Remission conversion drives outcomes after CAR T-cell therapy for multiple myeloma: a registry analysis from the DRST

ABSTRACT: Cellular therapies targeting B-cell maturation antigen have shown promise in controlled clinical trials, but their impact in broader, diverse patient populations remains underexplored. This study examines the real-world efficacy and safety in 343 triple-class-exposed patients with relapsed and refractory multiple myeloma who received idecabtagene vicleucel (ide-cel; n = 266) or ciltacabtagene autoleucel (cilta-cel; n = 77) after >3 previous lines of therapy in Germany. Cilta-cel, compared with ide-cel, demonstrated superior outcomes, achieving a higher overall response rate (94% vs 82%) and 10-month progression-free survival (PFS; 76% vs 47%). Cilta-cel also led to higher complete response (CR; 61% vs 39%) and improved response conversion, with more patients achieving CR after starting from less than CR before chimeric antigen receptor T-cell (CAR T) therapy. For those attaining CR after therapy, cilta-cel showed longer PFS, especially in patients who entered treatment with a partial response or worse. Cytokine release syndrome was observed in 85% of cilta-cel and 81% of ide-cel cases, predominantly low grade. Immune effector cell-associated neurotoxicity syndrome was more common with cilta-cel (25% vs 15%), although nonrelapse mortality at 10 months was comparable between therapies (7% vs 5%). Weighted multivariable analysis after propensity score matching confirmed a significant advantage in terms of PFS for cilta-cel, with a hazard ratio of 0.48. Overall, outcomes in our registry analysis were comparable with the pivotal trials that led to approval of the respective agents. Cilta-cel demonstrated a greater capacity for response conversion and durable remission. These findings underscore the need for individualized CAR T therapy selection to optimize patient outcomes.