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

• This is the first nationwide registry study to validate clinical trial outcomes in RRMM, showing cilta-cel's superior compared to ide-cel

• Cilta-cel achieves better remission conversion than ide-cel, improving survival but linked to higher rates of severe side effects

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 (RRMM) who received idecabtagene vicleucel (ide-cel, n=266) or ciltacabtagene autoleucel (cilta-cel, n=77) after more than three prior lines of therapy in Germany. Cilta-cel as compared to 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 pre-CAR T. For those attaining CR post-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 non-relapse mortality at 10 months was comparable between therapies (7% vs. 5%). Weighted multivariable analysis after propensity score matching confirmed significant advantage in terms of PFS for cilta-cel, with a hazard ratio of 0.48. Overall, outcomes in our registry analysis were comparable to 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.