Efficacy and safety of chimeric antigen receptor T-cell therapy in primary central nervous system lymphoma: a systematic review and meta-analysis

Abstract

Background Evidence for chimeric antigen receptor T-cell (CAR-T) therapy in primary central nervous system lymphoma (PCNSL) remains limited and heterogeneous, with prior syntheses often combining primary and secondary CNS lymphoma.Methods We systematically searched PubMed, Scopus, and Web of Science through February 2026. The protocol was not registered in PROSPERO. Twenty-three reports were included: 15 studies in the quantitative synthesis (194 patients) and 8 reports in the qualitative synthesis (9 patients).Results The pooled overall response rate was 68% (95% CI, 59–76; I2=17%), including a complete response rate of 57% (95% CI, 49–65; I2=4%) and a partial response rate of 16% (95% CI, 11–22; I2=0%). Pooled overall survival rates were 79% at 6 months and 60% at 12 months; progression-free survival rates were 52% and 42%, respectively. Safety outcomes showed pooled rates of 72% for any-grade cytokine release syndrome (CRS) and 12% for grade ≥3 CRS, while any-grade and grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 46% and 16%, respectively. Treatment-related mortality was 5% (95% CI, 2–15; I2= 0%). Sensitivity analyses yielded comparable results.Conclusions CAR-T therapy demonstrates promising efficacy with manageable toxicity in PCNSL. Although early disease control is encouraging, long-term durability remains limited.