Follicular Lymphoma Expert Q&A: Coping with Relapse and Managing Treatment Side Effects
Follicular lymphoma expert Dr. Kami Maddocks from The Ohio State University Comprehensive Cancer Center empowers patients and families with practical guidance on key aspects of managing follicular lymphoma. Dr. Maddocks covers effective strategies for managing treatment side effects, navigating the challenges of relapsed or refractory disease, and defining what survivorship means for both patients and their care partners.
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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 healthcare team. I’m Lisa Hatfield, a cancer survivor and also an Empowerment Lead at Patient Empowerment Network. Joining me today is hematologist-oncologist
Dr. Kami Maddocks, Professor of Clinical Internal Medicine in the Division of Hematology at The Ohio State University Wexner Medical Center. Dr. Maddocks specializes in treating patients with B-cell malignancies, including non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, and chronic lymphocytic leukemia. Dr. Maddocks researches new therapies for these hematologic malignancies, largely through evaluating new targeted therapies in clinical trials. Thank you so much for joining us, Dr. Maddocks.
Dr. Kami Maddocks:
Thank you, Lisa. It’s a real pleasure to be here with everyone today and talking about follicular lymphoma, and I just really appreciate you having me.
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. Joining us are patients and care partners facing a follicular lymphoma diagnosis, some of which are newly diagnosed, in active treatment, watch and wait, and also living for years with their disease.
START HERE is designed to provide easy-to-understand, reliable, and digestible information to help you make informed decisions. 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. Okay, Dr. Maddocks, let’s start here. What is the latest in follicular lymphoma, and what are the most important highlights for patients and families?
Dr. Kami Maddocks:
When we look at some of the stuff that’s changed in follicular lymphoma, there has actually been some really exciting developments just in the last year in follicular lymphoma. So when you look at patients who have relapsed or refractory follicular lymphoma, we’ve actually seen the approval of three different new therapies just in the last year for relapsed/refractory follicular lymphoma. So one of those therapies, we saw a brand new approval, and that’s a therapy which combines an oral targeted therapy with a monoclonal antibody.
So the combination of the CD20 antibody, obinutuzumab (Gazyva), in combination with the BTK inhibitor zanubrutinib (Brukinsa) was approved in March of 2024 for patients with relapsed/refractory follicular lymphoma. And this was based on a study that compared that to the single agent anti-CD20 antibody. So while we have had CD20 antibodies approved in both original treatment for follicular lymphoma and relapsed disease, it was the first time that we’ve had a BTK inhibitor approved for the treatment of relapsed/refractory follicular lymphoma.
In May of 2024, we saw the approval of actually the third chimeric antigen receptor T cell or CAR T-cell therapy for relapsed/refractory follicular lymphoma. So previously, we’ve had two different CAR Ts that target the same antigen or protein CD19 on the cell. And the third therapy with the same target was approved in May of this year for relapsed/refractory follicular lymphoma. And then in June of 2024, we actually saw the approval of the second bispecific antibody for the treatment of relapsed and refractory follicular lymphoma.
So previously, we had one approved almost two years ago in December, and a second one, epcoritamab-bysp (Epkinly) was approved in June of this year for patients with relapsed/refractory follicular lymphoma. So three different treatments approved in this setting in the last year, which increases the options for patients. It also provides us with thinking about sequencing these agents. And there’s a lot of studies ongoing to decide or to think about what is the best way to sequence therapy, because there’s no right or wrong answer currently in which therapy did you choose and when in patients with relapsed/refractory follicular lymphoma.
And then thinking about managing when we’re choosing these therapies, what are the side effects of these therapies and managing these side effects? Right? Because chemotherapy is often used for patients with initial diagnosis, and there is very specific side effects to chemotherapy and ways to manage those side effects. But when we look at some of these newer therapies, we have to think about the different toxicity profiles that they have and how we manage those toxicities.
So when we’re thinking about the newer therapies, like bispecific antibodies and CAR T-cell therapies, there’s very specific toxicity with those therapies, including cytokine release or CRS. And then something called ICANS, which is immune effector cell-associated neurologic toxicities, which are neuro side effects of these therapies. And so how do we identify and manage those therapies and now even looking at ways to potentially prevent patients from having those specific toxicities.
