CAR-T Meeting 2022 | Advances in CAR-T therapy for R/R multiple myeloma: ide-cel & cilta-cel

It’s my pleasure to speak today about the novelties in the field of CAR-Ts for relapsed/refractory myeloma. I think over the last four or five years, we’ve seen lots of exciting data about the advent of immune therapy in the field of multiple myeloma. Whether this is about pharmacological agents: antibodies, antibody-drug conjugates, bispecific antibodies, T-cell engagers, or the classical monoclonal antibodies, like the anti-CD38 monoclonal antibodies, but also more recently the cellular immunotherapies, especially CAR-Ts. And we are very fortunate having now CAR-T constructs, namely ide-cel, which is now approved for relapse refractory multiple myeloma. And this approval was achieved thanks to a nice KarMMa study, which included 128 patients with highly advanced disease, a median of six lines of prior therapies, between 1 and 18. And the good news is that, despite being in a such heavily pretreated situation and highly advanced, these patients were able to achieve almost nine months of progression-free survival, but also up to 19 months of overall survival, highlighting the potency of CAR-Ts directed [inaudible] BCMA in this population.

However, I feel that this field will continue to progress and these results will continue to improve, especially with maybe other constructs. And we have now some strong data related to another CAR-T construct called cilta-cel. And this construct has a 4-1BB costimulatory domain but most importantly is that a BCMA catching domain targets two different epitopes simultaneously. And that may explain the results that could be achieved. For instance, in the CARTITUDE-1 trial, which is a phase Ib/II open-label multicenter study, it included 97 patients, median age 61 up to 78. So elderly age is not a contraindication. These patients received a median of six lines of prior therapies, between 3 and 18 lines. 24% had high-risk cytogenetics and 20% had plasmocytomas. The good news, the overall response rate is almost 98%. So clearly, a very high response rate. And the stringent CR rate is 82.5%. And when you look to the outcome data, progression-free survival or overall survival, actually, the two-year PFS is 71% in this cohort. And actually it is not reached yet in those patients who achieved a stringent CR. When it comes to safety, actually the results are very appealing because, in contrast to the story of CAR-Ts in lymphoma or acute lymphoblastic leukemia, the incidence of severe CRS or severe neurotoxicity is really very, very low.

So in summary, this highlights again that CAR-T approaches are highly attractive in relapsed/refractory multiple myeloma. I would personally consider the results are being impressive. Of course, the next step is to move these cells, these treatments into earlier lines of therapies and actually, there are now several ongoing studies. The KarMMa-3, the KarMMa-3, CARTITUDE-4, CARTITUDE-2, the [inaudible]. The PRIME study was another construct, the CRB-402, et cetera, et cetera. So a very exciting era in multiple myeloma, relying on the powers, the specificity, and the memory capacity of these cellular immune therapies.