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

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 and Mehmet H. Kocoglu
Additional contact information
Djordje Atanackovic: University of Maryland Greenebaum Comprehensive Cancer Center
Tim Luetkens: University of Maryland Greenebaum Comprehensive Cancer Center
Dina Schneider: a Miltenyi Biotec Company
Peirong Hu: a Miltenyi Biotec Company
Xu Wang: a Miltenyi Biotec Company
Amol C. Shetty: University of Maryland Baltimore
Luke Tallon: University of Maryland Baltimore
Imari Patel: University of Maryland Greenebaum Comprehensive Cancer Center
Rohan Singh: University of Maryland Greenebaum Comprehensive Cancer Center
Etse Gebru: University of Maryland Greenebaum Comprehensive Cancer Center
Rediet Mulatu: University of Maryland Greenebaum Comprehensive Cancer Center
Destiny Omili: University of Maryland Greenebaum Comprehensive Cancer Center
Daniel Yamoah: University of Maryland Greenebaum Comprehensive Cancer Center
Xiaoxuan Fan: University of Maryland Greenebaum Comprehensive Cancer Center
Aerielle Matsangos: University of Maryland Greenebaum Comprehensive Cancer Center
Patricia Lesho: University of Maryland Greenebaum Comprehensive Cancer Center
Kenneth A. Dietze: University of Maryland
Ariel A. Fromowitz: University of Maryland Greenebaum Comprehensive Cancer Center
Kim G. Hankey: University of Maryland Greenebaum Comprehensive Cancer Center
Saurabh Dahiya: Stanford University
Jean A. Yared: University of Maryland Greenebaum Comprehensive Cancer Center
Nancy M. Hardy: University of Maryland Greenebaum Comprehensive Cancer Center
Rima Koka: University of Maryland School of Medicine
Michael E. Kallen: University of Maryland School of Medicine
Ashraf Badros: University of Maryland Greenebaum Comprehensive Cancer Center
Aaron P. Rapoport: University of Maryland Greenebaum Comprehensive Cancer Center
Mehmet H. Kocoglu: University of Maryland Greenebaum Comprehensive Cancer Center

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: 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.

Date: 2025
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60980-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60980-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60980-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().