Lisa Hatfield:
Okay, thank you. So regarding those toxicities, like the ICANS and the CRS, is there a difference in how you treat patients? For example, if a patient might experience those side effects, are they hospitalized for that type of treatment initially, or are all of these new treatments done on an outpatient basis?
Dr. Kami Maddocks:
Yeah, that’s a great question. So the answer can be variable depending on the specific product or the center where the patient’s receiving them, and then even the disease that they’re used in. So let’s just talk about bispecific antibodies to start. So the first bispecific antibody that was approved in follicular lymphoma was mosunetuzumab-axgb (Lunsumio). There’s no required hospitalization to administer that, but there is a recommendation that if patients have signs or symptoms of cytokine release.
So the primary symptom is fever. That’s the number one most common symptom that patients will get and how we define cytokine release. But patients can also have hypoxia or a drop in the oxygen or hypotension and a drop in their blood pressure. So if they have these, it’s generally recommended that they’re admitted for a period of observation to ensure that those toxicities don’t worsen or escalate and that they’re treated if they do.
Which treatment can include ruling out other causes. Some patients may need antibiotics if they have low blood counts and a fever. Some people will need fluids and oxygen. Then sometimes we use steroids like dexamethasone (Decadron) or even cytokine blockers to help manage those side effects, particularly if they’re what we call higher grade or more significant. The second bispecific antibody epcoritamab-bysp. That was previously approved in diffuse large B-cell lymphoma and there was a recommended hospitalization with a step-up dosing for that.
However, in follicular lymphoma, when they studied that, they gave an extra dose. So part of trying to prevent the cytokine release is giving a lower dose and then increasing the dose each week until you reach the maximum dose. So they added an extra kind of intermediate dosing in the follicular dosing and showed that that made a lower risk of…a lower number of patients had cytokine release. And that the majority of them had the lowest grade cytokine release.
So in follicular lymphoma, it’s actually with that increased one dose in there to get to the maximum dose. It’s actually not recommended, or it’s not required that patients are hospitalized for any of the doses. But, of course, if they would, same thing, if they would have side effects, then you would consider that. And then the same thing could be said for the CAR T-cell therapies. Some of them are given inpatient and then patients are monitored for a period of time, and then some are administered as an outpatient. And patients are seen daily for that to check on how they’re doing, monitor for side effects, have labs. And sometimes it just depends on the center administering the therapy, how they have a setup for patients to be monitored.
Lisa Hatfield:
So I have two follow-up questions to that overview. Are these newer approved therapies, are they available at some of the smaller cancer centers, or are they only available right now at the larger cancer centers or academic centers? Then my second question is, are they limited duration therapies or like bispecific antibodies, does that just continue until disease progression?
Dr. Kami Maddocks:
Yeah, those are great questions. So in general, if you look at the combination of the obinutuzumab and zanubrutinib that should be able to be administered anywhere, the therapy for the oral therapy is continued until progression. If you look at the bispecific antibodies, there’s both. There’s a time-limited therapy, and then there’s one continued until progression. I think in general, we’ve seen that initially these have been used at larger treatment centers, but now that they’ve been approved for a while, we have seen a lot of these being used at smaller cancer centers and in the community centers. Sometimes patients may receive their initial dosing at a larger center and then transition to a local center. But I think, like I said, now, especially the one that’s been approved for a while, we’re seeing that it can be started at many places.
Lisa Hatfield:
Thank you so much for that important overview, Dr. Maddocks. 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 and prognosis. Please remember, however, this program is not a substitute for medical care. Always consult with your own medical team. So before we dive into this Q&A, since this program centers on coping with relapse and managing treatment side effects, how do you approach these first-time conversations with patients and their care partners who are facing relapse and potentially dealing with a new set of side effects due to the changes in their treatment regimen?
