Follicular Lymphoma Patient Expert Q&A: Dr. Brad Kahl
Dr. Brad Kahl from Washington University School of Medicine explores the transformative potential of emerging therapies for follicular lymphoma and their significance for patients and families. He also addresses the unique challenges of living with follicular lymphoma and its impact on patients’ lives today.
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Transcript:
Lisa Hatfield:
Welcome to this START HERE Patient Empowerment Network program. This program bridges the expert and patient voice, enabling patients and care partners to feel comfortable asking questions of their health care team. Joining me today is hematologist-oncologist Dr. Brad Kahl, Professor of Medicine in the Division of Oncology at the Washington University School of Medicine and Director of the lymphoma program at the Alvin J. Siteman Cancer Center in St. Louis, Missouri. Thank you so much for joining us, Dr. Kahl.
Dr. Brad Kahl:
It’s a pleasure. Thanks for having me, Lisa.
Lisa Hatfield:
The world is complicated, but understanding your follicular lymphoma diagnosis and treatment options along your journey doesn’t have to be. The goal of Start Here is to create actionable pathways for getting the most out of your follicular lymphoma treatment and survivorship. No matter where you are on your journey, this program is designed to provide easy to understand, reliable, and digestible information to help you make informed decisions. And most of all, we’re asking questions from you. I’m thrilled you’ve joined us.
Please remember to download the program resource guide via the QR code. There is great information there that will be useful during this program and after. Let’s start here. Dr. Kahl, there is a great deal going on in the follicular lymphoma landscape, and I want to dig into that. But before we do, as is custom for this program, I’d like to start with a brief overview of this disease. What is follicular lymphoma? And can you break it down a little bit, the key differences between Hodgkin and non-Hodgkin lymphoma and how follicular lymphoma fits into that?
Dr. Brad Kahl:
Sure. The terminology can be kind of confusing to patients, so I’ll try to explain it. Hodgkin lymphoma is a specific kind of lymphoma. Non-Hodgkin’s lymphoma just means it’s not Hodgkin’s. So non-Hodgkin’s lymphoma is just a big, broad, descriptive term. It’s like saying automobile. But there are lots of different kinds of cars, obviously. So follicular lymphoma is a specific type of non-Hodgkin’s lymphoma. So it’d be like saying Chevy Malibu or something specific within that automobile term. So there’s like 100 different kinds of non-Hodgkin lymphoma. Follicular lymphoma is one of those. A
nd it’s kind of a unique answer biologically and clinically. Follicular lymphoma is characterized by this particular mutation inside the cells that sends a signal to the cells that says don’t die. So instead of being a disease of rapid cellular proliferation and growth, it’s more of a disease of slow cellular accumulation. If people can picture that, the cells are just accumulating slowly. So it’s kind of a slow-moving cancer. And probably when patients are diagnosed, they’ve probably had it for a long time already.
They just didn’t know it, because follicular lymphoma often doesn’t cause symptoms. And usually when we get a patient with newly diagnosed follicular lymphoma, the disease is very widespread. And that obviously makes people fearful. And so we spend a lot of time trying to reassure them that’s not a problem that’s typical for follicular lymphoma. Everybody wants to know their stage, of course. And I try to tell them, the stage doesn’t really matter that much in follicular lymphoma. In some cancers, the stage is a big deal. But those are cancers that you can kind of remove surgically.
But there’s really no role for surgery as a treatment in follicular lymphoma. The disease is typically very widespread in diagnosis, meaning it’s all over the body. And so when we do treat it, we pick treatments that will work everywhere. And our treatments tend to work just as well when the disease is at a more advanced stage. That’s why as the doctors, we don’t spend too much time worrying about the stage. It’s just not, it’s not as important in follicular lymphoma.
Lisa Hatfield:
Okay. Thank you. And just to clarify, when you mentioned that there is a mutation or often mutations in follicular lymphoma, is that in the cancer cells themselves, or is that in a mutation, like a BRCA mutation that a patient can be tested for? I presume it is.
