Late cytopenia after CD19 chimeric antigen receptor T-cell therapy in large B-cell lymphoma: a Cell Therapy Consortium analysis()

Late cytopenia (≥30 days after chimeric antigen receptor [CAR] T-cell therapy) is a significant complication after CD19-directed 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 treated at 8 academic centers within the Cell Therapy Consortium between April 2016 and May 2023 were included. After excluding patients with 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 after 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-HEMATOTOX score (≥2) as a predictor of cytopenia at 3 months, whereas receipt of bridging chemotherapy and axicabtagene ciloleucel was associated with cytopenia at 6 months after CAR T-cell therapy. The presence of late cytopenia was associated with a higher 1-year nonrelapse mortality (11% vs 4.4%; P = .038), worse 2-year progression-free survival (38% vs 67%; P = .035), and worse 2-year overall survival (60% vs 76%; P = .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 therapy care and reducing treatment-related mortality.