Dr. Kami Maddocks:
I think that’s a great question, and I think there are a lot of things to consider. So I think the first thing that we want to think about when we’re talking about patients having relapsed or refractory follicular lymphoma is that just because patients have relapsed or refractory follicular lymphoma doesn’t always mean that they need treatment. So many patients, when they’re initially diagnosed with follicular lymphoma, are going to go through a period of observation or watch and wait where we know that they have follicular lymphoma, but they don’t have symptoms of their disease.
They don’t have a large number of lymph nodes involved, or their lymph nodes are not very large by the scans, and they don’t necessarily need to be treated until they become symptomatic or have certain concerns from their lymphoma that’s causing problems. So the same thing can happen probably more with relapse than necessarily refractory disease, but patients may…you may detect on scans that they have lymph nodes that are growing or that their disease has recurred, but they don’t always necessarily need to receive treatment.
Once you’ve identified that, yes, a patient requires treatment for their relapsed or refractory follicular lymphoma, the next thing to think about is that patient and their disease. So what age is the patient? What were they treated with initially? Because not all patients receive the same initial therapy. So the decision about what they’re going to receive when they relapse is going to be somewhat dependent on what they received for their initial therapy, what side effects they had from that therapy, and how they responded to that therapy.
The next thing is going to be that there is not just one option at relapse so really discussing the different options for those specific patients, and what are the options, what are the side effects of those options, what is the treatment schedule of those options? Because some treatments may have more toxicity, but they’re time-limited, whereas other therapies may be continued to help progression, they may have less toxicity, but over time that’s a toxicity that patients continue to experience on a daily basis.
So really talking to the patient about the options, what does the schedule of that treatment look like? Do they have to come in weekly? Do they have to come in once a month? And then again, the side effects and how that fits into side effects that they had with their initial therapy, how they tolerate that, are any of those side effects still there? For example, if a patient has neuropathy from their therapy, that might be something that lasts and then considering all those things and making an informed decision with the patient.
Lisa Hatfield:
Okay, thank you. And these questions are in the perfect order, because we have a question from Lauren asking you, what is the difference between relapsed and refractory?
Dr. Kami Maddocks:
Okay, this is another great question. I’m sure all these questions are great. When we think of relapsed disease, we think of a patient who’s had therapy, got in a response to that therapy, that response has lasted some time, and then their disease recurs. When we think of refractory, we think of that more as patients that have received a therapy, and they haven’t responded. Now, there is no standard definition of refractory. So we all agree that if a patient gets a treatment and their disease does not respond to that treatment, they’re refractory to that treatment.
But there’s no defined time for which if a patient has a treatment and responds to that treatment but has a short relapse, what’s really considered refractory. In general, a lot of studies that look at a therapy say that if you’ve had it, like if you’ve had rituximab (Rituxan) and you’ve relapsed within a six-month time frame, that that’s refractory. But some studies use three months instead of six months.
Lisa Hatfield:
Okay, thank you. Another patient, Jeff, is asking, Dr. Maddocks, I’m currently in an observation stage of non-Hodgkin lymphoma. I get blood work twice a year and scans once a year. I’m hoping it stays slow-growing. How long on average can a person live in observation mode before treatment must occur?
Dr. Kami Maddocks:
So this is another great question. And I’m going to provide kind of an overview that we’ll kind of set up, because there may be more questions like this. But in general follicular lymphoma is not one disease, which I’m sure since this is a program focused on relapsed/refractory follicular lymphoma, a lot of patients have heard this and know this. But it’s what we call it’s very heterogeneous, or it can behave very differently in patients, meaning that some patients will have very indolent disease, and then there’s a small portion of patients whose disease will be more aggressive.
We know that when we diagnose patients with follicular lymphoma there are some patients that are diagnosed and require treatment pretty quickly, whereas there are other patients that go many years, many, many years without requiring treatment. Some of that is because of the disease, and some of that is because of how we find a patient’s follicular lymphoma. Some patients, we don’t find it until they present with symptoms. Some patients find their own lymph nodes, and some patients are diagnosed because they have a baseline scan that for a totally different reason, maybe get into a car accident, have scans to make sure nothing’s broken, you find an enlarged lymph node, you biopsy it, and you find this diagnosis.
