Late cytopenia after CD19 chimeric antigen receptor T cell in large B cell lymphoma: A Cell Therapy Consortium Analysis

Late cytopenia (beyond day+30 post-CAR T-cell) is a significant complication following CD19-directed chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). However, available data remain limited and heterogeneous. In this retrospective multicenter study, we evaluated the incidence, patterns, risk factors, and impact of late cytopenia in patients treated with CD19 CAR T-cells. A total of 444 patients with R/R LBCL at eight academic centers within the Cell Therapy Consortium between April 2016 and May 2023 were included. After excluding patients with events (relapse, new treatment, death) or lost to follow-up, grade ≥3 cytopenias were observed in 47%, 34%, 19%, 21%, and 11% of patients with available data at 1, 2, 3, 6, and 12 months post-infusion. Among 307 patients with complete hematologic data, neutropenia consistent with late immune effector cell-associated hematotoxicity was identified in 103 patients (33.6%) between days 30 and 100. Multivariable analysis identified a high CAR-HAEMATOTOX score (≥2) as a predictor of cytopenia at 3 months whereas receipt of bridging systemic chemotherapy and axicabtagene ciloleucel was associated with cytopenia at 6 months post-CAR T-cell. The presence of late cytopenia was associated with a higher 1-year non-relapse mortality (11% vs 4.4%, P=0.038), worse 2-year progression-free survival (38% vs 67%, P=0.035) and worse 2-year overall survival (60% vs 76%, P=0.016). In conclusion, late cytopenia is a common and clinically meaningful toxicity after CD19 CAR T-cell therapy. Recognition of risk factors and consistent monitoring are essential for optimizing post-CAR T-cell care and reducing treatment-related mortality.