Tisa-Cel Yields Durable Responses in R/R Follicular Lymphoma

Derick Alison
Derick Alison
9 Min Read

Patients with relapsed/refractory follicular lymphoma experience durable responses when treated with tisagenlecleucel (tisa-cel, Kymriah) according to new 3-year data from the phase II ELARA study presented at the recent American Society of Hematology (ASH) annual meeting.

In this second of four exclusive episodes, MedPage Today brought together three expert leaders in the field, all from The Ohio State University Wexner Medical Center in Columbus — moderator Kami J. Maddocks, MD, is joined by Yazeed Y. Sawalha, MD, and David A. Bond, MDfor a virtual roundtable discussion on the encouraging follow-up data on the chimeric antigen receptor (CAR) T-cell therapy in this setting.

Following is a transcript of their remarks:

Maddocks: Let’s move on to our next abstract. So this abstract, “Clinical Outcomes of Patients with Relapse Refractory Follicular Lymphoma Treated with Tisa-Cel: Phase II ELARA 3-Year Follow-up.” So I think where there’s currently two chimeric antigen receptor T-cell products approved for relapsed/refractory follicular lymphoma, maybe you guys can comment on your experience with these and then this 3-year follow-up that was presented at ASH.

Bond: Yeah, I think with the emergence of the bispecifics, CAR-T maybe in some ways is a little bit overshadowed in follicular lymphoma, but I think it’s still an important option for treatment for our patients. And like you said, there’s two products that we have currently available for follicular lymphoma; and of those two, tisagenlecleucel — we see that that has a lower rate of CRS [cytokine release syndrome] and tends to just in general be more tolerable for patients that may have more comorbidities or be older. So it has been a drug that I’ve used in practice already for follicular lymphoma patients.

And so we got to see here updates from the ELARA study, which was the pivotal study that led to approval, and they had follow-up of over 3 years. I think the median follow-up was 37 months when it was presented. So you get a sense at least at that timeframe for how well the responses hold up. And I think what you see is that the responses do, at least for roughly half of patients, tend to seem to still be there at 3 years.

But beyond the 3 years, I think we’re all eager to see with more follow-up if you start to see more of a plateau. And I don’t think we can say that yet with just the 3-year median follow-up on this study. But you do see there were some patients up to 4 years that were still responding and in remission. So I think we’re excited to see further out there.

I think there was also interesting analysis just looking at the patients based on whether they had POD24 [progression of disease within 24 months], because we know those tend to be the patients that are more difficult to treat in practice. It did seem like at least numerically there was a shorter PFS [progression-free survival] for those patients, but still some of the patients that had POD24 still had a durable benefit. And there wasn’t a huge difference between the two groups of patients. I don’t think that that would necessarily lead you to not use this treatment for those high-risk patients; in some ways, [it] was reassuring that there’s efficacy at least for some people in that high-risk category.

Sawalha: Yeah, I agree. I think this was a very high risk patient population and median of four prior lines of treatment, high percentage of patients with POD24 and double refractory disease. But the outcomes were really remarkable. And again, with an additional year the CRs [complete responses] seemed to be durable. But I agree with you, David; I think especially in follicular lymphoma, we still have to wait longer until we maybe hopefully one day we’ll say we’re curing patients with follicular lymphoma with these treatments in the relapse setting.

Maddocks: Could either of you comment on the safety of this product?

Sawalha: Yeah, I think the safety data was very encouraging. So the risk of grade 3 or 4 CRS was only 1%, 50% overall had CRS, but mostly again these were grade 1 or 2 events. The risk of neurotoxicity was low also in this patient population. So overall I would say favorable risk. I would say one caveat a little bit is this is a younger patient population. So the median age is 57, there were patients up to the age of 73. So just one thing to keep in mind.

Bond: So not your typical, [not] necessarily the same patients that you’re seeing in clinic more often with follicular lymphoma, but also a more high-risk subset as well. And I think we have a lot of experience with tisagenlecleucel as a product that was approved early on for diffuse large B-cell lymphoma. And I think the safety that we see in follicular lymphoma seems to hold up with what we’ve seen with diffuse large B-cell where it tends to be a very tolerable CAR T product.

Maddocks: Okay, great. Any other thoughts on the current role of CAR in follicular lymphoma?

Sawalha: I think here in follicular lymphoma you can really make a very, very good case to try a bispecific anti before a CAR T-cell in the third line, I think it’s definitely a discussion with the patient, the pros and cons of each approach. I think the outcomes seem to be a little bit better with CAR T-cells, even though this is obviously cross-trial comparison. There’s a lot of limitations and caveats with that. But in an indolent disease, I think patients’ convenience [and] safety may be prioritized in this setting. And I think in that way a bispecific antibody might have an advantage.

Bond: Yeah, I agree. I think that some of the advantage to CAR T of it being a one-time treatment is attractive to patients, but some of the side effects that you see tend to be long lasting, including the cytopenias that can persist in some cases and in the B-cell aplasia and risk for infection. And that’s where I think getting longer follow-up with mosunetuzumab [Lunsumio] is interesting, but with that you still have an end to the time, although it’s a longer course of treatment. And I would say that comparing the two, you still have a more favorable side effect profile with mosunetuzumab compared with CAR T.

So I think in practice I have been prioritizing bispecifics, unless there’s a concern for transformed disease where we know that CAR T products are very efficacious with large B-cell lymphoma or a patient perhaps that’s progressed on prior bispecific antibody treatment.

Maddocks: I think sequencing these agents is like a whole other discussion.

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