Two successful phase 3 clinical trials of B cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells suggest that such agents could be used earlier in the treatment of patients with relapsed and/or refractory multiple myeloma, for which many effective treatments are available but no standard of care exists. Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) had previously shown efficacy in heavily pre-treated patients with relapsed or treatment-refractory multiple myeloma. The present studies demonstrate similar benefits for these CAR T cell therapies in patients who had received fewer pre-treatments.
In the CARTITUDE-4 study, cilta-cel conferred a reduced risk of disease progression or death versus physician’s choice of care (two regimens) in patients with lenalidomide-refractory disease who had received 1–3 previous therapies. Progression-free survival at 12 months was 75.9% (95% confidence interval (CI) 69.4–81.1%) in the cilta-cel group versus 48.6% (95% CI 41.5–55.3%) in the standard-care group. The rates of overall response (84.6% versus 67.3%), complete response (73.1% versus 21.8%) and absence of minimal residual disease (60.6% versus 15.6%) all favoured cilta-cel. Similarly, in the KarMMa-3 trial, ide-cel conferred a decreased risk of disease progression or death (hazard ratio 0.49, 95% CI 0.38–0.65, at a median 18.6 months of follow-up), as well as improved treatment response rates (71% versus 42%) and complete response rates (39% versus 5%) versus physician’s choice of care (five regimens) in patients who had received 2–4 previous therapies of ≥3 classes. No new safety concerns were raised: rates of cytokine release syndrome (CRS) were 88% (5% grade ≥3) with ide-cel and 76.1% (1.1% grade ≥3) with cilta-cel; neurotoxicity rates were 15% (3% grade ≥3) with ide-cel and 4.5% (none grade ≥3) with cilta-cel.
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