population might accept is going to be different than the side effect profile of maybe somebody who’s only had one line of therapy.
The good news is that we do think these side effects are responsive to modulating the dose and intensity, so either dropping the dose or skipping a dose, giving it less frequently. Those seem to help. I think that’s why the rate of discontinuation was relatively low.
Again, a huge shout-out to the nurses because they’re really on the front lines and helping patients deal with these side effects. I never take my entire outstanding, talented nursing colleagues for granted. They’re really doing an amazing job. Those are basically, I think, the main side effects to cover with talquetamab as well as most bispecifics, I would say.
We have to keep in mind that the side effect profile that a heavily treated population might accept is going to be different than the side effect profile of maybe somebody who’s only had one line of therapy.
Dr. Chari
Managing side effects for bispecifics
Jack: Let’s summarize the side effect profiles for these bispecifics. I would stay on bispecifics typically until they stop working. I take them every two or three weeks, depending on how they’re dosed. Do these side effects change? Are they worse at the beginning? Whatever side effect I get at the beginning, [does it] continue as I’m taking the drug?
Dr. Chari: There [are] three major bispecific targets that are being explored. We’ve talked about GPRC5D with talquetamab. There’s actually a second company also pursuing that. That was also presented at ASH [2022] from Roche, targeting GPRC5D.
The BCMA is a very busy space. I think it’s like the statins of myeloma, like Crestor [and] Lipitor. It’s great for patients because more competition means more choice [and a] better cost profile. I think it’s great for the market.
I would say the BCMAs seem to keep having a rate of infection that we don’t see a plateau in. That’s what’s concerning to a lot of us. How do we find the right dose, schedule, and duration?
It’s one thing to have an infection in somebody whose myeloma is uncontrolled because that we’ve seen before. Myeloma patients whose myeloma is uncontrolled will get infections because that’s part of the cancer.
What can be sometimes difficult to tease apart in these single-arm studies is you can’t isolate what’s coming from the patients (like if the patient is a very sick patient), what’s coming from the disease of the myeloma itself, and what’s coming from the treatment because you don’t have a control arm in which to compare it to.
One of the things, as your question astutely asked, is there any change? With the infections, we’re not seeing that level off with the BCMA. With talquetamab, we’re not seeing it as much.
I would say with the cevostamab, it’s probably somewhere in between. That’s targeting another protein called FcRH5. I would say [with] infections, we haven’t found the right magic sauce yet. Perhaps IVIG.
One other interesting paper that I think speaks to this topic is Genentech/Roche, the same company that did the prophylactic or preventative toci (tocilizumab) also happens to have the only bispecific that is a fixed duration. They don’t treat the progression. They treat for about a year.
What we saw is there’s a small number, but about 17 patients that had come off the therapy and were in longer follow-up on that study. What we know so far is of the patients that had a deep remission, they’ve been doing pretty well off therapy. Again, [that’s] amazing for patients to have a treatment-free interval.
With talquetamab, we’re not seeing that relentless increase in infection — and to the opposite, the side effects [with] skin, nails, and taste actually seem to get better with time. There may not be as much of a need to do the fixed duration there. Maybe it’s once-a-month dosing or something.
We’re pursuing all of these different strategies, but I would say that we’ve got to look at everything. We’ve got to look at the dose, the frequency, [and] the duration of treatment and figure [it] out for a given patient, based on a given target and on their response.
That cevostamab data, which [was] discontinued for those patients that were not in a complete response, did have [an] earlier relapse.
I think you can’t have a blanket statement. You just got to look at each patient as an individual. It’s nice to have these options that are giving such outstanding responses.
Bispecifics are here. It’s a dawn of a new era… We have multiple drugs against multiple targets that are showing impressive response rates.
Dr. Wong
Next steps for research
Jack: Thank you so much. I’ve learned a lot about bispecifics. I can also tell there’s still a lot of work to do to understand the dosing, to understand if there will be prophylactics that go along with them to minimize those side effects, to see if fixed duration or use till progression will be the right treatment, or just to reduce the dosing going forward.
I still go back to what you said earlier that we’re seeing response rates so high for just this drug, not even combined with something else, and for patients that have already gone through lots of prior treatment lines. It’s certainly an exciting field.
Dr. Chari: Not only are we seeing these responses, [but] the median time to response is one month and the median time to best response is two months. I mentioned those points because it gives us, as physicians, a lot more comfort in backing off on the dose and schedule.
You’re seeing the response early and it’s deep. If somebody has side effects, you’re not as worried about backing off. That’s what’s really nice about these drugs. Even if somebody does have side effects, it’s very gratifying to them to have this myeloma that was shooting off and suddenly it’s completely flattened out. That’s why I think the side effect profile we’ve got to do more work on.
What are the next steps? All the phase 1 and phase 2 single-arm studies have confirmatory randomized studies where the drug’s being combined with different backbone agents.
Also, because of the unique side effect profile, talquetamab in particular is also being combined with all those standard myeloma drugs in single-arm studies as well as with the other bispecific, which is really cool. Completely chemo-free teclistamab with talquetamab is being studied.
Lastly, we’re trying to also improve the T cell function because we think one of the reasons the drugs may peter out is because of T cell health. There [are] approaches using things like checkpoint inhibitors, which boost your T-cell function, in combination with these agents.
Bispecifics are going to be a fabulous treatment option for myeloma patients… I’m excited to see what comes next in myeloma.
Jack
Final takeaways
Jack: Doctors, as we wrap up this discussion on the latest in myeloma, specifically bispecifics, what are your thoughts on where we are in myeloma treatment and research? What’s your message to myeloma patients and families in 2023?
Dr. Wong: Bispecifics are here. It’s a dawn of a new era because finally, we have [an] off-the-shelf drug, which means that you can just take it right off the shelf and just give it to a patient. And for an off-the-shelf drug to have a response rate of 60 to 70%? That is absolutely amazing.
Previous to this, dara (daratumumab) was our darling drug. We use it so common nowadays in the front-line setting and the relapse setting. When dara was FDA-approved, the single-agent response rate in patients who are relapsed/refractory was only around 30%. Right now, we’re hitting 60 to 70% so this is extraordinary.
And it’s not just one drug. We have multiple drugs against multiple targets that are showing impressive response rates. I think really good news this ASH. I’m really excited to see all that amazing data being presented.
Dr. Chari: I think it’s a really exciting future. We’re just in the beginning and, of course, in less heavily treated patients, it’s also a big area of investigation in addition to combination. Stay tuned for all of those exciting new studies, hopefully soon.
Jack: Bispecifics are going to be a fabulous treatment option for myeloma patients. Thank you so much, Dr. Chari and Dr. Wong, for your presentations, [for] helping us better understand bispecifics, and [for] being part of this conversation.
I hope you took away something helpful and hopeful from this conversation. I’m excited to see what comes next in myeloma.
Special thanks again to Janssen Oncology & AbbVie for their support of our independent patient education content. The Patient Story retains full editorial control.
Symptom: None; found through blood tests Treatments: Total Therapy Four, carfilzomib + pomalidomide, daratumumab + lenalidomide, CAR T-cell therapy, selinexor-carfilzomib
