B-cell maturation antigen (BCMA) -targeting CAR T cells have revolutionized the treatment of relapsed/refractory multiple myeloma. In a comprehensive study involving 27 patients with RRMM treated with idecabtagene vicleucel (Ide-cel), researchers assessed the expansion capacity, persistence, and effects on bystander cells of CAR T cells. The findings indicate that in vivo expansion of CD8+ CAR T cells correlates with response, though persistence is not crucial for durable remission. Additionally, a higher fraction of CD8+ T cells at leukapheresis, combined with effective lymphodepletion, positively influences outcomes. Moreover, patients at risk for higher-grade cytokine release syndrome (CRS) can be identified before lymphodepletion, allowing for early intervention.

This extensive analysis contributes to a deeper understanding of BCMA-targeting CAR T cell dynamics, aiding in predicting individual patient responses and managing side effects. The study underscores the importance of initial CAR T cell expansion, predominantly driven by effector memory CD8+ CAR T cells, for treatment response and CRS occurrence. Responders and non-responders can be distinguished early by the cellular composition at leukapheresis, emphasizing the significance of disease burden control before CAR T cell therapy.

Reference: Fischer L, Grieb N, Born P, et al. Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma. Leukemia. 2024;38(2):372-382. doi: 10.1038/s41375-023-02129-y.