CAR-T cell therapy for relapsed or refractory multiple myeloma in 2024—clinically available treatment options in Austria

Chimeric antigen receptor (CAR)-T cell therapy has become an established approach in the treatment of relapsed or refractory multiple myeloma (RRMM). Currently, two BCMA-targeted CAR-T cell constructs are approved for use in RRMM: idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel). The two pivotal studies, KarMMa (Ide-cel) and CARTITUDE‑1 (Cilta-cel), enrolled patients after at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and a CD38 antibody. The median progression-free survival (PFS) in the KarMMa study was 8.8 months and 20.2 months for patients who achieved a complete remission. CARTITUDE‑1 showed unprecedented results with a median PFS of 34.9 months in this difficult-to-treat patient population. These pivotal studies were followed by two randomized phase 3 trials, both of which demonstrated a significant improvement in PFS in patients treated with one of the two CAR‑T constructs compared to standard therapy. Side effects of CAR-T cell therapy are dominated by cytokine release syndrome and hematologic toxicity in the majority of patients and neurotoxicity of variable severity. A number of factors have to be taken into account in the selection of patients and the choice of the CAR‑T construct, such as comorbidities and disease risk profile. In the coming years, CAR-T cells will undoubtedly move into early lines of therapy and the repertoire will be expanded with additional CAR‑T constructs.