Abstract Background: Central nervous system diffuse large B-cell lymphoma (CNS DLBCL) is a relatively rare extranodal non-Hodgkin lymphoma with high malignancy and poor prognosis. At present, the combined chemotherapy regimen based on high-dose methotrexate has been established as the first-line standard treatment regimen for CNS DLBCL. Studies have shown that most CNS DLBCLs are activated B-cell type diffuse large B-cell lymphomas (ABC-DLBCL), usually carrying mutations in MYD88 and CD79B. These molecular characteristics provide potential targets for targeted therapy. At present, a number of studies have shown that BTK inhibitors have significant anti-tumor activity in patients with ABC-DLBCL, especially those with both MYD88 and CD79B mutations. However, the efficacy and safety of the treatment regimen of zanubrutinib combined with rituximab and high-dose methotrexate in patients with CNS DLBCL need to be further verified through large-scale clinical trials. Objective: To investigate the efficacy and safety of zanubrutinib combined with rituximab and high-dose methotrexate regimen in the treatment of patients with CNS DLBCL. Methods: The clinical data of patients with CNS DLBCL who received zanubrutinib combined with R + HD-MTX treatment in the Affiliated Hospital of Southwest Medical University from November 2023 to July 2025 were analyzed. Results: A total of 7 patients were included, with a median age of 51 (38-67) years, including 2 males (28.6%) and 5 females (71.4%). There were 1 case (14.3%) of GCB subtype and 6 cases (85.7%) of non-GCB subtype. There was 1 patient (14.3%) with CD79B gene mutation, 3 patients (42.9%) with MYD88 gene mutation, and 1 patient (14.3%) with both CD79B and MYD88 gene mutations. Among them, 3 cases (42.9%) were primary central nervous system diffuse large B-cell lymphoma, and 4 cases (57.1%) were secondary central nervous system diffuse large B-cell lymphoma. One patient (14.3%) had received hematopoietic stem cell transplantation before, and the median number of treatment lines was 2. Efficacy was evaluated by PET/CT. All patients received zanubrutinib combined with rituximab and high-dose methotrexate regimen for at least 2 cycles, with a median of 4 cycles. The objective response rate (ORR) of the 7 patients was 100%, 6 patients (85.7%) achieved CR, and 1 patient (14.3%) achieved PR. Hematological adverse events (AEs) of grade ≥ 3 included neutropenia (57.1%) and thrombocytopenia (28.6%). Non-hematological AEs included pulmonary infection (42.9%), nausea (42.9%), diarrhea (14.3%), and liver and kidney function damage (42.9%). No atrial fibrillation or renal failure occurred in all patients. Conclusion: The zanubrutinib combined with R + HD-MTX regimen shows good efficacy and controllable safety in patients with CNS DLBCL, which may improve the prognosis of patients and is worthy of further research.
Hongyun Xing (Mon,) studied this question.