Work

Impact of the kinetics of circulating anti‐BCMA CAR‐T cells and normal lymphocytes on the outcome of MM patients

Year: 2025

Type: article

Abstract: Chimeric antigen receptor (CAR)‐T‐cell therapy has improved response rates in relapsed/refractory multiple myeloma (RRMM), yet long‐term disease control remains limited, with only 20% of patients remaining progression‐free at 5 years. Therefore, identifying early predictors of treatment success is critical. Here, we used next‐generation flow cytometry to analyze T‐cell populations in blood at leukapheresis, before infusion, and post‐anti‐BCMA CAR‐T infusion, together with CAR‐T‐cell kinetics and phenotypes before, during, and after the expansion peak, in 53 RRMM patients. Anti‐BCMA CAR‐T cells peaked at Day +14 (72%), comprising >65 distinct populations, predominantly central memory (CM) T‐helper (Th) 1 and Th1/2 CAR‐TCD4 + and CM CAR‐TCD8 + cells. Multivariate analyses revealed that higher frequencies of TCD4 + naive and Th22 transitional memory (TM) cells at leukapheresis, together with circulating tumor plasma cells (CTPCs) before infusion, but none of the specific CAR‐T‐cell populations, were predictors of progression‐free survival (PFS). Based on these variables, we built a risk score that together with disease stage (International Staging System‐Revised [ISS‐R]) independently predicted, before CAR‐T‐cell infusion, which RRMM patients were most likely to benefit from anti‐BCMA CAR‐T therapy. These findings suggest that long‐term PFS is primarily influenced by the patient's immune landscape and the tumor burden rather than anti‐BCMA CAR‐T‐cell properties.

Source: HemaSphere

DOI: 10.1002/hem3.70277