All that said, there are some studies that have looked at patients who are on observation or watch and wait and looked at treating patients who have what we call low tumor burden, or not a lot of lymph nodes, or not very large lymph nodes, but have what’s called advanced stage disease. So lymph nodes on both sides of the diaphragm, not large enough to necessarily require more aggressive treatment, they don’t have symptoms. But we’ve treated, we’ve looked at studies treating those patients with observation or watch and wait or single agent rituximab (Rituxan) therapy. And when you look at the patients in those trials, the median time to needing treatment for patients from observation was three years.
However, there were 30 percent of patients, so one out of three patients who were still being observed at 10 years without requiring any therapy. So there are patients, that’s almost a third of patients at 10 years who’ve been observed, not required therapy in that population of patients. And certainly I have been practicing for a while where I’ve seen patients, I do have some patients who’ve gone longer than that without needing therapy.
Lisa Hatfield:
Okay, thank you. And there you go, Jeff, we hope that you’re in that third.
Okay, thank you for explaining that. Next question, I’m not sure if it’s Jeff Run or Jeffrey is asking about the most common side effects that are associated with bispecific antibodies, and what precautions can be taken to reduce the risk of infection?
Dr. Kami Maddocks:
Yeah, another great question. There are two different bispecific antibodies that are now approved for relapsed/refractory follicular lymphoma. And I will take this time to also say that some of the exciting ongoing work is looking at those agents in clinical trials, in the frontline setting, in combination with other therapies particularly non chemotherapies.In general, I would say similar side effect profile. The most common side effect between them is the cytokine release or the CRS. So that is the most common side effect. Again, this can be defined in different ways. The most common side effects that you see from that define CRS are fever, hypotension or low blood pressure, hypoxia or low oxygen, shortness of breath, chills, tachycardia or higher heart rate.
We have talked a lot about CRS and what it entails and how it is defined and presents. But management, it depends on what we call grading. So for patients who just, who have a fever, oftentimes, number one, you want to make sure that it is CRS and that there’s not an underlying cause. So ruling out infection or coexisting infection, if a patient is neutropenic or has a low neutrophil count and is at high risk for infection, you may treat them with antibiotics with a fever while you rule out infection.
But oftentimes, if they have a fever, you can manage symptomatically anti-fever medications like acetaminophen (Tylenol). If a patient has worsening CRS and has other symptoms associated with it, such as the hypoxia, low oxygen, or hypotension, low blood pressure, then that’s when we escalate therapy. So one you direct treatment towards that. So if they need fluid, if they need oxygen, but then that’s when you’re thinking about starting medications such as the steroid medication. So we give intravenous dexamethasone, or there are certain cytokine blockers such as tocilizumab (Actemra) that can be given to help treat the side effects of the cytokine release.
Other common side effects or that we’re seeing in more patients in the clinical trials, fatigue, rash, and then infections including upper respiratory infections, and then COVID-19 infection as well. So part of treatment of these side effects is early recognition of the side effects. So patients are monitored closely and that you’re dealing with the side effects to help them from worsening. I think infection prevention is very important with these. So it’s recommended to consider prophylaxis for certain infections. So antiviral medication to prevent viral, such as shingles reactivation, medication to prevent a specific type of pneumonia, PJP pneumonia, and then consideration I think of just making sure that patients are up to date on vaccination. And if patients do have infection while they’re getting treated, potentially delaying treatment or taking a break in order for them to recover from treatment.
Lisa Hatfield:
Okay, thank you. And this person did not give their name but is asking, Dr. Maddocks, I wanted to know how to travel as safely as possible. Is it advisable to get certain vaccines for travel like yellow fever? I plan to travel to Europe via plane and cruise. They say that there’s stage III non-Hodgkin’s follicular lymphoma getting treatment every eight weeks.
