The Expanding Role of CAR T Cells in Lymphoma and Leukemia - Episode 3

R/R Large B-Cell Therapy in Managing Various Lymphomas

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Stephen J. Schuster, MD: Let’s talk about axicabtagene ciloleucel, or axi-cel. That was the first approved CAR [chimeric antigen receptor] T-cell therapy for lymphoma. About 4 to 6 months before that in pediatric ALL [acute lymphoblastic leukemia], there was approval of tisagenlecleucel. Technically, that smaller market was hit first by tisagenlecleucel. But in the big market, which is lymphoma, axi-cell [axicabtagene ciloleucel] was more common. We have mature data that Fred Locke published in Lancet Oncology last year.

Loretta J. Nastoupil, MD: One thing I’ll mention about this is that it’s a win for science, and it’s a win for clinical researchers, because I have patients beating on the door trying to get on these phase 1 studies, and it was something that was so novel, but it did reinvigorate our clinical research program. As you mentioned, some of the early publications were criticized based on the relatively short follow-up. The questions about whether this would be a durable treatment in a onetime therapy for patients with large-cell lymphoma. What we saw with Fred’s publication with longer follow-up, at the time he had about 27 months of median [MB1] follow-up. We didn’t see any new late-toxicity signals, which was incredibly important. The overall response rate, which was the best response rate, settled in at about 83%. And 58% of patients had achieved a complete response. ASH [American Society of Hematology Annual Meeting] this past year updated that with 3 years of median follow-up and shows that the overall survival had about 47% still alive at 3 years of follow-up. That starts to answer the question that yes, there is a subset of patients, approximately 40%, for whom we do think this is a definitive onetime therapy. The question remains, how can you improve outcomes for those 60% of patients where that’s not true?

Stephen J. Schuster, MD: I’ll tell you that 5 years ago, when we saw our large-cell lymphoma patients who were refractory to immunochemotherapy go into remission and not die within a year, that was very exciting. Now we’re talking about, “Wait, we didn’t cure them. What are we going to do now?” There was a time where we didn’t cure anyone. And you’re right. What’s impressive is, 40% of those patients, for 2 to 3 years are in remission. Most people, including the FDA, agree that 2 years is a pretty good benchmark. About 80% to 90% of relapses occur in large-cell lymphoma within the first 2 years anyway. These are good data. As Loretta said, 2 years is certainly a benchmark, in my opinion, for aggressive lymphomas. But Caron, would you feel as enthusiastic at 2 years for follicular lymphoma if you’re sitting on the FDA committee reviewing the new drug application?

Caron A. Jacobson, MD: I don’t think we can say anything about it being a definitive therapy for follicular lymphoma after 2 years. But if you think about the way it’s been tested in the third line and beyond, median [MB2] duration of responses to other available agents in that setting are under a year. If we continue to see more than half of patients maintain their response at 2 years, that’s a meaningful opportunity for patients with follicular lymphoma. I cannot say it’s definitive, though.

Stephen J. Schuster, MD: No, you are spot-on. It really depends on the patient population, right? As we were saying before this conference in our informal discussion, there are those who we know early on have a terrible prognosis, terrible meaning 50-50[MB3] chance of being dead at 2 years. That’s within the first 5 years, rather. You’ll know quickly. At the other end, for patients you’ve been following for 10 to 15 years, us old doctors, we know when they get to the end, what the survival is like when their remission duration becomes very short to the existing agents, under 12 months in most cases. That’s a group of bad actors. If you look at those patients, I would be impressed with 2 years in some of those. There are a group of patients with follicular lymphoma, despite the fact that it’s “indolent,” that I would be impressed with 2-year data. They’re the patients Caron described. There’s a subset of bad actors. It really depends on the eligibility criteria.

Transcript Edited for Clarity