Dr. Nastoupil:
Welcome to Relapsed/Refractory Follicular Lymphoma: Choosing the Right Regimen for the Right Patient, an ASCO Post roundtable. I'm Dr. Loretta Nastoupil. I'm a community oncologist at Southwest Oncology in Durango, Colorado. Joining me today are two of my colleagues, I'll hand it over first to you, Dr. Casulo.
Dr. Casulo:
Hi, I'm Carla Casulo. I'm from the University of Rochester, and I'm a lymphoma specialist. Thanks for having me.
Dr. Nastoupil:
And Dr. Maddocks.
Dr. Maddocks:
Hi, I'm Kami Maddocks from the Ohio State University. I'm happy to be here.
Dr. Nastoupil:
I really look forward to our conversation today, and we're going to kick this off with our first case. We'll discuss the management of follicular lymphoma after first and early relapse.
So, this is a patient in my practice, he's a 62-year-old male, very fit, he enjoys a lot of physical outdoor activity, including downhill skiing, fly-fishing, and carpentry work. He's also very active in his community, and he has no comorbid conditions. He initially presented in 2023 with peripheral adenopathy, and at the time was otherwise asymptomatic. That prompted imaging, which revealed adenopathy above and below the diaphragm, including in the regions of the axilla, retroperitoneum, the mesentery, and iliac chains. The largest node was 5 x 3 cm, and he had five nodes that were at least 3 cm in size or larger. He undergoes a biopsy of the axillary node revealing low-grade follicular lymphoma, and immunohistochemistry is a typical phenotype positive for CD19, CD20, and CD10, negative for CD5, and translocation 14;18 was present. The Ki-67 was 20%.
He completes his workup with the PET/CT, which again confirms the adenopathy above and below the diaphragm, as well as one extranodal site in the left anterior sixth rib. SUV max was 13. LDH was elevated in terms of chemistries but less than two times the upper limit of normal. And so, just to summarize, this is a fit, 62-year-old man who presents with peripheral adenopathy who is diagnosed with low-grade follicular lymphoma, advanced stage, FLIPI of 4.
So, he receives a front-line regimen of bendamustine and rituximab, and at the end of induction, he has a complete response including resolution of adenopathy. He initiates maintenance rituximab, but that stopped after about 1 year due to pneumonia, and following this, he is under close observation.
So, he's now returning in the spring of 2025. He reaches out to us because he has this progressive cough, and he's concerned that maybe he has a recurrent infection given what he'd experienced about a year prior. So, imaging is pursued, and CT of the chest reveals that he's got bilateral lung nodules. The impression from the case is this could reflect infection, inflammation, or malignancy. Given his history of follicular lymphoma, PET has pursued, and again reveals adenopathy above and below the diaphragm, extranodal involvement as well, including the lung, signs of bone marrow involvement, and subcutaneous tissue, and the SUV max is 11. At this point, he undergoes a core needle biopsy of an inguinal node, because that's the most accessible node, revealing a low-grade follicular lymphoma that's recurred.
So, to summarize this case, we have a 62-year-old fit male, again, no comorbid conditions, he's presenting with symptomatic relapse. He has high disease burden as determined by the PET. He's less than 2 years from completion of induction, about a 1 year remission duration following his last maintenance rituximab dose, and so we'll kick this off. Dr. Casulo, how would you approach this patient, and specifically are there disease or patient specific characteristics that might inform what you do next?
Dr. Casulo:
Yeah, so this is a tough situation. This is a young person with recurrent follicular lymphoma within a short period of time. So, that 2-year time point, which is where you're concerned that the disease biology sort of dictates an adverse outcome. That's the case whether it's transformed disease, which certainly confers a higher risk of lymphoma-related death, but even for patients who have recurrent follicular lymphoma within 2 years, that's an adverse prognostic marker. So, that's a little concerning. So, that's one patient-related aspect that I always think about in terms of selecting treatment. And then, the fact that he has grade 1 to 2 recurrent disease and not transformed, that has an impact on the therapy that we would choose.
