Adding Zanubrutinib to Obinutuzumab Improves PFS in Relapsed/Refractory FL

Adding zanubrutinib to obinutuzumab appears to improve both response rate and progression-free survival (PFS) among patients with relapsed or refractory follicular lymphoma (FL), according to research published in the Journal of Clinical Oncology.

Obinutuzumab, an anti-CD20 monoclonal antibody, has previously demonstrated efficacy in this patient population, with past clinical trials suggesting an overall response rate (ORR) of 45% regardless of whether a patient was refractory to rituximab.

Zanubrutinib is a Bruton tyrosine kinase inhibitor that has shown promise in B cell malignancies, including relapsed or refractory FL. For the randomized phase 2 ROSEWOOD study (ClinicalTrials.gov Identifier: NCT03332017), researchers compared the safety and efficacy of combination zanubrutinib plus obinutuzumab vs that of obinutuzumab alone among patients with relapsed or refractory FL.

Overall, of the 217 patients enrolled and randomly assigned to therapy per ROSEWOOD criteria, 143 were treated in the combination arm and 71 in the monotherapy arm. In the overall cohort, the median age was 64 years, the median number of prior therapy lines was 3, and 82% of patients had Ann Arbor stage III or IV disease.

The median follow-up was 20.2 months. Analysis showed that ORR, per independent central review, was 69% in the zanubrutinib group vs 46% in the obinutuzumab monotherapy group (P =.001); the complete response rates were 39% vs 19%, respectively, and the 18-month duration of response rates 69% vs 42%.

Furthermore, in addition to the ORR benefits, median PFS was 28 months in the combination therapy group vs 10.4 months in the monotherapy group (hazard ratio, 0.5; P <.001).

Commonly observed adverse events with zanubrutinib were thrombocytopenia, neutropenia, diarrhea, and fatigue. Atrial fibrillation and major hemorrhage were, respectively, noted in 3% and 1% of patients in this group.

“In the context of the limited availability of effective low-toxicity therapeutic options for [relapsed/refractory] FL, a phase III study of [zanubrutinib plus obinutuzumab] versus lenalidomide plus rituximab in this setting is now underway (MAHOGANY; ClinicalTrials.gov Identifier: NCT05100862),” the authors wrote in their report.

Disclosures: This research was supported by BeiGene. Please see the original reference for a full list of disclosures.

Reference
Zinzani PL, Mayer J, Flowers CR, et al. ROSEWOOD: A phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma. J Clin Oncol. Published online July 28, 2023. doi:10.1200/JCO.23.00775

This article originally appeared on Hematology Advisor