Dr. Loretta Nastoupil:
Welcome to Relapsed/Refractory Follicular Lymphoma: Choosing the Right Regimen for the Right Patient, an ASCO Post Roundtable. I'm Dr. Loretta Nastoupil, a community oncologist from Southwest Oncology in Durango, Colorado. And joining me today are two of my colleagues. Dr. Casulo?
Dr. Casulo:
Hi, I'm Carla Casulo from the University of Rochester. Thank you so much for having me.
Dr. Nastoupil:
And Dr. Maddocks.
Dr. Maddocks:
Hi, I'm Kami Maddocks from the Ohio State University. It's great to be here with you guys.
Dr. Nastoupil:
In our second case, we'll discuss the management of follicular lymphoma that has relapsed after rituximab monotherapy. So I'm going to jump right into this case.
This is a 72-year-old female. She has some comorbid conditions, including hypertension and controlled type 2 diabetes. She presents with symptomatic normocytic anemia, hemoglobin is 10.5. The other parameters of the CBC are otherwise unremarkable. LDH is normal. A bone marrow biopsy is pursued to investigate the anemia and reveals 25% involvement with follicular lymphoma. It's described as a paratrabecular pattern. VCL2 rearrangement is present.
That prompts further imaging in the form of a PET/CT, which reveals hypermetabolic uptake in the marrow, confirming what we know in terms of marrow involvement, but also some small-volume nodes in the mesentery and the retroperitoneum. The largest is a retroperitoneal node of 2.7 by 2.5 cm and SUV max is 7.4. So this is a 72-year-old, some comorbid conditions, stage IV follicular lymphoma, FLIPI is 3, but technically low tumor burden, but is symptomatic from the anemia.
So after careful discussion about observation vs single-agent rituximab, she opts to proceed with rituximab monotherapy with the goal of improving her symptom burden. And after four weekly doses, she does have resolution of anemia and lymph nodes are now less than 1.6 cm in size. She's feeling better. And so then we have a discussion about observation vs extending out the rituximab in the form of rituximab maintenance, one dose every 2 months for 2 years. And she's in agreement with proceeding with observation.
During a routine follow-up visit, she's now 78, so 6 years have passed. She has mild chronic kidney disease. Creatinine clearance is about 50. She still has hypertension and type 2 diabetes. And now she's reporting that she's more fatigued, her stamina is reduced, and she has a small palpable axillary node. Repeat labs are notable for anemia, and hemoglobin is 9.9. She has mild thrombocytopenia. Platelet count is 120. LDH is currently normal. She's still active despite having this fatigue. She enjoys hiking, gardening, and she's constantly volunteering at the senior center.
And so she is interested in therapy as long as she doesn't have to give up her activities and she definitely doesn't want therapy that's going to make her feel worse than she currently does. Imaging reveals the small-volume adenopathy above and below the diaphragm with the largest being about 4.2 cm, but her spleen's also enlarged at 17 cm and we pick up that there again is marrow uptake.
So she has an axillary node biopsy revealing low-grade follicular lymphoma. So in summary, this is an older patient. She has comorbid conditions. She's relapsing about 6 years out after single-agent rituximab. She is symptomatic from her lymphoma, but equally worried about how treatment might impact her quality of life.
How might you approach this case? So, Dr. Maddocks, we'll start with you. What are your thoughts about this case and what you might consider in terms of next steps?
Dr. Maddocks:
The good news for this patient is that she does have a lot of different options. But what I'm thinking about when I'm approaching this patient is her age and comorbidities, but also just her preference and how she wants to maintain quality of life. Things that I'm thinking about are her remission duration from the rituximab—she got a pretty prolonged time without any evidence of follicular lymphoma.
I'm thinking that possibly in consideration she wants low toxicity profile. She's responded well to antibody therapy before, had a good remission duration. I might just repeat single-agent antibody therapy for this lady. I think that that can be done in both terms of rituximab or you could consider obinutuzumab as well. We know that when you repeat single-agent antibody therapy, that responses do diminish and the PFS diminishes.
But I think with a 6-year timeframe, wanting quality of life preserved, that's probably what I'm going to think about. Now, she does have other options. You can add lenalidomide to this, you can add even more intensive therapy, but I think that she has a good chance of responding well to single-agent antibody therapy.
Dr. Nastoupil:
Dr. Casulo?
Dr. Casulo:
Yeah, I agree with Dr. Maddocks. I would probably select rituximab monotherapy again for this patient. The fact that she had 6 years of remission is really telling. It tells you that her biology is favorable. She had adequate disease control and let's say she gets another 4 or 3 years from a next rituximab monotherapy, we could even repeat it a third time. We may not get that much mileage out of it, but provided that she's not experiencing a lot of toxicity in terms of infections or things like that or hypogammaglobulinemia, I really like that approach for an older adult who really wants to focus on quality of life.
