Efficacy and Safety of CAR T‐Cell Therapy for Primary and Secondary Central Nervous System Lymphoma: A Systematic Review and Meta‐Analysis

ABSTRACT Background Patients with relapsed or refractory primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) have limited treatment options and poor outcomes. CD19‐directed chimeric antigen receptor (CAR) T‐cell therapy has shown promising activity in this setting; however, the available evidence remains limited and heterogeneous. We performed a systematic review and meta‐analysis to evaluate its efficacy and safety. Methods A systematic search of PubMed, Google Scholar, Semantic Scholar, ClinicalTrials.gov and the Cochrane Library was conducted from inception to 31 August 2025. Twenty‐three prospective and retrospective studies involving 547 patients were included. Random‐effects meta‐analyses of proportions were performed to estimate pooled 12‐month overall survival (OS), 12‐month progression‐free survival (PFS), complete response (CR), cytokine release syndrome (CRS) and immune effector cell‐associated neurotoxicity syndrome (ICANS). Results The pooled 12‐month OS and PFS rates were 64.5% (95% CI, 49.0%–76.0%) and 51.0% (95% CI, 35.0%–68.0%), respectively. The pooled CR rate was 52% in PCNSL and 40% in SCNSL. CRS occurred in 76% of patients with PCNSL and 77% with SCNSL, while ICANS occurred in 50% and 46%, respectively. Most adverse events were manageable with standard supportive care. Conclusions CD19‐directed CAR T‐cell therapy is associated with encouraging survival and response outcomes and an acceptable safety profile in relapsed or refractory PCNSL and SCNSL. However, the available evidence is predominantly retrospective with clinical heterogeneity and relatively short follow‐up, underscoring the need for larger prospective studies with longer follow‐up. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.