Risk of thrombosis and bleeding following CAR T-cell therapy: Insights from the Dutch "Follow that CAR!" registry.

Chimeric antigen receptor (CAR) T-cell therapy has significantly improved outcomes in patients with relapsed/refractory aggressive large B-cell lymphoma (R/R LBCL). Although thrombosis and bleeding complications have been increasingly reported, their clinical relevance and risk factors remain unclear, also due to heterogeneity between reporting studies. We investigated the incidence of thrombosis and bleeding in a more homogeneous real-world multicenter cohort by analyzing 250 adults with R/R LBCL who were included in the Dutch "Follow that CAR!" multicenter registry, and all received axicabtagene ciloleucel (axi-cel) CAR T-cell therapy. We assessed the impact of thrombosis and bleeding, incorporated as time-dependent covariates on overall survival and explored associations with cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), anticoagulant therapy, and laboratory parameters. One-year cumulative incidences of thrombosis and bleeding were 6.3% and 11.0%, respectively. Median time to thrombosis or bleeding was 28 days after infusion for both events. Bleeding was associated with poorer overall survival (hazard ratio [HR] 3.77, 95% CI 1.96-7.27). Patients with a CAR-HEMATOTOX score ≥2 before CAR T-cell therapy (HR 3.62, 95% CI 1.23-10.69), therapeutic anticoagulation at time of infusion (HR 3.74, 95% CI 1.33-10.49), or thrombocytopenia grade ≥3 (platelet count < 50 × 10