ASH 2024 | Latest advances in the management of Richter’s transformation and future outlooks

Richter’s transformation is certainly exciting data that continues to evolve, but is still unfortunately lagging behind the massive advances that we’ve seen in the treatment of CLL/SLL itself. So, specifically as it pertains to bispecifics and cell therapies, CAR T cell therapies specifically, there is some encouraging data. This is already a viable option in that we have a label approval for epcoritamab and lisocabtagene maraleucel in the setting of large cell lymphoma transformed from a non-follicular indolent lymphoma. So that would include Richter’s transformation. Both are in the third-line setting. What’s problematic is what you see is using these later likely the deck is stacked further against you. Data to support this, so from a bi-specific perspective, we namely have the RT cohort from EPCOR-1 that Dr Kittai presented at EHA last summer. And so overall, I mean, if you look at the survival outcomes, median PFS are somewhat underwhelming. I think focusing rather in on the response rates and the duration of response, particularly in the patients who were able to have complete response and the patients who were treated earlier. So there was a subgroup of those patients who were treated in the first-line setting and I believe the complete response rate was 50 percent. So you’re going to hit some doubles or triples or home runs if you’re using this earlier perhaps or you have a better chance of it. If somebody’s kind of already been hit hard with multiple cytotoxics, you’re already working perhaps with some dysfunctional T cells in the setting of CLL and I think you may have the deck stacked a bit against you more. I think it’s encouraging that as well as data we’re seeing now at ASH, again updated this year I think with bispecifics with epcor and in the setting of CLL that you might be getting both components which is not something that you necessarily always got with some of the more kind of conventional you know large cell lymphoma regimen so if they have active CLL and usually it’s kind of nasty CLL that evolves into transforms into Richter’s these are therapies that can be treating kind of both components of the disease. From a CAR T perspective you know there’s, I guess, at each of the recent meetings starting last year, again, Dr Kittai had a large multicenter retrospective study of patients receiving various products, most of which was axicabtagene ciloleucel. There was then a CIBMTR analysis from Dr Winters at ASCO that was specifically liso-cel based on this approval, which actually looked better. I think those outcomes arguably looked even better than the TRANSCEND NHL data for non-Richter’s large cell. encouraging. And then at this ASH, the ERIC group is presenting again kind of a mix. I think maybe tisagenlecleucel is the most common product there. But either way, you’re seeing certainly there’s some patients that have a complete response and then they’re going to have a durable disease control. But unfortunately, I think there’s still quite a bit of room for improvement, either with CAR-T or with bispecifics, where the majority of patients, these treatments are still failing them. And so we need to continue to innovate to improve upon the efficacy of these encouraging and exciting options.

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