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EBMT 2023 | Bringing CAR-T therapy in earlier lines of treatment in myeloma: KarMMa-3, CARTITUDE-4 & CARTITUDE-6

Mohamad Mohty, MD, PhD, Saint-Antoine Hospital, Paris, France, shares his enthusiasm for the advent of the two approved CAR-T therapies in multiple myeloma, ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), highlighting clinical trials evaluating these products in earlier lines of treatment (LOT). Prof. Mohty notably mentions the KarMMa-3 (NCT03651128) and CARTITUDE-4 (NCT04181827) studies evaluating ide-cel and cilta-cel respectively in earlier lines of relapse, and comments on the CARTITUDE-6 trial (NCT05257083) comparing autologous stem cell transplantation with cilta-cel following quadruplet induction therapy. This interview took place at the 49th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) held in Paris, France.

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Transcript (edited for clarity)

There is a lot of enthusiasm these days about the role of CAR T-cells in multiple myeloma. Definitely the two approved constructs named ide-cel and cilta-cel are excellent options for the relapsed/refractory patient with advanced stage multiple myeloma. Obviously now the question is how to bring these CAR T-cells earlier in the lines of therapy? Well, first issue is about bringing them into earlier lines of relapse and this is for instance, what we have seen in the KarMMa-3 trial that was presented during the presidential session at this EBMT 2023 annual meeting in Paris, where it was shown actually that the use of ide-cel in earlier relapse, is significantly better than the best available therapy...

There is a lot of enthusiasm these days about the role of CAR T-cells in multiple myeloma. Definitely the two approved constructs named ide-cel and cilta-cel are excellent options for the relapsed/refractory patient with advanced stage multiple myeloma. Obviously now the question is how to bring these CAR T-cells earlier in the lines of therapy? Well, first issue is about bringing them into earlier lines of relapse and this is for instance, what we have seen in the KarMMa-3 trial that was presented during the presidential session at this EBMT 2023 annual meeting in Paris, where it was shown actually that the use of ide-cel in earlier relapse, is significantly better than the best available therapy. This is really good news emphasizing the role and the potential benefit of introducing earlier CAR T-cells. Also, we are eagerly waiting for the results of the CARTITUDE-4 trial, which also investigated the use of cilta-cel in early relapse. We already know from a press release that the results are rather positive because the study met its primary end point, and this is again going in the same direction like the KarMMa-3 trial. Obviously, the next and probably more complicated step, is whether we’ll be able to bring these CAR T-cells into first line therapy and when we consider the first line therapy of young and fit multiple myeloma, we already know and until now, autologous stem cell transplantation is a standard of care. So, are we going to be able to replace auto-transplant and high dose melphalan with CAR T-cells? We need to have trials. Good news. The CARTITUDE-6 trial is already ongoing and it is exactly trying to answer this question. On one hand you have the standard of care arm, quadruplet induction, auto transplant, maintenance versus quadruplet induction, CAR T-cells and maintenance. Obviously, we still need another few years before we know these results. But definitely I think given the excellent safety profile but also the excellent efficacy of the CAR T-cell constructs we have today in hand, we are very eager to see these treatments going into earlier lines of therapy and time will tell.

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Disclosures

Gilead: Honoraria; GSK: Honoraria; Pfizer,: Honoraria; Adaptive Biotechnologies: Honoraria; Oncopeptides: Honoraria; Astellas: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Jazz Pharmaceuticals: Honoraria, Research Funding; Celgene: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.