Real-world effectiveness of zanubrutinib plus salvage chemotherapy in relapsed or refractory double-expressor DLBCL

To evaluate the efficacy and safety of the Bruton tyrosine kinase (BTK) inhibitor zanubrutinib in combination with salvage chemotherapy in patients with relapsed or refractory double-expressor diffuse large B-cell lymphoma (R/R DE-DLBCL). We performed a retrospective analysis of 35 patients with R/R DE-DLBCL treated at two hematology centers from June 2021 to June 2024. All patients received zanubrutinib combined with one of several salvage regimens, including zR-MINE, zR-DHAP, zR-GemOx, or zR2. Endpoints included objective response rate (ORR), complete response rate (CRR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). The median age was 60 years, and 91.4% of patients had the non-germinal center B-cell (non-GCB) subtype. At the end of therapy, the ORR and CRR were 45.7% (16/35) and 42.9% (15/35), respectively. After a median follow-up of 33.0 months, median PFS and OS were 8.0 and 12.0 months, respectively. Relapsed patients achieved a significantly higher CRR than refractory patients (56.5% vs. 16.7%, p = 0.034). On multivariate analysis, longer duration of response to prior therapy was an independent protective factor for OS (HR 0.88, 95% CI 0.77–0.99; p = 0.041). Grade 3–4 hematologic AEs were mainly neutropenia (42.8%) and thrombocytopenia (14.3%). Pulmonary infection was the most common non-hematologic AE (34.3%), and overall toxicity was manageable. Zanubrutinib combined with salvage chemotherapy demonstrates clinically meaningful activity with a manageable safety profile in patients with R/R DE-DLBCL and may represent a therapeutic option for this high-risk population. Sensitivity analysis confirmed the robustness of the observed survival benefit.