Ciltacabtagene Autoleucel for the Treatment of Relapsed/Refractory Multiple Myeloma: Efficacy, Safety, and Place in Therapy.

Abstract

Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are two chimeric antigen receptor T cell (CAR T) therapies approved for use in patients with relapsed/refractory multiple myeloma (MM). Initially approved for late line MM (>4 prior lines), these were recently approved for use in MM with 1-2 prior lines of therapy in April 2024. As their use outside of the pivotal clinical trials continues to expand, it is important to critically evaluate the safety and efficacy of these therapies. Further, it is important to identify patients that would be most likely to benefit from the use of CAR T in earlier lines of therapy. Cilta-cel was initially studied in the phase-I LEGEND-2 study, followed by CARTITUDE-1 and CARTITUDE-4 trials, demonstrating remarkable efficacy. A recent large real-world study also demonstrated similar efficacy, in a mostly pivotal trial ineligible patient population. Based on these impressive results, cilta-cel is currently being studied in trials for newly diagnosed as well as smoldering multiple myeloma. Cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) are known toxicities of cilta-cel (and other CAR Ts), however movement and cognitive disorders (delayed neurotoxicity) and second primary malignancies are an evolving concern. In this article we discuss safety and efficacy data from existing cilta-cel studies. We propose that all patients with MM who have received ≥4 prior lines of therapy should be considered for CAR T. Earlier line use of CAR T should be restricted to patients with a high-risk disease phenotype (eg, functional high-risk disease). This disease phenotype has historically shown poor outcomes with standard triplet regimens and would be most likely to benefit from earlier use of CAR T: considering the availability of other safe and highly effective therapies, and potential high-risk toxicities of CAR T.