Abstract
Relapsed or refractory central nervous system B-cell lymphoma (r/r CNS-BL), including primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL), remains a significant therapeutic challenge with limited treatment options and poor prognosis. This study investigated the combination of whole-brain radiotherapy (WBRT) and chimeric antigen receptor T-cell (CAR-T) therapy in 27 r/r CNS-BL patients. Peripheral blood mononuclear cells were collected before radiotherapy to prepare CAR-T cells. Patients then received whole-brain radiotherapy (WBRT), with or without local boost, followed by CAR-T cell infusion at least one week after radiotherapy completion. Post-CAR-T therapy, the optimal objective response rate (ORR) increased to 88.9%, and the optimal CR rate reached 85.2%. With a median follow-up of 12 months, the median progression-free survival (PFS) and overall survival (OS) were not reached (NR), and the 1-year estimated PFS and OS rate were 61.3% and 56.6%, respectively. Cytokine release syndrome (CRS) occurred in 48.1% of patients. Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 29.6% of patients, with only 3.7% on grade 4, all of whom recovered after treatment. This study demonstrates that the combination of WBRT and CAR-T therapy offers a promising therapeutic strategy for r/r CNS-BL patients, improving remission rates and providing a well-tolerated treatment option.