CAR T-Cell therapy for Myeloma: Where are we now and what is needed to move CAR T-cells forward to earlier lines of therapy? Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.

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Abstract

Since 2021, two B-Cell Maturation Antigen (BCMA) directed chimeric antigen receptor T-cell (CAR T-cell) therapies, Idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel), have been approved by the US FDA for relapsed or refractory multiple myeloma (RRMM) after four or more prior lines of therapy including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody. The two products have both shown unprecedented activity in RRMM, but relapses are still common, and access and safety of CAR T-cells in patients with rapidly progressing advanced disease is not ideal. Sequencing CAR T-cell therapy with other options, including the 2 recently approved BCMA directed T-cell engaging bispecific antibodies (TCE BsAbs) teclistamab and elranatamab, has become increasingly challenging due to data showing inferior outcomes from CAR T-cells after prior BCMA directed therapy. This has led to the consideration of using CAR T-cell therapy earlier in the course of disease for myeloma, when T-cells are potentially healthier and the myeloma is less aggressive. To address the question of earlier use of CAR T Cells, several trials are either ongoing or planned, and results have recently been reported for 2 randomized trials of CAR T-cells showing improved progression free survival compared to standard of care therapy in 2nd line (CARTITUDE-4) or 3rd line therapy (KarMMA-3). With the anticipation of the FDA possibly expanding approval of CAR T cells to earlier lines of myeloma therapy, the American Society for Transplantation and Cellular Therapy (ASTCT) convened a group of experts to provide a comprehensive review of the studies that led to approval of CAR T-cells in late line therapy of myeloma, discuss the recently reported and ongoing studies designed to move CAR T-cell therapy to earlier lines of therapy, and to share insights and considerations for sequencing therapy and optimization of patient selection for BCMA directed therapies in current practice.

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