Relapse patterns and clinical outcomes after BCMA-directed CAR-T therapy in multiple myeloma: a real-world single-center study

Abstract Background Despite deep remissions achieved with B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory multiple myeloma (MM), most patients eventually relapse. Although extramedullary disease (EMD) has been associated with poor prognosis after BCMA-directed CAR-T therapy, the clinical impact of distinct relapse patterns remains incompletely characterized, particularly in Asian populations. Methods This retrospective single-center study included 40 Chinese patients with MM who relapsed after BCMA-directed CAR-T therapy. Relapse patterns were classified as EMD, paramedullary disease (PMD), or biochemical-only. Post-relapse overall survival (OS), progression-free survival (PFS), and response to first-line salvage therapy were evaluated. Prognostic factors were analyzed using Cox regression. Results Median post-relapse OS was 20.0 months (95% CI, 15.7–not reached). Median post-relapse OS was 12.1 months (95% CI, 6.6–not reached) for EMD relapse, not reached (95% CI, 20.0–not reached) for PMD relapse, and 37.3 months (95% CI, 17.3–not reached) for biochemical-only relapse. In exploratory multivariable analysis, EMD relapse remained associated with inferior post-relapse OS (HR, 3.05; p = 0.019). The overall objective response rate (ORR) to first-line salvage therapy was 62.5%, with a median PFS of 6.2 months (95% CI, 4.7–15.4). Patients with EMD relapse had poorer salvage outcomes, with an ORR of 50.0% and a median PFS of 4.3 months (95% CI, 2.0–10.4). Conclusions In this real-world Chinese cohort, relapse patterns following BCMA-directed CAR-T therapy were associated with distinct post-relapse outcomes. EMD relapse was associated with inferior survival and poorer response to salvage therapy, highlighting the need for imaging surveillance in addition to laboratory monitoring during post-CAR-T follow-up.