CAR-T cell therapy in the treatment of relapsed or refractory primary central nervous system lymphoma: recent advances and challenges.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive lymphoma that is isolated in the central nervous system (CNS) or vitreoretinal space. High-dose methotrexate (HD-MTX)-based immunochemotherapy is the frontline for its treatment, with a high early response rate. However, relapsed or refractory (R/R) patients present numerous difficulties and challenges in clinical treatment. Chimeric antigen receptor (CAR)-T cells offer a promising option for the treatment of hematologic malignancies, especially in the R/R B-cell lymphoma and multiple myeloma. Despite the exclusion of most PCNSL cases from pivotal CAR-T cell trials due to their specific tumor microenvironment (TME), available preclinical and clinical studies with small cohorts suggest an overall acceptable safety profile and remarkable anti-tumor effects. In this review, we will provide the development process of CAR-T cells and summarize the research progress, limitations, and future perspectives of CAR-T cell therapy in patients with R/R PCNSL.