In a phase II trial (ROSEWOOD) reported in the Journal of Clinical Oncology, Zinzani et al found that the addition of zanubrutinib to obinutuzumab significantly improved objective response rate among patients with relapsed or refractory follicular lymphoma.

Study Details

In the open-label trial, 217 patients from sites in 17 countries who had received at least two lines of therapy (including an anti-CD20 antibody and an alkylating agent) were randomly assigned 2:1 between November 2017 and June 2021 to receive zanubrutinib plus obinutuzumab (n = 145) or obinutuzumab alone (n = 72). Zanubrutinib was given at 160 mg twice daily continuously in 28-day cycles until disease progression or unacceptable toxicity. Both groups received obinutuzumab at 1,000 mg on days 1, 8, and 15 of cycle 1, day 1 of cycles 2 to 6, and then every 8 weeks up to a total of 20 infusions (2-year maintenance). The primary endpoint was overall response rate on independent central review.

Outcomes

An objective response was observed in 118 of 143 evaluable patients (69%, 95% confidence interval [CI] = 61%–76%) in the combination group vs 34 of 71 evaluable patients (46%, 95% CI = 34%–58%) in the control group (P = .001); a complete response was observed in 39% vs 19% of patients (P = .004). The median duration of response was not reached (95% CI = 25.3 months to not estimable ) in the combination group vs 14.0 months (95% CI = 9.2–25.1 months) in the control group, with 69% vs 42% of responses ongoing at 18 months.

Median progression-free survival was 28.0 months (95% CI = 16.1 months to not estimable) in the combination group vs 10.4 months (95% CI = 6.5–13.8 months) in the control group (hazard ratio [HR] = 0.50, 95% CI = 0.33–0.75, P < .001). Median time to next treatment was not reached in the combination group vs 12.2 months in the control group (HR = 0.34, 95% CI = 0.22–0.52, P < .001).

Adverse Events

Grade ≥ 3 adverse events occurred in 63% of the combination group vs 48% of the control group; more common events in the combination group included thrombocytopenia (15% vs 7%), pneumonia (10% vs 4%), diarrhea (3% vs 1%), and dyspnea (2% vs 0%). In the combination group, atrial fibrillation occurred in 3% of patients and major hemorrhage, in 1%. Any-grade infection was reported in 55% vs 41% of patients. One treatment-related death was reported in the obinutuzumab group (from anaphylactic shock).

The investigators concluded: “The combination of [zanubrutinib and obinutuzumab] met its primary endpoint of a superior [overall response rate] versus [obinutuzumab] and demonstrated meaningful activity and a manageable safety profile in patients with [relapsed or refractory follicular lymphoma]. [Zanubrutinib and obinutuzumab] had a favorable benefit-risk profile compared with [obinutuzumab] and represents a potential combination therapy for patients with [relapsed or refractory follicular lymphoma].”

Pier Luigi Zinzani, MD, PhD, of the Seragnoli Institute of Hematology, University of Bologna, Italy, is the corresponding author of the Journal of Clinical Oncology article.

Disclosure: The study was supported by BeiGene. For full disclosures of the study authors, visit ascopubs.org.