So, we have a couple of options for second-line therapy that have now been added to the armamentarium for follicular lymphoma. We used to very commonly use, at least in my practice, lenalidomide and rituximab as an option, based on the AUGMENT study.
Since then, we've had lenalidomide and rituximab as a backbone against which many other phase III combinations have been tested—so would be the doublet approach. Then other potential approaches could be triplet approaches that use lenalidomide and rituximab with the addition of epcoritamab, a bispecific antibody, or lenalidomide and rituximab with tafasitamab, which is CD19-directed antibody. So, those are some of the approaches.
Why that and not chemotherapy? In my opinion, it would be because we've demonstrated that for patients with follicular lymphoma who have early relapse and are treated with chemotherapy, outcomes don't seem to be as favorable as if they were to use something novel. So, I typically use time from initial treatment as the benchmark to decide where to go from there in terms of treatment approaches.
Dr. Nastoupil:
Dr. Maddocks, what are your thoughts?
Dr. Maddocks:
I have very similar thoughts, I guess. Just stepping back, as mentioned, this patient is a higher-risk patient—they fall into that progression of disease within 24 months, or POD24 category, which as mentioned, has a worse prognosis overall. I think what is important to note about this case—and which was done—is that that portion of these patients will have occult transformation and not just progression of follicular lymphoma. So, it is important to biopsy, as was done in this patient. I agree, things that I take into consideration are the patient age and fitness, their comorbidities, and then patient preferences.
I have a very similar approach. I historically used a lenalidomide-based approach in these patients as was described. I would oftentimes, if there was a short time from rituximab-based therapy, consider obinutuzumab in combination with lenalidomide. But as Dr. Casulo mentioned, with the more recent randomized data adding tafasitamab or epcoritamab to the R2 combination would think about one of those options.
Dr. Nastoupil:
I recognize both of you work at large academic centers, at the pulse in terms of what's changing in the world of follicular lymphoma. Now that I'm in community practice, I recognize these are rare tumor types, and often the community oncologists may not be as aware of some of these triplet combinations that have rolled out. What are some particular insights you might be able to share? Because you've both talked about lenalidomide plus rituximab backbone, but with two different sort of partners there: one, an antibody, another a bispecific antibody. And so, how do you navigate that in terms of how do you communicate to your partner in the community on how they might choose between those? What are some sort of practical considerations for how you might administer those therapies?
And maybe again, I want both of your opinions and maybe compare and contrast the differences between those triplet options. Carla, we'll start with you. What are your thoughts?
Dr. Casulo:
They're different, and I think a little bit of that decision making has to do with logistical considerations. They're both very effective combinations, and they haven't been compared one to one, so we can't say one triplet is better than the other triplet. So, you have to use that big picture view of if I have access to both things, which in the U.S. we're fortunate that we do have access to both options, both triplet options. Then there's those logistical considerations of the frequency of visits to the cancer center, which is higher with tafasitamab, the risk of the duration of treatment. Tafasitamab is IV, epcoritamab is subcutaneous.
Whether or not the patient has preserved CD20 on their biopsy has emerged as a really important marker of lack of response to bispecific antibodies. So, let's say that this person—I believe you mentioned that they were low-grade follicular lymphoma and relapse, I'm not sure if they've looked at CD20—but if this person were CD20-negative, you might select tafasitamab instead, just in terms of narrowing down on the biology of that decision making. The other thing is that with a bispecific antibody, there's a big use of prophylactic antimicrobials, steroids, the need to prophylaxis against pneumocystis. Those are some of that infectious consideration is really important too. So, I feel like depending on what the tolerance is for the pill burden, the time to toxicity, the visits to the cancer center, I think that makes a huge impact on quality of life and that goes into the decision making.
Dr. Nastoupil:
Kami, can you share some insights in terms of utilization of tafasitamab in combination with R2?
