Efficacy and safety of bridging therapy prior to CAR T-cell therapy in relapsed or refractory multiple myeloma

Abstract

Disease burden at the time of BCMA-directed chimeric antigen receptor (CAR) T-cell infusion is a key determinant of outcome in relapsed or refractory multiple myeloma (RRMM). Bridging therapy is frequently administered between leukapheresis and infusion to prevent disease progression, yet its clinical impact remains unclear. We conducted a multicenter real-world cohort study of 399 patients with RRMM treated with BCMA-directed CAR T-cell therapy, including 348 (87%) who received bridging therapy. Bridging therapy recipients had more advanced and biologically adverse disease, including higher rates of high-risk cytogenetics and penta-class refractoriness. Bridging efficacy varied substantially by regimen (P<0.001). Bispecific T-cell engager-based bridging, particularly talquetamab, achieved the deepest responses and most effectively converted refractory disease prior to infusion, including in penta-refractory patients. Depth of response achieved after bridging was strongly associated with post-CAR T-cell progression-free survival, independent of baseline disease status. One-year progression-free survival ranged from 87% with talquetamab bridging to 52% with chemotherapy-based approaches. Bridging therapy did not impair subsequent CAR T-cell efficacy and was not associated with excess severe cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or nonrelapse mortality, although infection risk varied across regimens and was associated with pre-lymphodepletion immunoglobulin levels. In summary, these data demonstrate that bridging therapy is not a uniform intervention but a biologically and clinically consequential component of the CAR T-cell treatment pathway. Selection of highly active, immune-compatible bridging regimens can meaningfully improve pre-infusion disease control and post-infusion outcomes without compromising safety.