Dr. Brad Kahl:
Right. That’s a great question. The mutation is specific to the cancer cells. So people are not born with this mutation. It’s not a mutation that you pass along in your family to children. It’s a mutation that is acquired in these cells at some point in the patient’s lifetime. Another confusing term is this whole idea of B-cell lymphoma or T-cell lymphoma.
And just to try to clarify that. So we have different kinds of lymphocytes in our body, and these lymphocytes, they have jobs to do as part of our immune system. And one kind of lymphocyte is a T cell, and that has specific roles in our immune system. And another kind is a B cell, and that has specific jobs to do in our immune system. Follicular lymphoma is derived from a B cell, a B-cell lymphocyte. So the…a B cell gets this mutation, and that turns it from a normal healthy B cell into a follicular lymphoma cell.
Lisa Hatfield:
Okay. Thank you for explaining that and for that overview. That’s really helpful. I appreciate that. So, Dr. Kahl, you also mentioned treatments and how oftentimes it’s not a cancer where you can just remove the cancer. Can you talk about some of the exciting developments with treatments and new innovative therapies, and what are the most important highlights for patients and families?
Dr. Brad Kahl:
Yeah. There’s a lot to talk about here. So I’ll start with how we approach a newly diagnosed patient, and then we’ll go into how we approach patients who have relapsed disease. So the most often, or the most common way a follicular lymphoma patient comes to medical attention is they just either notice a lump from an enlarging lymph node, or some enlarged lymph nodes are just found incidentally because they’re having some testing for some other condition.
And so, like I said, very often patients don’t have symptoms. That’s very typical. Occasionally, the patients will have symptoms, and those symptoms might be pain from a large lymph node mass that’s pushing on something. Occasionally, they might have fevers or night sweats. They wake up in the middle of the night just drenching wet, or unexplained weight loss. Those would be symptoms that can occur in follicular lymphoma. But most patients who come to see us for the first time don’t have symptoms.
When we have a newly diagnosed patient and it takes a biopsy to make the diagnosis, we then need to do the staging evaluation. So that involves some sort of imaging. And nowadays that’s usually in the form of what’s called a PET scan, which gives us a good snapshot of the whole body. And it’ll show us enlarged lymph nodes. And then the PET portion of the scan will show us if the lymph nodes are metabolically more active.
So they show up as these bright spots on the PET scan. And that’s what allows us to stage the patient. It tells us where the disease is located and how much of the disease we see. And so I’m often telling patients, I don’t worry so much about the stage. I worry more about the disease burden. So the way I explain that to patient is, suppose I could take all the follicular lymphoma cells out of your body, and I made a pile. How big is the pile? And that’s actually, I think, more important than the stage in determining our initial strategy.
Because believe it or not, if we have a patient who comes to us with a new diagnosis of follicular lymphoma and they have no symptoms, and it turns out that their tumor burden is very low, we often will recommend an initial approach of no treatment, which is a strange thing for patients to hear. And we spend a lot of time trying to explain the rationale for that. So I’ll try to explain that to you now. Follicular lymphoma is hard to cure.
So it’s this weird cancer in that it’s slow-moving. It often doesn’t make people sick, and we have good treatments for it, but curing it, like making it go away once and for all, proves to be kind of difficult. And studies in the past have shown if you have a patient who has no symptoms and is low tumor burden, that their prognosis is just as good if you leave them alone at the beginning. And many patients will not need any treatment at all for two years, three years, five years. I even have follicular lymphoma patients who I’ve been observing for more than 10 years that have never needed any treatment.
About two out of every 10 patients that are newly diagnosed can go 10 years without needing any treatment. So that’s why we’ll start that strategy for some patients. And that’s psychologically can be difficult for patients. You’re telling me I’ve got a new cancer diagnosis. You’re saying you have good treatments for it. And yet you’re saying you don’t want to use any of those treatments. And so it takes a lot of talking and explaining to try to get people comfortable with that.
