Outcomes of CD-19–directed CAR-T therapy in patients with primary and secondary central nervous system lymphoma: A multi-center observational study.

2038 Background: CD-19 directed chimeric antigen receptor T-Cell (CAR-T) therapies have been approved for the treatment of diffuse large B-Cell lymphoma; however, patients with primary central nervous system (CNS) lymphoma were excluded from pivotal registration trials. Although early-phase trials and meta-analysis suggest promising efficacy in CNS lymphoma, existing data remain limited by small sample sizes. We conducted a large, multicenter observational study evaluating outcomes of CD19-directed CAR-T therapy in patients with primary or secondary CNS lymphoma. Methods: This study utilized the TriNetX database, encompassing over 110 healthcare organizations, to evaluate outcomes of adults with a diagnosis of primary or secondary CNS lymphoma prior to receiving CAR T therapy between 2019 and 2025. Outcomes were assessed from the time of CAR-T infusion. The outcomes analyzed were 1-year overall survival, as well as development of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), treatment with tocilizumab, and risk of infection within 100 days post-CAR-T infusion. Kaplan-Meier estimated event rates were used to assess the primary outcomes. Results: We identified 155 patients with a diagnosis of primary or secondary lymphoma who received CD-19 directed CAR-T therapy. The median age at CAR-T infusion was 63 years. The cohort was predominately male (57%) and white (87%). A majority of the cohort, 80%, received Fludarabine/ Cyclophosphamide for lymphodepletion chemotherapy; 16% received Bendamustine. Most patients received axicabtagene ciloleucel (n=78), followed by lisocabtagene maraleucel (n=56), and tisagenlecleucel (n=21). The Kaplan–Meier estimated overall survival at one and three years was 63.9% and 46.9%, respectively. The estimated cumulative risk for CRS and ICANs post-CAR-T infusion was 58.7% and 26.5% respectively – 49.0% were treated with tocilizumab. The risk of infection by day 100 post-CAR-T infusion was 43.2%. Conclusions: CNS lymphomas have been associated with limited overall survival and represent an unmet need, necessitating the emergence of new therapeutic strategies. Our findings support the efficacy and safety of CAR-T in this population. To our knowledge, this is the largest single observational study of patients with CNS lymphoma treated with CAR-T. Outcome Time Point Rate (%)(n = 155) Overall Survival 1 years 63.9% 3 years 46.9% CRS 60 days 58.7% ICANS 60 days 26.5% Tocilizumab Use 60 days 49.0% Any Infection 100 days 43.2%