Impact of baseline severe cytopenia on post–BCMA CAR T-cell therapy outcomes in multiple myeloma: A propensity-matched multicenter study.

Abstract

e19527 Background: Severe cytopenias are common in relapsed/refractory multiple myeloma (MM) and may influence outcomes after B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy. However, comparative real-world data describing subsequent cytopenias and acute toxicities among patients with pre-index severe cytopenia remain limited. This study is one of the first real-world attempts to evaluate the association between baseline severe cytopenia and post–BCMA CAR-T cytopenia and toxicity outcomes in a propensity score–matched (PSM) MM cohort. Methods: We conducted a retrospective, propensity score–matched, multicenter cohort study using the US Collaborative Network (TriNetX). Adults with MM who received BCMA-directed CAR T-cell therapy (idecabtagene vicleucel or ciltacabtagene autoleucel) between January 1, 2021 and January 1, 2025 were included. Patients were stratified by presence versus absence of severe cytopenia within 3 months on or before MM diagnosis (Hb≤8 g/dL, absolute neutrophil count ≤0.50×10^3/µL, or platelets ≤50×10^3/µL). The index date was defined as first fulfillment of cohort eligibility. Outcomes were assessed beginning 30 days post-index without a prespecified end date. PSM (1:1, nearest neighbor) balanced prior transplant, chemotherapy exposure, and baseline laboratory parameters. Outcomes included post–CAR T cytopenias (individual and prolonged), hospitalization, and cytokine release syndrome, hemophagocytic lymphohistiocytosis, and immune effector cell–associated neurotoxicity syndrome. Risks were compared using measures of association, and time-to-event outcomes were analyzed using Kaplan-Meier methods with log-rank testing and hazard ratios with 95%CI. Results: After matching (n = 81 per cohort), mean age was 67.7±9.7 vs 66.8±8.8 years, with 60.5% vs 63.0% male patients. Median follow-up was 312 days (severe cytopenia) vs 191 days (no severe cytopenia). The severe cytopenia cohort had higher risk of anemia (29.6% vs 13.6%; RD 16.0%, p = 0.013) and prolonged cytopenia (40.7% vs 23.5%; RD 17.3%, p = 0.018). Time-to-event analyses showed increased hazard for anemia (HR 2.15, 95% CI 1.05–4.41; log-rank p = 0.032) and for prolonged cytopenia (HR 1.83, 95% CI 1.04–3.22; log-rank p = 0.032). Risks of neutropenia, thrombocytopenia, hospitalization, and CRS/HLH/ICANS were not significantly different (all RD p > 0.05; log-rank p > 0.15). Conclusions: In this propensity-matched real-world MM cohort receiving BCMA CAR-T, pre-index severe cytopenia was associated with higher subsequent rates and earlier onset of anemia and prolonged cytopenia beginning 30 days post-index, without a detectable increase in hospitalization or CRS/HLH/ICANS. These data support enhanced cytopenia monitoring and proactive supportive care strategies in patients presenting with severe cytopenia prior to CAR-T.