Immune correlates of anti-BCMA CAR-T products idecabtagene vicleucel and ciltacabtagene autoleucel in a real-world cohort of patients with multiple myeloma

Immune correlates of anti-BCMA CAR-T products idecabtagene vicleucel and ciltacabtagene autoleucel in a real-world cohort of patients with multiple myeloma

Abstract We performed the first in-depth, comparative and prospective biomonitoring of Multiple Myeloma (MM) patients (N = 39) receiving ciltacabtagene autoleucel (cilta-cel) or idecabtagene vicleucel (ide-cel) chimeric antigen receptor T cells (CAR T) in the real-world setting. In cilta-cel patient...

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Main Authors: Djordje Atanackovic, Tim Luetkens, Dina Schneider, Peirong Hu, Xu Wang, Amol C. Shetty, Luke Tallon, Imari Patel, Rohan Singh, Etse Gebru, Rediet Mulatu, Destiny Omili, Daniel Yamoah, Xiaoxuan Fan, Aerielle Matsangos, Patricia Lesho, Kenneth A. Dietze, Ariel A. Fromowitz, Kim G. Hankey, Saurabh Dahiya, Jean A. Yared, Nancy M. Hardy, Rima Koka, Michael E. Kallen, Ashraf Badros, Aaron P. Rapoport, Mehmet H. Kocoglu
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60980-2
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Summary:Abstract We performed the first in-depth, comparative and prospective biomonitoring of Multiple Myeloma (MM) patients (N = 39) receiving ciltacabtagene autoleucel (cilta-cel) or idecabtagene vicleucel (ide-cel) chimeric antigen receptor T cells (CAR T) in the real-world setting. In cilta-cel patients response rates were higher and atypical neurotoxicities/infections more frequent. Peak CAR T counts were significantly higher in cilta-cel patients, driven by CD4+ CAR expansion, correlating with clinical responses. Expansion of cilta-cel cells was associated with higher CAR and CD27 expression while, in contrast to ide-cel, there was no correlation between TIM3 expression and CAR T proliferation. Cilta-cel CAR T expansion was followed by a CAR-specific switch from proliferation-associated genes to genes/surface markers indicating effector/memory function. The longer persistence of cilta-cel CAR T was associated with increased IL-7R expression; in vitro data showed persistent antigen-independent activation and higher metabolic activity of cilta-cel vs. ide-cel CAR T. Among cilta-cel-treated patients experiencing atypical neurotoxicities, central nervous system (CNS)-infiltrating, effector-type CAR T presented a distinct inflammatory phenotypic/cytokine-expression profile. This in-depth biomonitoring report following real-world cilta-cel or ide-cel highlights intrinsic biological differences between BCMA-targeting CAR T products, potentially explaining differences in clinical activity and toxicity. Our findings may guide optimization of cellular immunotherapy strategies in MM.
ISSN:2041-1723

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