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Immune correlates of anti-BCMA CAR-T products idecabtagene vicleucel and ciltacabtagene autoleucel in a real-world cohort of patients with multiple myeloma
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Immune correlates of anti-BCMA CAR-T products idecabtagene vicleucel and ciltacabtagene autoleucel in a real-world cohort of patients with multiple myeloma
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Immune correlates of anti-BCMA CAR-T products idecabtagene vicleucel and ciltacabtagene autoleucel in a real-world cohort of patients with multiple myeloma
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Journal Article
Immune correlates of anti-BCMA CAR-T products idecabtagene vicleucel and ciltacabtagene autoleucel in a real-world cohort of patients with multiple myeloma
2025
Overview
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.
Two BCMA-targeted CAR T products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have been approved for the treatment of multiple myeloma (MM). Here the authors report distinct expansion, phenotype, function, and toxicity of cilta-cel vs. ide-cel CAR T cells in a realworld cohort of patients with MM.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/1
/ 13/106
/ 13/21
/ 13/31
/ 13/51
/ 14/63
/ 38/91
/ 42/44
/ Aged
/ Antigens
/ B-Cell Maturation Antigen - immunology
/ Biological Products - therapeutic use
/ Blood
/ Female
/ Genes
/ Humanities and Social Sciences
/ Humans
/ Immunotherapy, Adoptive - adverse effects
/ Immunotherapy, Adoptive - methods
/ Male
/ Multiple Myeloma - immunology
/ Patients
/ Receptors, Chimeric Antigen - immunology
/ Science
/ Toxicity
