High-dose methotrexate, thiotepa, orelabrutinib combined with or without rituximab in primary or secondary central nervous system diffuse large B-cell lymphoma: a single-center retrospective analysis

Abstract

Purpose: Central nervous system lymphoma (CNSL) is an aggressive non-Hodgkin's lymphoma (NHL) confined to the central nervous system (CNS). Orelabrutinib is an oral second-generation Bruton tyrosine kinase (BTK) inhibitor and a novel therapeutic strategy for CNSL. The purpose of this study was to evaluate the effectiveness and safety of high-dose methotrexate (HD-MTX), thiotepa, and orelabrutinib combined with or without rituximab (MTO±R)regimen in the treatment of patients with CNSL. Methods: A total of 14 patients with CNS diffuse large B-cell lymphoma (DLBCL) were included in this retrospective study. All patients received the regimen MTO±R. Overall response rate (ORR), complete response rate(CR), partial response (PR), stable disease (SD), progressive disease (PD), progression-free survival (PFS), overall survival (OS), and the safety of MTO±R were assessed by the investigator. Results: Fourteen patients were evaluable for safety, and 13 patients were evaluable for efficacy. The overall CR rate was 69.2%, and the ORR was 92.3% for total patients. For PCNSL, the CR rate and ORR were 55.6% and 88.9%, respectively. For relapsed/refractory CNSL, the CR rate and ORR were 66.7% and 91.7%, respectively. The median follow-up time was 12.8 months. The median PFS was 11.3 months, and the median OS was not achieved. The 12-month PFS and OS rates were 60% and 70%, respectively. Adverse events occurred in 17 cycles, and Grade 3 AEs occurred in 5 patients (35.7%). Conclusion: MTO±R was an efficacious and well-tolerated regimen in patients with CNSL. A novel BTK inhibitor in combination with chemotherapy offers a new potential therapeutic strategy for patients with CNSL.