This study used multidimensional and computational flow cytometry to characterize endogenous and CAR-T cell phenotypes in 258 bone marrow aspirates from 107 relapsed/refractory multiple myeloma (RRMM) patients treated with idecabtagene vicleucel (ide-cel) in the KarMMa Phase 2 trial, examining associations with progression-free survival (PFS) at screening and at Months 1, 3, 6, and 12 post-infusion.
At screening, higher percentages of PD1+ cytotoxic T cells and ICOS−TIGIT+ Tregs associated with longer PFS (HR ≥5.0 for low vs. high). At Month 1 post-infusion, >1% bone marrow CAR-T cells, CD4:CD8 CAR-T ratio >0.09, and greater non-activated CD4+ CAR-T cells predicted longer PFS; higher ICOS+TIGIT− Tregs at the latest post-infusion timepoint strongly predicted shorter PFS (median 2.4 months vs. not reached; HR 5.25, 95% CI 1.60–17.28; p=0.006).
- Small subgroup sizes in some analyses due to the maxstat cutoff methodology limit reliability of specific thresholds. - Effects of lymphodepletion versus CAR-T infusion on endogenous T-cell phenotype changes cannot be separated. - Findings are from a single-arm Phase 2 trial without external validation cohort; the study requires replication in independent datasets.
Bone marrow CAR-T cell quantification and CD4:CD8 ratio at Month 1, and endogenous Treg phenotyping at later timepoints, may help identify ide-cel patients at high risk of early progression—pending external validation, these markers could guide closer monitoring or earlier salvage strategies.