Some people never get comfortable with that, I admit it. But some people get very comfortable with it. But it is a very appropriate initial strategy for a low tumor burden asymptomatic person just to observe and get a handle on the pace of the disease. If the disease starts to grow, or if the patient starts to get symptoms, we can start our treatment at that time. And the treatment is going to work just as well as it would have had if we started it last year, or two years ago.
So we feel like we’re putting the patient in no harm, no risk of harm by starting on this strategy of a watch and wait. On the other hand, some patients have high tumor burden, they have a lot of disease, or they have symptoms. And for those patients we need to start them on treatment because the treatment can put them in remission and get them feeling better. Right now, the most common frontline treatment in follicular lymphoma will be a combination of some chemotherapy and some immunotherapy.
The most commonly used regimen in the United States right now is a two drug regimen, a chemotherapy drug called bendamustine (Treanda), and an immunotherapy drug called rituximab (Rituxan). And you give that treatment every 28 days for six months. And it’ll put 90 percent of people into remission. And on average, those remissions last five plus years. And it’s a very, very tolerable treatment. It’s not too bad as far as chemotherapy goes. There’s no, most people don’t lose their hair. They don’t get peripheral neuropathy, that sometimes chemotherapy drugs give.
It’s not too bad for nausea and things like that. I’m not saying it’s easy or it’s fun. It’s none of that. But as far as chemo goes, it’s not too bad. And it’s effective, it is very effective. And I’ve given that treatment and I have people who are still in their first remission 10 years later, so you can get, for some people can get these really long remissions. But the reality is most patients, their disease does come back, they do relapse at some point. And then we have to start talking about what to do for second line treatment or third-line treatments.
And that’s where things have really taken off in follicular lymphoma in the last few years, there are a number of brand new treatment options in play for relapsed follicular lymphoma that are very exciting, and proves that we’re moving away from chemotherapy. We have drugs that are oral, that are, we call them targeted agents, they hit like a molecular pathway inside the cell a lot, and they kill the cells a lot differently than chemotherapy does. And we have a number of new drugs that work through the immune system, and try to attack the lymphoma that way.
So when we have patients who relapse, probably the most commonly used second-line treatment right now is a combination of a drug called lenalidomide (Revlimid), which is a pill that’s used in a few different cancers. It works very well for certain cancers, and it works well in follicular lymphoma. And that’s given with the immunotherapy drug called rituximab. And that was proven in a study to be very effective. About 80 percent of people will respond to the regimen, and that remission on average lasts in the two to three-year range.
So that’s probably the most commonly used second line regimen right now in the U.S. for follicular lymphoma. And then there are a number of treatments that are now available in third-line and beyond that are new within the past, say three, four years. And these newer treatments that I’m about to describe are now being tested as second line treatments and even as first-line treatments.
So it’s possible that some of these treatments I’m about to describe will become in the future, our go to regimens for first line treatment or second line treatment. And we hope they do move up, because that means they’re, it means they’re even better than what we’ve been using. So probably the treatments that we’re most excited about right now in follicular lymphoma are the drugs called bispecific monoclonal antibodies. There are two that are now FDA-approved. One’s called mosunetuzumab-axgb (Lunsumio), and that was approved about a year-and-a-half ago.
And the other one’s called epcoritamab-bysp (Epkinly), and that was approved just a month ago. And basically these drugs are infused or injected under the skin, infused intravenously injected under the skin and their proteins that will literally stick to the lymphoma cells. And when it does that, it kind of coats the cancer cells. And then after these bispecific antibodies coat the tumor cells, they literally will trick the patient’s T cells or healthy T cells to come in and attack the cancer.
So it’s a way of trying to trick the patient’s own immune system to come in and start fighting the cancer. And these two drugs are very promising in the relapse setting. They work about 80 percent of the time to get some kind of response. About 60 percent of the time patients will go into complete remission, which means we can’t find any evidence for the lymphoma on scans. And they’re both so new that I don’t think we have a full understanding of how durable these remissions are going to be right now.
