Zanubrutinib Plus Obinutuzumab vs Obinutuzumab Monotherapy for Patients With R/R Follicular Lymphoma

Phase 2 Results from the ROSEWOOD Trial

Second-generation BTK inhibitor zanubrutinib combined with anti-CD20 monoclonal antibody obinutuzumab demonstrated meaningful activity, manageable safety, and a favorable risk/benefit profile compared with obinutuzumab alone for the treatment of patients with relapsed/refractory (R/R) follicular lymphoma (FL), according to results from the phase 2 ROSEWOOD trial.

A total of 217 patients with R/R follicular lymphoma who had previously received 2  or more lines of therapy, including an anti-CD20 antibody and an alkylating agent, were randomized on a 2-to-1 basis to receive zanubrutinib plus obinutuzumab or obinutuzumab monotherapy. 

The primary end point of this trial was overall response rate (ORR), which was evaluated by independent central review. Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival, and safety. The trial met its primary endpoint, with ORR by independent central review measuring at 69% from zanubrutinib plus obinutuzumab versus 46% from obinutuzumab monotherapy (P = .001). 

Complete response rate was 39% for the combination therapy versus 19% for the monotherapy. The 18-month duration of response rate was 69% for zanubrutinib plus obinutuzumab versus obinutuzumab, at 42%. The median progression-free survival was 28 months with zanubrutinib plus obinutuzumab versus 10.4 months with obinutuzumab (hazard ratio, [HR] 0.50 [95% confidence interval [CI], 0.33 to 0.75], P < .001).

The most common adverse events noted with zanubrutinib plus obinutuzumab were thrombocytopenia, neutropenia, diarrhea, and fatigue. Occurrences of atrial fibrillation and major hemorrhage were 3% and 1%, respectively.

Study investigators concluded, “in a population of patients with R/R FL previously treated with at least 2 lines of therapy, the combination of zanubrutinib and obinutuzumab demonstrated a favorable risk/benefit profile and may represent a novel treatment option.” 

“In the context of the limited availability of effective low-toxicity therapeutic options for R/R FL, a phase [3] study [MAHOGANY] of zanubrutinib and obinutuzumab versus lenalidomide plus rituximab in this setting is now underway,” they added. 

“Contrary to previous single-arm studies, this randomized phase [2] trial demonstrates efficacy of BTK inhibition combined with anti-CD20 therapy in FL. Ongoing phase [3] studies will better define the optimal place for this regimen over the disease course,” explained Journal of Clinical Oncology editor-in-chief, Jonathan W Friedberg, MD.

Source:

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