Published on January 27, 2026
A Longitudinal Single-cell Atlas to Predict Outcome and Toxicity After BCMA-directed CAR T Cell Therapy in Multiple Myeloma
by Alex Khadhim
Researchers at University Hospital of Leipzig and Memorial Sloan Kettering Cancer Center have demonstrated that the BCMA CAR T product ciltacabtagene autoleucel appears to deliver deeper and longer remissions than idecabtagene vicleucel in relapsed or refractory multiple myeloma, which track with specific CAR T cell states in patients. In a longitudinal single cell multi-omics study published in Cancer Cell, the group links ciltacabtagene responses to expansion of cytotoxic CD4 CAR T cells that support tumor clearance but also align with clinically important immune toxicities, and they identify plasmacytoid dendritic cells as a non-B lineage compartment with notable BCMA biology that may matter for both efficacy and off-tumor effects.
BCMA CAR T therapies can induce deep remissions, but outcomes remain heterogeneous and severe toxicities still occur, so there is a major need for biomarkers that go beyond baseline clinical risk. The investigators analyzed 61 consecutive patients (median age 64 years; median 7 prior lines of therapy) treated with ide-cel (n=34) or cilta-cel (n=27). They performed longitudinal single-cell profiling with paired antigen-receptor sequencing and flow-based CAR tracking across leukapheresis and multiple post-infusion time points, then integrated these data with tumor burden markers such as soluble BCMA and inflammatory readouts such as CRP to connect immune dynamics with progression-free survival and CRS biology.
Clinically, cilta-cel produced higher complete response rates than ide-cel (78% vs 38%), with higher MRD negativity (33% vs 3%, p=0.03), higher conversion to CR after initial response (52% vs 38%, p=0.04), and longer progression-free survival (median not reached vs 11 months, p=0.02). Baseline extramedullary disease was associated with inferior PFS (p=0.0068), and high baseline soluble BCMA (>49.6 ng/mL) was linked to shorter PFS (p=0.017). For toxicity, 67% developed grade I to II CRS, and 37% of CRS cases required tocilizumab (no CRS n=20; CRS without tocilizumab n=26; CRS with tocilizumab n=15); CRS incidence differed by product (79% ide-cel vs 52% cilta-cel, p=0.03). Early expansion tracked inflammation, with CAR-positive cell proportions at day 7 correlating with maximum CRP (p=0.011) and increasing with CRS grade (p=0.002), and grade I to II CRS showing higher peak CRP (p=0.002). Overall, these findings support immune-state, timepoint-specific monitoring to forecast who is likely to sustain remission versus develop inflammatory complications, which could guide earlier interventions and more personalized CAR T management.
Reference:
Rade M, Fandrei D, Kreuz M, et al. A longitudinal single-cell atlas to predict outcome and toxicity after BCMA-directed CAR T cell therapy in multiple myeloma. Cancer Cell. Published online December 4, 2025. doi:10.1016/j.ccell.2025.10.014
http://doi.org/10.1016/j.ccell.2025.10.014
![]()