It looks that like about, if you do get a complete remission, that about half of those patients are holding that complete remission at two and three years. But we’re, we don’t know about four years and five years yet because the drugs are too new. And we expect that if, as these drugs move up and are tested in the second-line setting and in the first-line setting, they’ll work even better because the cancer cells tend to be easier to kill in earlier lines of therapy. Other agents that have moved into the relapse follicular lymphoma space would include CAR T-cell therapy.
This is a fairly sophisticated complicated approach where you actually will run the patient’s blood through apheresis machine and you will extract the patient’s T cells and those T cells get genetically modified in a lab and then expanded and then are shipped back to the center and then re-infused back into the patient. So now again, we’re tricking the patient’s T cells into fighting their B-cell lymphoma.
And there are three CAR T products that are now FDA approved for use in follicular lymphoma, and they have very high response rates. With seemingly good durability we’re now getting three and four-year follow-up for these CAR T products with about half of people still in remission. The CAR T products probably have a little more toxicity and a little more risk than the bispecifics. So I think most of us are thinking we would try the bispecifics before CAR T, but there might be certain patients where a CAR T strategy is more appropriate to use before a bispecific.
So we’re very excited to have these tools in our toolbox. It’s always good to have more options. And then I should just mention the small molecule inhibitors. So here’s an example. Just this past year there was approval for a small molecule called zanubrutinib (Brukinsa). It targets an enzyme called BTK or Bruton’s tyrosine kinase. This is a pill really well tolerated. It’s given in a combination with an immunotherapy drug called obinutuzumab (Gazyva). This zanubrutinib-obinutuzumab combination got FDA-approved just this year for recurrent follicular lymphoma.
The results look very good for that. It’s very well-tolerated. There’s another oral agent called tazemetostat (Tazverik), which was approved a couple of years ago. It targets a mutated protein in follicular lymphoma. This is, again, is a pill super well-tolerated, very few side effects. So, there’s just a few examples for you of all the different treatment options we have for follicular lymphoma that has recurred after initial treatment.
And believe it or not, the decision-making can be difficult when you have so many choices and so many good choices, that’s a good problem to have. And I find myself a lot of times spending a lot of time with the patient and their family as we talk through these different options, and we try to think what’s best for them at this point in time, talking through the pros and the cons, how active it is, what side effects do we need to be concerned about. And it’s a lot for patients to digest when you have so many choices. But like I mentioned that’s actually a good problem to have.
Lisa Hatfield:
I think you’re right. There’s a lot of hope in those options. I do have two follow-up questions. One of them is when you talk about lenalidomide or brand name Revlimid, CAR T bispecific antibodies, this new small molecule, are these all quality of life is so important for cancer patients. Are these all limited duration treatments for recurrent disease when there’s a recurrence of the disease or are they long-term treatments for the disease?
Dr. Brad Kahl:
Yeah, really good question. And the answer is different for every agent. So I’ll try to just kind of run through the list. For the CAR T products, the three different CAR T products, it’s like a one-time treatment and then you’re done because the cells that get infused will persist in the patient’s body for months and months and months. So they’re infused and then the cells will hang around a long time acting on the cancer. So for the CAR T it’s a one-time treatment. For the bispecifics, the mosunetuzumab-axgb product is a time-limited treatment that is done in less than a year. The epcoritamab-bysp is designed to be given indefinitely.
So those are, there are some pros and cons of those two agents, the two small molecules that I mentioned, the zanubrutinib is meant to be given indefinitely and the tazemetostat is meant to be given indefinitely. And then the first one I mentioned was the lenalidomide. That is in follicular lymphoma that it was developed to be given for 12 months in this setting. So the duration of therapy is unique for each of the different agents that I mentioned.
