To evaluate the efficacy, safety, and exploratory biomarker findings of zanubrutinib monotherapy in Chinese adults with CD79B-mutated relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Approach:
Design and participants: Open-label, single-arm, multicenter phase 2 trial; 65 patients enrolled from August 2021 through March 2025.
Treatment: Zanubrutinib 160 mg orally twice daily in continuous 28-day cycles until progression, unacceptable toxicity, or study discontinuation.
Outcomes: Primary endpoint was investigator-assessed overall response rate (ORR) using Lugano 2014 criteria. Secondary outcomes included complete response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
Key Findings:
After a median observation of 13.9 months, ORR was 46.2% (95% CI, 33.7–59.0), including a 29.2% complete response rate.
ORR exceeded the prespecified 30% historical control (one-sided P = 0.0044).
Among 30 responders, median time to response was 2.8 months and median DOR was 22.7 months (95% CI, 2.8–not estimable); 54.7% remained in response for at least 12 months.
Median PFS was 4.3 months (95% CI, 2.7–5.5), and median OS was 18.1 months (95% CI, 11.4–not estimable).
Activity was observed mainly in non-GCB DLBCL; the small GCB subgroup had no objective responses.
Any-grade treatment-emergent adverse events occurred in 90.8% of patients, and Grade 3 or higher events in 43.1%. The most frequent Grade 3 or higher events were pneumonia (9.2%), neutropenia (7.7%), and thrombocytopenia (6.2%).
Interpretation:
The authors report an ORR of 46.2% and a complete response rate of 29.2% with zanubrutinib monotherapy in this CD79B-mutated R/R DLBCL cohort. Any-grade treatment-emergent adverse events occurred in 90.8% of patients, and Grade 3 or higher events occurred in 43.1%.
Limitations:
The trial was open-label and single-arm, without a concurrent control group.
The study enrolled 65 patients, and the GCB subgroup was small.
Median observation was 13.9 months; the provided context does not report detailed exploratory biomarker results.