Dr. Kami Maddocks:
So this is a great question, and I’m probably going to answer this a little bit more generically, because I think that it can depend a little bit as far as what specific vaccines. But when thinking about travel, I think that it’s a good idea to look at where you’re traveling because both, where you’re traveling time of year you’re traveling and what you’re going to do when you’re somewhere can depend on what vaccines are recommended. I usually advise patients to consider looking at the CDC guidelines for recommendations for what should be received in that area, travel that time of year, what they’re going to be doing.
And then sometimes there are places that will actually have a travel clinic. Once I know what vaccines are recommended, the patient knows what vaccines are recommended, then I usually work with them and pharmacy to decide what vaccines, if they can receive all those vaccines or if there were certain ones that we may not recommend. In general, it can depend on a patient, what treatments they’ve received or if they’re actively receiving treatments. But in general, we like to avoid live virus vaccines in our patients. So I take into all those factors and then would recommend discussing the specifics with your physician.
Lisa Hatfield:
Luca is asking what are the long-term side effects of bispecific antibody treatment, and how will I be monitored for them after treatment ends?
Dr. Kami Maddocks:
So another great question. I think, when we think about the side effects in general, the bispecific antibodies in the CAR T both have those unique toxicity, cytokine release being the most common. And then you also have worry about the neurological toxicity. The difference is that, depending on the specific, bispecific or CAR T that you use, but we usually, typically see these occur in lower grade or not as severe with a bispecific antibody than you can see with a CAR T-cell therapy.
You can still have cytopenias and infection risk with these therapies. Whereas in chemotherapy, we think of that as more generalized toxicities, with the cytopenias, with the risk of infection with the GI toxicities. When we think about long-term side effects, so I think one of the important things to recognize is that bispecific antibodies have not been around that long in the scheme of things, though we can’t say, the risk of 20 years, what do we see or even 10 years.
But when we think about what we have seen, we’ve seen things like the cytokine release, the infections, the cytopenias, but what we haven’t seen is things like the secondary malignancies that we worry about when we think about chemotherapy or even maybe immunomodulatory therapy or secondary cancers that patients can develop. I think for long-term monitoring, right now, at least the biggest thing you want to think about is that these therapies do deplete the lymphocytes, for a prolonged time. And so the risk of viral infections or reactivation of infections, and making sure that’s being considered.
Lisa Hatfield:
Okay, thank you. That’s an important question. So another may possibly be a care partner, Marilyn. How can I best support my loved one during relapse and what should I do if I notice my husband with new or worsening symptoms?
Dr. Kami Maddocks:
So another great question. I think it’s first of all important to ask the physician about what symptoms to watch for. So you know, are there certain worsening new symptoms or worsening symptoms that seem more likely to be related to follicular lymphoma versus something else. I think it’s always important to encourage your loved one if they are experiencing new symptoms to reach out to the physician so that they can be evaluated. Because follicular lymphoma is a disease that many people live with and many people live with it for many years. We know that patients can experience other things.
Not everything is going to be just because of the follicular lymphoma. So it’s important to be evaluated, and recognize what is going on and what is attributed to the follicular lymphoma. I think being supportive, thinking of questions to ask and making sure that those questions are answered. I think thinking about, are there resources available? I think educating yourself is one of the most important things that people can do. So knowledge is power. So just participating in things like this I think can be very helpful, because learning about what’s out there, knowing that there are many options, I think being supportive and having a positive attitude, are all helpful things.
Lisa Hatfield:
Okay, thank you. So we have another big and important question from Aubrey. How can I live a full life with follicular lymphoma while managing the emotional toll of knowing the disease may relapse? And what lifestyle changes or habits should I focus on to maintain my health during remission?
Dr. Kami Maddocks:
Yeah, so this is another great question, and I think there’s probably lots of different ways to answer this or lots of different things to consider. So I think in general, as we’ve talked about follicular lymphoma is something that people live with for a long time. So thinking about just your general health and general disposition. So, we want to think about incorporating exercise, incorporating a healthy lifestyle, thinking about exercise, and being physically active.
