Efficacy and safety of orelabrutinib combined with rituximab and high dose methotrexate in primary or secondary central nervous system diffuse large B-cell lymphoma: a retrospective analysis.

Central nervous system lymphoma (CNSL) are mainly diffuse large B-cell lymphomas (DLBCLs). Orelabrutinib is a second-generation Bruton's tyrosine kinase (BTK) inhibitor and has shown single-agent activity in CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib combined with rituximab and high dose methotrexate (ORM) regimen in the treatment of patients with CNSL. We retrospectively analyzed data from CNSL patients treated with ORM regimen at Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University from April 2021 to October 2023. Patients receiving rituximab plus high-dose methotrexate (RM regimen) from June 2017 to January 2024 were identified as the control group. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A total of 32 patients were identified: 14 patients in the ORM group and 18 in the RM group. CR rates were 84.6% in the ORM group and 44.4% in the RM group (P = 0.032). Median PFS was 18.6 months in the RM group and 26.3 months in the ORM group (P = 0.133). Median OS was 34.1 months in the RM group and has not yet been reached in the ORM group (P = 0.041). Patients in the ORM group showed a higher 2-year OS rate than those in the RM group (82.1% vs. 57.5%). No grade 5 AE was reported in both groups. The incidence of grade 3-4 AE was comparable between the two treatment groups. ORM regimen was effective and well-tolerated in patients with CNSL. This combination therapy provides a new potential therapeutic strategy for patients with CNSL.