The Expanding Role of CAR T Cells in Lymphoma and Leukemia - Episode 5

Liso-cel Therapy in R/R Large B-Cell Lymphoma

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Stephen J. Schuster, MD: We’ve talked a lot about axi-cel (axicabtagene ciloleucel). Tisagenlecleucel is the 4-1BB-driven CAR (chimeric antigen receptor ) developed at Penn [University of Pennsylvania], and we’ve played a major role in its clinical development. We have data now that have been presented at 1 year, which was about one-third of patients who were responders [and] were still in remission at 1 year. I can tell you that that hasn’t changed at 2 years, although I’m not sure that that’s yet appeared in abstract form. But again, this is the same construct that was licensed from Penn to Novartis. We have follow-up in large-cell lymphoma now, median follow-up that’s 5 years. These responses are durable. At Penn, we received better than one-third. We were actually between 40% and 50% still in remission at 5 years, not because our vector was better at Penn, the one that was licensed to Novartis, or we made it better. It’s because in every single study, there [are] differences among patients, selections, and centers. There are so many variables that can influence the outcome, and I’m only comfortable saying it’s between 30% and 40% for any of these products in terms of durable remission. There are too many variables to sit down and compare studies side by side.

We have 2 available home runs. And we’re waiting for a third home run to come in later in this year. And that’s liso-cel, or lisocabtagene maraleucel. That is another 4-1BB-driven CAR developed by Juno and licensed to Celgene and now to BMS, [Bristol Myers Squibb], and they’re all one big happy family. Jeremy Abramson presented data at ASH [American Society of Hematology] last year, which I thought were pretty exciting, [first because of] the patient population. Every study is a little different. And just the way [it was] in follicular lymphoma, I’ll be impressed by 2 years if I know the patient characteristics; you really have to know the patient characteristics [when] comparing even large-cell studies. The data presented by Jeremy included some histologies [that] weren’t included in other aggressive lymphoma studies. For example, transformed marginal-zone lymphomas, you were allowed to have had CNS disease. That was not done for either of the other products. The data that were presented showed the CR [complete remission] rate was 40%, similar to what was shown with the other 4-1BB CAR. And one-third of those patients had ongoing CRs at 1 year. Looking like tisagenlecleucel, with a very low toxicity profile, which may be a historical artifact, because we’ve learned a lot about CRs and how to manage and prevent it. And earlier intervention leads to lower grades in the end. Not only are there patient selection characteristics, but we’re all victims of history, as well.

David Miklos, MD: We get different outcomes based on who the patients are that we put in, and, of course, if we do clinical trials that are very stringent, we get a more stringent outcome. If we do experiences, [such as] the real-world type of experiences where you can capture consecutive patients at large centers, then we get to have increased numbers and a little bit more variety. The retrospective analysis of those multivariates becomes very interesting.

Transcript Edited for Clarity