Single-Cell Analysis Reveals Ide-cel and Cilta-cel Characteristics That Influence Efficacy

Abstract

Chimeric antigen receptor T-cells targeting BCMA have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM) with two approved products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). To explore biological differences, we analyzed pre-infusion products (IP) and CAR-enriched peripheral blood mononuclear cells (PBMCs) at expansion using single-cell RNA sequencing (scRNAseq) from 52 samples. Post-quality control 247,500 cells (117,530 CD4, 80,939 CD8) were analyzed. We found that ide-cel IPs from durable responders (DR) had higher construct expression, enhanced NFKB signaling, and anti-apoptotic signatures, correlating with improved progression free survival. CAR + ide-cel PBMCs in DRs showed upregulated ribosomal genes and higher CD27, KLF2, TCF7 expression. Relative to ide-cel, cilta-cel CAR + cells showed higher expression of CD27, GZMK, TCF7, and a 4-fold increase in CAR expression. In addition, the TCR repertoire was less clonal and more diverse. This study elucidates the distinct characteristics of ide-cel and cilta-cel, offering insights into their differing clinical efficacy.