Treatment outcomes of zanubrutinib-based regimen in newly diagnosed patients with MYC/BCL2 double-expressor diffuse large B-cell lymphoma: a retrospective multicenter real-world study

Diffuse large B-cell lymphoma (DLBCL) patients with co-expression of MYC (≥ 40%) and BCL2 (≥ 50%), classified as double-expressor DLBCL (DE-DLBCL), consistently exhibit poor prognosis with traditional first-line therapies. In order to address the unmet therapeutic needs in this high-risk population, this real-world study retrospectively reviewd 46 newly diagnosed DE-DLBCL patients from two centers to evaluate the efficacy and safety of zanubrutinib-based regimens. Key outcomes included complete response rate (CRR), objective response rates (ORR), progression-free survival (PFS), overall survival (OS) and adverse events. Univariate analysis was conducted to evaluate the impact of various prognostic factors on complete response. The median age was 57.8 years (range:20-81), with 45.65% of patients over 60 years old and 17.39% over 75 years old. Advanced-stage (III/IV) disease was present in 60.87% of patients at diagnosis, 78.26% had a non-germinal center B-cell (non-GCB) subtype, and 41.3% exhibited an International Prognostic Index score ≥ 3. The best CRR was 73.90% (95% CI, 58.90%-85.70%), and the best ORR was 95.70% (95% CI, 85.20%-99.50%). At a median follow-up of 15.7 months, the 3-year PFS and OS was 86.27% (95% CI, 75.37%-98.75%) and 89.79% (95% CI, 78.40%-100%) respectively. Multivariate analysis revealed that zanubrutinib-based chemotherapy regimen significantly improved CRR. Significant differences in PFS were observed across age, bulky disease, IPI score, and extranodal involvement stratification. Adverse events were mainly hematologic toxicities and fatigue. These findings suggest that zanubrutinib may serve as an effective component of first-line therapy for this population, with favorable tolerability.