Immune effector cell associated hematotoxicity (ICAHT) with BCMA CAR T cell therapy in the earlier lines

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B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy is highly effective in relapsed/refractory multiple myeloma (MM), but adverse effects such as immune effector cell–associated hematotoxicity (ICAHT) remain a challenging early and long-term toxicity. Most reports on ICAHT originate from CAR T-cell therapies in late-stage MM, with limited data from earlier-line treatment. We conducted a multi-institutional retrospective study of 245 MM patients treated with BCMA CAR T, comparing ICAHT between early-line [early CAR T] (1–3 prior lines; n = 69) and late-line [late CAR T] (≥4 prior lines; n = 176) cohorts. Cytopenias (neutropenia ≤1000/µL, thrombocytopenia ≤50,000/µL, anemia ≤9 g/dL) were assessed at day 21 (D + 21), 3, and 6 months post-CAR T-cell infusion. At D + 21, ICAHT was less frequent with early CAR T versus late CAR T (39% vs 62%; p = 0.002), driven largely by lower thrombocytopenia (17% vs 39%; p = 0.001). At 3 months, ICAHT remained more common with late CAR T (30% vs 12%; p = 0.004), but by 6 months, rates converged (8.9% vs 18%; p = 0.126). Blood counts among patients with ICAHT at D + 21 often remained inferior at 3 and 6 months despite stem cell boosts. ICAHT at D + 21 independently predicted worse overall survival (HR 3.12; p = 0.022). Early-line CAR T-cell therapy was associated with superior 12-month PFS (87.8% vs 65.4%) and OS (96.2% vs 85.9%). These real-world data show that ICAHT occurs even with earlier-line BCMA CAR T-cell therapy, though less severe, and underscore the prognostic importance of early post-infusion cytopenias.

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