BCMA-directed CAR-T cell therapy in relapsed/refractory multiple myeloma: efficacy, safety, survival, and future...

Multiple myeloma is an incurable hematologic malignancy, although therapeutic advances have improved survival. BCMA-directed CAR-T cell therapy has shown high response rates in relapsed or refractory multiple myeloma (RRMM), but efficacy and toxicity vary across trials. A rigorous synthesis of current evidence is needed to better define these outcomes.

We performed a systematic review and meta-analysis of prospective interventional trials published from inception to January 2026 evaluating BCMA-targeted CAR-T therapies in adults with RRMM. Trials reporting efficacy or safety outcomes were included. Pooled estimates with 95% confidence intervals (CI) were calculated in R. Heterogeneity was assessed using the I² statistic, publication bias with Egger's regression, and stability with leave-one-out sensitivity analysis.

Fourteen clinical trials including 1,278 patients with RRMM and a median of 3 to 8 prior lines of therapy were included^1-4. The pooled overall response rate (ORR) was 86% (95% CI: 80-90%; I² = 75.9%). Grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3% of patients (95% CI: 2-4%; I² = 0%). Discontinuation due to toxicity occurred in 4% (95% CI: 1-9%; I² = 68.2%), and treatment-related mortality in 5% (95% CI: 3-9%; I² = 64%). Additional efficacy and safety outcomes, including disease control rate and grade ≥ 3 hematologic toxicities, were also assessed.

BCMA-directed CAR-T cell therapy demonstrates high efficacy in RRMM with a low incidence of severe neurotoxicity. However, severe hematologic toxicities are frequent and treatment-related mortality remains clinically relevant, highlighting the need for optimized patient selection and toxicity mitigation.