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Relapsed/Refractory Follicular Lymphoma Treatment Armamentarium
Author(s):
Switching focus back to relapsed/refractory follicular lymphoma, Sameh Gaballa, MD, and Matthew Lunning, DO, FACP, consider the list of available treatment options in this setting.
Transcript:
Sameh R. Gaballa, MD: Let’s now review the options available for patients with relapsed/refractory disease. Over the last 2 or 3 years, we’ve really had a lot of changes. In terms of the options available, as we discussed previously, you could rechallenge again with single-agent rituximab, obinutuzumab. There is chemoimmunotherapy. So a patient, for example, who’s had R-bendamustine could get R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone] again. But again, my personal approach for these patients is [to] typically reserve the R-CHOP for patients where I’m suspecting disease transformation. For patients with relapsed/refractory disease, the most common regimen that currently I use is R2 [lenalidomide and rituximab] in the second line, and that’s based on the AUGMENT [trial; NCT01938001] data. The results have been updated at the last ASH [American Society of Hematology] meeting, and there’s now an overall survival advantage. Not all patients are going to be good candidates for R2. Patients with renal impairment, for example, or some patients who are elderly or infirm. For those patients, I may recommend something like [tazemetostat] in the second line just because of its superior safety profile. In the third line and beyond, we’ve now had mosunetuzumab, just approved in December in the US. It was previously approved and available in in Europe. CAR [chimeric antigen receptor] T-cell therapy is also available for these patients. We have axi-cel [axicabtagene ciloleucel] and we have tisa-cel [tisagenlecleucel], but that patient profile typically is patients who [maybe have] more high-risk disease, younger patients [who are] expected to have a long survival, and you might want to proceed with a therapy that provides you the longest remission duration. Bispecifics are interesting because we’ve all seen the data where with mosunetuzumab, we need longer follow-up.
There is data for [INAUDIBLE] as well combining it with lenalidomide, and the results look very interesting. As a matter of fact, they look very close to what we’re seeing with CAR T, but the problem is the follow-up duration is still short. It was just updated at the annual ASCO [American Society of Clinical Oncology] meeting, but we need longer follow-up to really try to tease out where will this treatment really fits. I see in the not-so-distant future where bispecifics, either alone or combination with other agents, would be used in earlier lines in follicular lymphoma, even before CAR T. That’s very different than diffuse large B-cell lymphoma, because in diffuse large B-cell lymphoma, we’re trying to cure their disease. Right now, the most data that we have is really with CAR T. But as we get longer follow-up for patients on bispecifics, I think that will help clarify that question. What has been your approach for these patients with relapsed or refractory follicular lymphoma?
Matthew A. Lunning, DO, FACP: I think that I have tried to be a steward of the POD24 [progression of disease within 2 years] concept, but truly the POD24 [patients who] are progressing within 24 months of the start of their therapy. I’m not classically scanning them. It’s the person at a year after therapy, so at about 18 months, and they’re coming in and their disease is coming back, that in my mind is a real POD24, and I’ve tried to put them on the SWOG trial or have the discussion about the SWOG trial. Let’s say they got BR [bendamustine plus rituximab] first. That’s a randomized trial now with obinutuzumab, lenalidomide versus chemo, and we still have this discussion, right or wrong, about [autologous] transplant consolidation. The sweet spot is in their second line, where we, at least historically, at our own institution has have seen plateaus on that curve. Obviously, it’s a different era now with many more therapies than that. I think that if you’re going to have that discussion, it should be done in the second-line setting, from a clinical trial. I think R2 is the backbone for me, either off a clinical trial, because the data has shown that POD24 really hasn’t mattered necessarily in that setting to the opportunities for long-term disease benefit. But if they’re not on a clinical trial, which is R2 plus something, whether it’s tazemetostat or epcoritamab, as you alluded to from the Merryman abstract from just this year at ASCO, which looked very impressive.
Where are we going? There’s also the discussion about CAR T-cell and where is that going to fit into the equation? I 100-percent agree with you. I think [epcoritamab or epcoritamab-mosunetuzumab]; those trials are going to jump ahead of CAR T-cell in follicular lymphoma, whether or not it’s single agent or if it’s in combination. CAR T-cell [therapy is] going to be reserved for that patient who still has follicular lymphoma on a biopsy but is behaving like a large-cell lymphoma, or, very rarely, probably less than 5% of follicular lymphomas are double refractory, right? You got their BR [bendamustine plus rituximab] and they still had progressive disease, and then they got R2 and they didn’t respond. In my mind, that’s a CAR T-cell patient, especially after I biopsied them probably both times, and it’s still follicular lymphoma. So I know the real-world data is out there from Caron Jacobson and colleagues showing that we can get people the CAR T-cell [therapy] in the real world. In the real world is completely different than the clinical trial world in lymphoma, just in general about how you get people to CAR T-cell [therapy]. But also I think it’s going to be a challenge. ZUMA-22 is coming up, it’s a [phase 3] planned trial [NCT05371093] looking at axi-cel versus standard care and relapse/refractory follicular lymphoma. That’s going to be a trial that’s probably going to take years to read out, right? Because it’s a clinical trial population, and it’s probably going to be the population that can wait to get on a clinical trial. So I think there are a lot of moving pieces on the chess board right now in follicular lymphoma, and I don’t think we know when to move the rook and when to move the bishop, but it’s a fun situation to be in where we have a lot of therapies to offer our patients when they are in need of therapy.
Transcript edited for clarity.
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