Lisa Hatfield:
Okay. Thank you for that overview of all those emerging therapies. That’s great to know for patients, Dr. Kahl. All right. It’s that time where we answer questions we’ve received from you. Remember, as patients, we should always feel empowered to ask our healthcare providers any and all questions we might have about our treatment, our disease, and our prognosis. Please remember, however, this program is not a substitute for medical care. Always consult with your own medical team.
So, Dr. Kahl, we have several patients who have submitted some questions. The first question is regarding emerging technologies. And I think that you probably have answered that very well actually in a discussion here. So the second question this patient had is how might future innovations build on the latest treatments to offer even better outcomes for patients? You, I think maybe have touched on that, but maybe speak to that a little bit more as far as longer remissions. Yeah.
Dr. Brad Kahl:
Right, right. So I think right now the main emphasis in research is to take some of these really promising drugs that were developed for relapsed follicular lymphoma and do two things with them, test them in combinations in the relapse setting to see if you can make them even more active. So an example of that would be take the drug lenalidomide, which is really active in the relapse setting and pair it with the drug mosunetuzumab-axgb, which is very active in the relapse setting, and pair them together and see if you can get better results than either drug alone.
So there are studies trying to answer questions like that at this time. And then the other area of major interest is to take these promising new treatments approved in the relapse setting and test them upfront. So there are studies being literally designed right now as we speak that will test bispecific monoclonal antibodies in the frontline setting.
So patients can envision being offered a chance to have a chemo-free strategy where they’re just getting a bispecific monoclonal antibody as their initial treatment. And there are studies that will test these drugs as single agents, and there are studies that will test these drugs in combinations with other agents in the frontline setting, like lenalidomide, for example. So we have no results from any of these trials yet, but these trials are just starting to enroll patients and this could fundamentally change the way we’re managing follicular lymphoma in the future if any of these new strategies turn out to be more promising than what we have done historically.
Lisa Hatfield:
Thank you. Okay. Another question, Dr. Kahl. How do outcomes differ for patients with relapsed/refractory disease compared to those who respond well to initial treatment?
Dr. Brad Kahl:
So that’s a really good question. And when we have a patient going through frontline treatment, we’re all really crossing our fingers that that first remission is incredibly durable. Because when the disease relapses, the remissions do tend to get shorter and shorter and shorter, which is frustrating for everybody.And so we love it when we get a nice long first remission. And in the older days when all we had to offer was chemotherapy and some different immunochemotherapy regimens, the remissions in second line and third line might be two years or one year. It can get frustrating as you go through treatment after treatment after treatment. It’s hard on patients. The side effects start to accumulate. And that’s one of the reasons we’re so excited about all these new agents that we have for relapsed disease with the bispecifics and the CAR T products and the small molecule inhibitors like tazemetostat and zanubrutinib. Because it appears as though these remissions for relapsed disease might be getting longer than what we have seen historically. So there’s no question that dealing with relapsed follicular lymphoma is more difficult than dealing with frontline follicular lymphoma. But we’re optimistic that these newer treatments we have are improving outcomes for patients with relapsed disease.
Lisa Hatfield:
Okay. Thank you. And another question, which patients are considered the most vulnerable when it comes to follicular lymphoma and why, and what measures can be taken to better support these populations in terms of treatment and care? And I’m not sure if they’re talking about different age groups or ethnic groups or geographic groups like rural versus more urban areas, but if you can speak maybe to general terms to answer that question, that would be great.
Dr. Brad Kahl:
Yeah, right. Well, the first thing that comes to mind are older patients. Older patients are always more challenging to take through cancer therapies. The older patients are more fragile. They don’t tolerate the treatments quite as well. They don’t have the physiologic reserve. They’re more susceptible to complications and infections. So I always think when we have older patients that need treatment in follicular lymphoma, the doctor has to be extra, extra careful, sort of the Goldilocks principle. You don’t want the treatment too hot and you don’t want it too cold, too hot, it might work great, but you might get unacceptable side effects too cold, maybe no side effects, but not enough activity against the disease. So we’re always trying to get that patient the best remission we can get them, but doing the least amount of harm along the way.
