Impact of Intensive Cyclophosphamide-Containing Multi-Agent Bridging Therapy on Outcomes after Idecabtagene Vicleucel...

Bridging therapy (BT) is frequently required during manufacturing of B-cell maturation antigen-directed chimeric antigen receptor T-cell (CAR-T) therapy in relapsed/refractory multiple myeloma. In patients with aggressive disease, intensive cyclophosphamide-containing multi-agent chemotherapy may be selected; however, its post-CAR-T impact remains uncertain, partly due to potential confounding by indication. To evaluate the impact of intensive cyclophosphamide-containing multi-agent BT on clinical outcomes after idecabtagene vicleucel infusion in a real-world setting. We conducted a retrospective single-center cohort study of patients with relapsed or refractory multiple myeloma (RRMM) who received ide-cel between November 2022 and December 2025. Intensive BT was defined as VTD-PACE or DCEP (cyclophosphamide-containing multi-agent chemotherapy) and analyzed by the number of cycles (0/1/2). Progression-free survival (PFS) was estimated using Kaplan-Meier methods and compared with log-rank tests; multivariable Cox models were used to adjust for baseline disease aggressiveness. Hematologic recovery and grade ≥3 infections were evaluated using cumulative incidence methods with competing risks. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per the American Society for Transplantation and Cellular Therapy consensus grading. Among 94 patients (median follow-up, 12.5 mo by the reverse Kaplan-Meier methods), patients receiving intensive BT more frequently had aggressive disease at leukapheresis. The overall response rate (≥partial response) to BT was 75.5% and did not differ by cycle group (P = .32). Median PFS differed by cycle group in univariable analysis (P = .045), but intensive BT was not independently associated with inferior PFS after adjustment (hazard ratio [HR] 1.68, 95% confidence interval [CI] 0.45 to 6.24; P = .44). The second revision of International Staging System assessed at the time of leukapheresis remained independently associated with PFS (HR 2.30, 95% CI 1.06 to 4.98; P = .035). CRS occurred in 95.7% (grade ≥3, 2.1%) and ICANS in 5.3% (grade ≥3, 1.1%), with no difference by bridging intensity (P = .86 and P = .60, respectively). Intensive BT was associated with delayed platelet recovery >100 × 10⁹/L (P = .0096) and delayed neutrophil recovery >1.0 × 10⁹/L (P = .031). Grade ≥3 infections were similar across cycle groups (P = .29), including grade ≥3 viral infections (P = .12). Intensive cyclophosphamide-containing multi-agent BT (VTD-PACE/DCEP) was associated with delayed hematologic recovery but was not independently associated with inferior PFS after ide-cel when accounting for baseline disease aggressiveness. These findings suggest that intensive bridging may be considered for selected patients with aggressive RRMM requiring effective disease control prior to ide-cel infusion, with no statistically significant increase in CRS or ICANS.