Efficacy and hematopoietic recovery of high-dose melphalan with stem cell rescue as bridging to CAR-T compared with non-intensive bridging in relapsed/refractory multiple myeloma.

7544 Background: Bridging therapy is required for disease control in relapsed/refractory multiple myeloma (RRMM) patients awaiting CAR-T. Recent data suggest intensive cytotoxic bridging impairs post-CAR-T hematopoietic recovery. We compared melphalan-based therapy with stem cell rescue (MBT) versus talquetamab (T), a GPRC5D-directed bispecific antibody. Methods: We performed a retrospective single-center study of RRMM patients bridged with MBT or T prior to CAR-T (June 2021–December 2024) post apheresis. Cytopenias were graded per CTCAE v5.0 during early (within 30 days of CAR-T) and late (beyond 30 days of CAR-T) periods. Kaplan Meier analysis was performed to evaluate survival outcomes. Results: Of 242 CAR-T recipients, 34 received bridging either with T (n = 21, 62%) or MBT (n = 13, 38%). MBT patients were younger (61.9 vs 67.2 years; P = 0.08); high-risk cytogenetics by FISH were similar (92% vs 85%; P = 0.58). Bridging response rates were comparable (92% vs 82%; P = 0.36).At 20 months, 64% MBT and 58.7% T patients remained progression-free. Early grade 3–4 neutropenia for MBT vs T: 92% vs 95% (P = 0.37); late: 46% vs 33% (P = 0.84). Early grade 3–4 thrombocytopenia MBT vs T: 31% vs 24% (P = 0.28); late: 15% vs 14% (P = 0.40). Early grade 3 anemia MBT vs T: 69% vs 38% (P = 0.18); late grade 3–4: 17% vs 10% (P = 0.35). Median recovery times (MBT vs T): ANC 10 vs 5 days early (P = 0.28), 19 vs 17 days late (P = 0.11); platelets 7 vs 7.5 days early (P = 0.30), 12 vs 49 days late (P = 0.20); hemoglobin 13.5 vs 9 days early (P = 0.49), 35 vs 93 days late (P = 0.65). CRS rates were comparable: 53.8% vs 63.6% (P = 0.57). ICANS occurred only in the T cohort (13.6%) (p = 0.08). Conclusions: MBT yielded hematopoietic recovery, toxicity, and outcomes comparable to bispecific antibody bridging. These findings contrast with prior studies showing impaired recovery after intensive cytotoxic bridging, likely because stem cell rescue improves hematopoietic reserve. Prospective studies are warranted.