Abstract
BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy is gradually reshaping the treatment paradigm for patients with central nervous system lymphoma (CNSL). However, the duration of remission (DOR) has remained the major challenge in existing studies. This study aimed to provide real-world long-term follow-up data on CAR-T therapy in CNSL patients and primarily investigate the impact of maintenance therapy on prolonging DOR. METHODS: This study evaluated the efficacy and safety of CAR-T therapy in 22 patients with CNSL, including 5 with primary CNSL and 17 with secondary CNSL (2025004, retrospectively registered). Maintenance therapy with programmed cell death protein-1 inhibitor (PD-1i) and Bruton's tyrosine kinase inhibitor (BTKi) was initiated in responding patients, while subgroup analysis comparing maintenance versus non-maintenance was restricted to those who achieved complete remission after CAR-T therapy. RESULTS: The best overall remission rate was 90.9%, with the best complete remission rate of 68.2%. With a median follow-up of 20.7 months (range, 3.1-88.9 months), the estimated 2-year progression-free survival and overall survival rates were 59.1% and 71.6%, respectively. No patient suffered severe immune effector cell-associated neurotoxicity syndrome, and only 3 patients experienced severe cytokine release syndrome. Patients who underwent PD-1i and BTKi maintenance achieved a 2-year DOR rate of 100%, which was significantly superior to those without maintenance therapy (Log-rank, P = 0.04). CONCLUSION: Our findings suggested the promising efficacy and manageable toxicities of CAR-T therapy in patients with CNSL. This study preliminarily proposed the concept that maintenance therapy may improve the DOR after CAR-T therapy.