P-011: Hematopoietic reconstitution and infections after anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma are associated with pre-CAR-T bridging therapies

Introduction: The time span from patient selection for CAR T-cells to actual infusion is challenging. Pre-apheresis and bridging therapies need to be carefully balanced between disease control, toxicities and effects on T cell fitness. The post-CAR-T phase is characterized by cytopenias and immune deficiency. Considering the diversity of therapeutic options in relapsed/refractory multiple myeloma (RRMM), we evaluated the effect of pre-CAR-T treatment regimens on reconstitution of bone marrow and immune function.

Methods: We performed a retrospective analysis of RRMM patients who received anti-BCMA CAR T-cells at our academic center. At data cutoff (May 22, 2023), 32 patients had undergone T cell apheresis and 29 patients had received idecabtagene vicleucel (ide-cel). We determined the last documented stable or progressive disease state leading to a systemic treatment prior to apheresis (‘pre-apheresis therapy’). ‘Bridging therapy’ was defined as any systemic treatment applied between apheresis and start of lymphodepletion. For analysis of the post-CAR-T phase, bridging therapies were divided into regimens with ≥ 2 (n=11), ≥ 1 (n=15), or no classical cytotoxic/chemotherapeutic (CTX) agents (n=10), with last cytotoxic drug administration ≤ 60 d before lymphodepletion and exclusion of patients with progressive disease and bone marrow infiltration > 5% (n=2) at time of reconstitution analysis. 14/32 patients had received cyclophosphamide, etoposide and dexamethasone (CED) as pre-apheresis therapy (n=4), bridging therapy (n=4) or both (n=6). Other bridging regimens with ≥ 2 CTX agents were CED-carfilzomib (n=1), BEAM (n=1) and pomalidomide-PACE (n=1).

Results: CAR T cell therapy with ide-cel resulted in an overall response rate (ORR; ≥ PR) of 72% (n=21), despite a high number of cases with R-ISS ≥ 2 (62%; n=18), high-risk cytogenetics (69%; n=20) and extramedullary disease (48%; n=14). With CED as pre-CAR-T treatment, 11/14 (79%) patients achieved at least stable disease. The ORR was 43% (n=6). Analysis of post-CAR-T hematopoietic reconstitution revealed a delayed recovery in patients after ≥ 2 CTX agents compared to all other bridging therapies. This included lower platelet counts at day 28 (p=0.025), day 35 (p=0.005), day 42 (p=0.009) and day 63 (p=0.015). Leukocyte counts were similarly different from day 28 onward, reaching statistical significance at day 35 (p=0.031), day 42 (p=0.030), day 63 (p=0.015) and day 90 (p=0.028). Two patients required stem cell support (both ≥ 2 CTX group). Infections between days 30 and 90 were more common among patients with ≥ 1 CTX bridging agent (18% vs. 67%; p=0.021).

Conclusions: The clinical efficacy achieved with ide-cel at our center was comparable with previously published data. CED is effective as pre-apheresis and bridging therapy for RRMM patients with high disease burden. However, CTX-intense regimens appear to be associated with an increased risk for prolonged cytopenias and infections after CAR T-cell therapy.