Final results of a phase 2 trial confirmed a favorable risk-benefit profile of zanubrutinib plus obinutuzumab (ZO) in patients with relapsed or refractory follicular lymphoma (FL). Responses were durable, response rates increased over time, and safety was generally manageable, the researchers reported.
“While treatment advances have improved outcomes in FL, many patients experience multiple relapses with decreasing disease control intervals, highlighting the need for new therapies,” according to the authors, led by Marek Trneny of the Institute of Hematology Seràgnoli at the University of Bologna in Italy.
The ROSEWOOD study assessed obinutuzumab, a monoclonal antibody that binds to the CD20 protein on B cells and some cancer cells, helping the immune system destroy them. The study compared the combination of OZ and zanubrutinib, a next-generation Bruton tyrosine kinase inhibitor, with obinutuzumab monotherapy (O) in patients with relapsed or refractory FL who had received at least two prior lines of therapy.
Previous data from the study, at a median follow-up of 20.2 months, indicated significantly improved overall response rates with ZO vs O. The latest results are from a 34.6-month median follow-up.
The analysis included 214 patients with a median age of 64.0 years who had received treatment with ZO (n=143) or O (n=71). Most patients had high-risk features and had received a median of three prior lines of therapy.
The combination significantly improved overall response rate as compared with O alone (70.3% vs 44.4%), as well as complete response rate (42.1% with ZO vs 19.4% with O). These results were generally consistent among subgroups. Median duration of response was 32.9 months in the ZO arm compared with 14 months in the O arm. Median progression-free survival was 22.1 months in the ZO cohort compared with the 10.3 months in the O cohort. Notably, 36 patients (50%) in the O arm crossed over to receive ZO.
The most common treatment-emergent adverse events in the ZO arm were thrombocytopenia (21.7%), COVID-19 (20.3%), diarrhea (20.3%), and pneumonia (20.3%). The O group most commonly experienced pyrexia (19.7%), diarrhea (18.3%), nausea (16.9%), and neutropenia (16.9%). Adverse events led to treatment discontinuation in 21.7% of the ZO arm and 12.7% in the O arm. They led to death in 10.5% of the ZO arm and 9.9% in the O arm.
The authors noted that a phase 3 MAHOGANY study is currently comparing ZO with lenalidomide plus rituximab.
Reference
Zinzani PL, Mayer J, Flowers C, et al. Final analysis of the randomized phase 2 ROSEWOOD study of zanubrutinib + obinutuzumab vs obinutuzumab monotherapy in patients with relapsed/refractory follicular lymphoma. Abstract abs25-7171. Presented at: the 67th American Society of Hematology Annual Meeting and Exposition, Dec. 6-9, 2025, Orlando, FL.