So I think that takes a little bit of art, a little bit of experience to figure out how to get your older more fragile patients through follicular lymphoma therapy. And then I think the whole idea of patients who live in rural areas, that can often be challenging too, because they may be hours and hours away from medical care. So if they do have a complication of treatment, an infection, for example, it can be challenging to get them the care they need in a quick amount of time. So when I have patients who I know live way out in the country, far away from our center, I just, we always give them a card, it’s got our phone number and I’m like, you feel like something’s going wrong, call us. I don’t care if it’s 2 in the morning, you call us.
It’s not your job to figure out what’s going wrong. That’s our job. It’s just your job to describe to us what you’re experiencing and then we’ll figure out over the phone whether we want you to drive the three hours to come see us or whether we think you just need to go to the closest place, which might be 30 minutes away. So at least you’re in the hands of some medical professionals. And then they can call us with an update on what they’re noticing, what the tests are saying. So taking care of patients who live far away from the medical center poses some additional challenges.
Lisa Hatfield:
Okay. Thank you. And that’s a great takeaway for patients. If you have a question, call your provider. They can help take the stress away from making that decision yourself.
Well, here’s a loaded question for you, Dr. Kahl. Why does relapse happen in the first place, and what are the changes in the body that signal when and if treatment is likely going to fail?
Dr. Brad Kahl:
Boy, we wish we understood why relapse happens in the first place. Last I mentioned, most of these treatments can get people into remission, which means that they can kill the vast majority of the cancer cells, maybe 99.9 percent of them, but for some patients, there’s just a few stubborn cells that remain behind. Maybe those cells are just sitting there, not growing at all, which follicular lymphoma cells can do.
And when the cells are not trying to divide, not trying to grow, they’re kind of protected from killing. They’re just sitting there doing nothing. And so we think it’s this property that how the cells kind of protect themselves. And so these rare cells that are just kind of sitting there, quiescently not growing, not dividing, these might be the cells then that just hang around for years and then contribute to that relapse five years down the road.
But I admit we don’t fully understand why one patient will relapse two years after a treatment and the next patient is still in remission 10 years later. These are things that we don’t fully understand. Every patient’s lymphoma is a little different, I’m afraid. So two people with follicular lymphoma, they don’t really have the same cancer, cancer, they are sort of like snowflakes. No two are alike. And so they can have different mutations inside the cells that’ll make the cancer behave a little differently from one patient to another. It might make it respond to treatment a little differently from one patient to another. And so what is true for one follicular lymphoma patient may not be true for another.
So if a patient’s symptoms are not being relieved, that might be a clue that the treatment isn’t working as well as we want it to. And then in some cases the only way to figure out if a treatment is working is by scanning. So we’ll have a before picture from a PET scan or a CT scan, and then we’ll take them through a few cycles of treatment, and then we’ll get another scan to prove that the treatment is working like we want it to work. And if it’s not working like we want it to work, then we’ll say, okay, this one isn’t working for you. Let’s go to the what we think is the next best option for you.
Lisa Hatfield:
Okay. Thank you. And just listening to you and hearing about all these nuances with follicular lymphoma, I would probably recommend as a patient myself with a different kind of cancer, seeking out at least a consult from somebody who specializes mostly in follicular lymphoma, at least a hematologist who can tease through some of these nuances to help you as a patient find the best treatments and therapies and quality of life. So just a little tidbit there. So, Dr. Kahl, thank you so much for being part of this Patient Empowerment Network START HERE program.It’s these conversations that help patients truly empower themselves along their treatment journey. And on behalf of patients like myself and those watching, thank you for joining us, Dr. Kahl.
Dr. Brad Kahl:
Thank you for having me.
Lisa Hatfield:
I’m Lisa Hatfield, thank you for joining this Patient Empowerment Network program.
