Background Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Approximately 30%-40% of patients experience relapse or become refractory after first-line treatment, with a poor prognosis. Traditional chemotherapy regimens have limited efficacy in these patients, and new treatment strategies are urgently needed. Zanubrutinib, a BTK inhibitor, can block B-cell receptor signaling by precisely inhibiting BTK, thereby suppressing tumor growth. In recent years, several clinical studies have suggested that zanubrutinib monotherapy or in combination with R-CHOP in the treatment of relapsed/refractory DLBCL (R/R DLBCL) can improve the objective response rate, prolong progression-free survival, and has manageable safety. These findings provide a new treatment option for patients with R/R DLBCL, but its long-term efficacy and optimal dosage regimen still need to be further verified through large-scale clinical trials.

Objective To investigate the efficacy and safety of zanubrutinib combined with chemotherapy in the treatment of patients with r/r DLBCL.

Methods The clinical data of 24 patients with r/r DLBCL who received zanubrutinib combined with chemotherapy in the Affiliated Hospital of Southwest Medical University from June 2023 to July 2025 were analyzed.

Results Among the patients included in this study, 16 cases (66.7%) had an IPI score of 3-5; 21 cases (87.5%) were in clinical stage Ⅲ-Ⅳ; and 6 cases (25%) were of the GCB subtype. The median age of the patients was 57 years; among them, 14 were female (58.3%) and 10 were male (41.7%). Two patients had received hematopoietic stem cell transplantation, 1 patient had received CAR-T therapy, and the median number of treatment lines for the patients was 2. In terms of treatment regimens, 2 patients were treated with zanubrutinib combined with R-CHOP (ZR-CHOP) regimen, 20 patients with zanubrutinib combined with R-GemOx (ZR-GemOx) regimen, 1 patient with zanubrutinib combined with Pola-R-GemOx (Pola-ZR-GemOx) regimen, and 1 patient with zanubrutinib combined with BR (Z-BR) regimen. All patients received at least 2 cycles of zanubrutinib combined with chemotherapy, with a median of 4 treatment cycles. Efficacy was evaluated by PET/CT, and the results showed that the overall objective response rate (ORR) was 75%, including a complete response (CR) rate of 33.3%, a partial response (PR) rate of 41.7%, and a progressive disease (PD) rate of 25%. Among them, the ORR of patients treated with the ZR-CHOP regimen was 100%, including a CR rate of 50% and a PR rate of 50%; the ORR of patients treated with the ZR-GemOx regimen was 75%, with a CR rate of 35%, a PR rate of 40%, and a PD rate of 25%; the PR rate of patients treated with the Pola-ZR-GemOx regimen was 100%; and the PD rate of patients treated with the Z-BR regimen was 100%. In terms of safety, grade ≥3 hematological adverse events (AEs) included: anemia (4.2%), neutropenia (58.3%), and thrombocytopenia (25%); major non-hematological adverse events included: pulmonary infection (45.8%), nausea (37.5%), diarrhea (16.7%), and neuritis (4.2%).

Conclusion The zanubrutinib combined with chemotherapy regimen shows good efficacy and controllable safety in the treatment of patients with r/r DLBCL, which may improve the prognosis of patients and is worthy of further research.

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2025
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