Dr. Maddocks:
Yeah, so I think a few things to think about are just the difference in the visits. So, for the first 3 cycles, it is a weekly infusion, but then there is less visits with tafasitamab. I think in general, when you look at toxicity considerations that the addition of tafasitamab didn't appear to add as much in terms of toxicity, but there might've been a little bit higher infectious complications when you look at the addition of the bispecific antibody. So, in this particular patient that we're looking at, there was already concern for infectious toxicity with the initial rituximab maintenance. But then of course you can think about different ways to help with prophylaxis and IV/IG, in both situations, to see if that can improve or decrease the risk of infection and improve the outcomes from the toxicity standpoint.
Dr. Nastoupil:
And then are there considerations of just the extent of the disease. Again, I was taken by the fact that he's coming in, he's quite symptomatic. We've seen a lot of follicular lymphoma patients that relapse, and maybe it's an incidental finding on surveillance imaging, or they come in and they're having an exam, and we just pick up on a peripheral node. This is someone who's calling in early saying, "I don't feel well," and imaging shows bilateral lung nodules. He had quite a bit of subcutaneous involvement, marrow involvement. Does that factor into your decision at all? Both of you highlight that we pursued a biopsy just to ensure we've excluded a transformed event, what PET features might help you?
We went after a lymph node that was easily accessible because I have general radiologists performing biopsies for us, and so ease of access is oftentimes a consideration of where we sample these nodes. So, any insights there in terms of how this patient is presenting?
Dr. Casulo:
Yeah, I would say certainly the burden of disease is worrisome. If he had bone marrow involvement, we'd have to take into consideration whether or not that will impact his recovery time, particularly with lenalidomide-based approaches, which we know will cause cytopenias... All of them will, but I think that's another consideration. We have to anticipate if he might need dose reductions or dose delays, so that's another thing to think about. And then, just a big picture view of the biopsy location, it sounds like he had a biopsy that was highly informative, but whenever you have the concern for a higher SUV, there is that risk of transformation. I think that it wouldn't necessarily change the treatment choice for him, but rather would make me worry about the duration of his response, and whether he might rapidly need to go on to another third line of treatment after this.
Dr. Maddocks:
I think the thing that I would add to that is additionally, there are some patients that I biopsy what's easily accessible, and maybe the highest SUV to be easily accessible. But I do, regardless of the biopsy results, take into account the full picture of the patient. So, if they have a very high LDH, if this has happened rapidly, if I think I'm not targeting the right, I will sometimes treat them clinically like there's more transformed disease there.
Dr. Casulo:
Yeah, that's a really good point, Kami, because one of the things that gives me a little bit of peace of mind is knowing that these regimens, at least tafasitamab has activity in large cell lymphoma, epcoritamab has activity in large lymphoma. So, if there is an occult large cell component, I think it may not be the optimal treatment that you'd pick for that person necessarily, but at least you could have some peace of mind knowing that those cells potentially are also being treated.
Dr. Nastoupil:
I really appreciate both of your expertise in sharing where the treatment landscape is evolving, and where we might consider some of these novel therapies that are currently available in that second line setting. And so, just a summary of this first case, the timing of his first relapse was prognostic, he progressed within 2 years of a front-line chemoimmunotherapy regimen, we know that a lot of those cases are enriched for transformed disease. And so, I was very pleased to see both of you were advocating for biopsies to ensure we've excluded transform lymphoma because that's going to potentially be approached differently, and align with our approaches to large cell lymphoma. You've highlighted there are two new triplet combinations that are based off of positive phase III studies that demonstrate either the addition of tafasitamab or epcoritamab on the backbone of lenalidomide, rituximab were superior in comparison to R2.
And both of you shared enthusiasm about the efficacy and the manageable toxicity profile of these agents that we think can potentially be administered even outside of large academic centers. Both of you highlighted on that time to relapse, and how that was a less favorable marker of prognosis, but there aren't as many other risk stratification tools out there, and we have these novel triplets, and maybe you've highlighted some of the key clinical features that might help someone navigate between those two choices, and maybe more research could also help in terms of informing biology or other biomarkers that may help us navigate this.
And we also have to acknowledge that these are patients that are going to face potentially multiple relapses and so considering or balancing that toxicity profile with their goals of care, and our goals for them is equally important. So, this brings us to the end of this case, please see other segments for further discussion about the latest research in follicular lymphoma or visit ascopost.com.