If she were maybe a little bit younger or if she were interested in something more intensive, we could consider adding the lenalidomide, like Dr. Maddocks suggested, depending on the tumor burden and how aggressive her presentation is, you might even think about chemotherapy for someone like that.
But in her particular case, given her presentation, I like the rituximab idea. We used to have tazemetostat for this situation, which would've been my go to for an older adult who just wants easy oral therapy, but that option's no longer available. So I think rituximab would be my choice.
Dr. Nastoupil:
And I'm glad you mentioned that because I was going to pick both of your brains about that. We had an agent that had a phenomenal safety profile but recently was removed from the market based off of challenges that were seen in the phase III study that combined it with lenalidomide and rituximab. And so how do we reconcile this is a patient that has had single-agent rituximab, is concerned about potential toxicity and maybe schedule of therapy that might take her away from her routine activities.
We did have these phase III studies with a triplet. Maybe this patient wouldn't have been eligible for either of those studies because she had a very good long remission following single-agent rituximab, but is the label going to restrict that use? And so how might you navigate this current treatment landscape knowing that there are some phase III studies that may be available to her that you might argue the efficacy looks really good. Now there's going to be a potential trade-off. So how do we consider those agents in this second line space? Kami, what are your thoughts?
Dr. Maddocks:
I think that there's a lot of excitement for some of the current agents in the earlier lines of therapy. If we look at the bispecific antibodies, if I was looking at this patient, I had her sitting in clinic, I would think about, "Hey, can we get you on a trial with mosunetuzumab if one existed in the second line?" Because I'm thinking maybe that'll give her a little more bang for her buck, but still a reasonable safety profile.
I would put a plug that there's an ongoing front-line trial looking at rituximab vs mosunetuzumab and that would be something I would consider even in front or second line for a patient if that were available. I do think it is a little bit challenging when we have these agents that we've seen like the R2 with epcoritamab, and you would love to use part of that regimen in this setting and that's a discussion I would have as well with a patient and think about looking for clinical trials.
Dr. Casulo:
I agree. I would also say that the treatment justifies the disease too. And for her, since it's like a relatively what sounds like a low tumor burden, possibly recurrence, it's unclear with the spleen size and her anemia, technically that counts as high tumor burden, but she was kind of walking that tightrope at the time of her first diagnosis anyway and she did really well with rituximab, which is an approach that's used in Northern Europe too.
So I would feel comfortable with that. I didn't suggest that epcoritamab/lenalidomide or tafasitamab/lenalidomide triplet in this case because of her desire that she's been very clear about to control her quality of life. I would be worried a little bit about this patient, given her age and comorbidities, would she be able to tolerate that toxicity? Would she even be able to finish the treatment, which is a year's worth of treatment at least? And so I think maybe just start with something a little gentler first and we can always use a bispecific in the third line if we need to.
Dr. Nastoupil:
And that raises another interesting aspect of how we approach follicular lymphoma because we do have different therapies available in different lines of treatment. And she was approached in frontline as maybe a patient that would've been eligible for the RESORT study. And I think, Kami, you highlighted this low tumor burden, a little borderline symptomatic. We're really trying to improve her symptoms. We achieved that with rituximab. She was observed. She potentially could be a candidate for retreatment at this stage and we know that that would be an effective strategy. And then when she relapses after that second round of rituximab that then opens the door to things like single-agent mosunetuzumab, for instance.
I think you both highlight really key aspects that yes, we have new options, but there might be patient specific characteristics or disease specific characteristics that inform whenever we're going to come in hard with three drugs vs a single-agent CD20 antibody.
Another question I want to pose to you, and Carla, you alluded to this. We still have all the options maybe that you might consider in frontline for someone who's a little bit more symptomatic. When would you consider to come in with chemoimmunotherapy after somebody may have had an immunotherapy option first line?
Dr. Casulo:
If she were to have had really bulky disease that needed rapid reduction in size, I probably would've considered chemotherapy for her. Probably not R-CHOP because if she ever transforms, it sounds like she's a relatively fit lady where you would want to give her the best treatment options possible if she were to transform later in life. I probably would use bendamustine-based treatment with the caveat that I would probably dose reduce in her given her renal injury and her age, not use obinutuzumab in this setting for her given that she's over the age of 70, we see more toxicity. So I have done that bendamustine and rituximab dose reduced for someone if they need rapid cytoreduction.
Dr. Nastoupil:
Well, perfect. Just to summarize your input on this case, follicular lymphoma is clearly a heterogeneous disease and there are several different management strategies given that these patients are probably going to see multiple courses of treatment over their lifetime that is likely going to extend decades. We're constantly balancing the safety and efficacy of a given regimen and engaging patients on what is important to them.
And so for patients like this with low-risk disease, she has several treatment options available to her and making sure that we mitigate the toxicity so that they can continue to achieve the goals that they're most interested in, I think is an important goal. And I appreciate that both of you landed on the fact that we could just re-expose her to single-agent CD20 antibody again and just see how she does.
And 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.