Thinking about particularly diet and not saying that there’s any food that you need to avoid or any specific thing, but I think eating healthy is important. I think sleep hygiene is, can be very critical for patients. I think finding, and then just general health, it’s good to have a PCP so that you’re getting good routine health maintenance. We have to think about making sure that we’re managing other medical things like blood pressure, glucose, looking, doing other routine cancer screenings, depending, if somebody’s male or female, but the screening that’s recommended for that.
Now when we’re thinking about managing this does take an emotional toll because a lot of times, when somebody’s initially diagnosed, if they don’t need treatment, the question is always like, well, how long am I, is it going to be before I’m going to need treatment? How am I going to tolerate that treatment? How long is that treatment going to last? And then that resets once a patient’s had treatment. Well, how long will I stay in remission for this treatment? What’s going to be next?
I think things that can help with that are, sometimes I think involving like psychosocial oncology, I think support groups, I think that it’s very beneficial for many patients to talk to people, whether it be through a u look at the median age at diagnosis is in the 60s, and median overall survival is greater than 20 years. So many patients are going to live with this more like a chronic disease. And so learning to kind of knowing basic facts on what it is, what are the treatments that are available, what do those treatments look like, what are the reasons that you need those treatments? And that you are able many times in those periods of not needing treatment to live a very normal lifestyle and do things. I think making sure that, I think it’s important.
One thing that I think can be helpful is you’ll continuously follow up with your physician. So thinking about questions and concerns that you have throughout the period of time, writing them down that gets them out of your mind on paper. And then when you go to see your doctor next, you have that list of questions. Because I think, sometimes we think about things, and then we worry, worry, worry. But putting them down on paper or even sending them through like a secure MyChart email message and then talking them out, because a lot of times if you don’t do that, then when you go to see your physician you think, oh, I don’t really have any questions.
And then you leave and you’re like, oh, I should have asked these 10 different things. So again, I think asking for resources. So there are many different patient friendly resources out there. I think reading material that’s been written or vetted by medical professionals as opposed to just any random material can be very helpful for patients. And then again sometimes seeking out kind of peer support.
Lisa Hatfield:
Okay, great, thank you. Sean is saying that he was diagnosed with follicular lymphoma in 2022 and in an active treatment. What advice do you have for someone transitioning from patient to survivor? I am eager and fearful.
Dr. Kami Maddocks:
Awww. Well, another good question. And I think one thing I want to recognize is that somebody with cancer is defined as a survivor from the time they’re diagnosed moving forward. So you’re already a survivor. But when you, I do think, and I tell patients this, even when we’re talking about starting treatment, I do think that being aware of kind of where patients are at mentally is important.
Because when you go through, when a patient goes through treatment, they’re very focused on next steps and next steps when you’re going through treatment are, when’s my next treatment going to happen? When’s my next scan going to happen? When you get to that point, when you’re done with treatment, you no longer have those small milestones that you’re reaching the next treatment, the next scan. You now are like, oh my gosh, I had this treatment and now, how long is it going to last?
What’s going to happen to me? What else can happen to me? And there can be a lot of fear and anxiety. I would first tell you that’s totally normal. That is a normal feeling to have at this point. So I think one, recognizing that you have them is important. I think considering things like we’ve talked about, is there a survivorship clinic, is there psychosocial oncology? Is there something that might help in talking those things out? I think setting up milestones, what is the next thing? I’m going to have a three-month appointment, I’m going to have labs.
These are the things I need to be thinking about, but if I’m not noticing these also, what things can I do to return to the things I like to do. I think also I would go back to saying, I think this is where just thinking about getting good sleep, getting exercise, eating a healthy, balanced diet, and then socializing and making sure that you’re involving friends and family.
Lisa Hatfield:
Okay. Thank you. And, Sean, you’re already a survivor, Dr. Maddocks said so. So good luck, Sean. All right, Dr. Maddocks, 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. On behalf of patients like myself and those watching, thank you so much for joining us, Dr. Maddocks.
Dr. Kami Maddocks:
Well, Lisa, thank you so much for having me. It’s been a real pleasure, and I hope everybody has a great day.
Lisa Hatfield:
Thank you. I’m Lisa Hatfield. Thank you for joining this Patient Empowerment Network program.
