Background
Phase II, randomized, open-label study. 217 patients with R/R FL (grade 1–3a) after ≥2 prior lines including anti-CD20. Zanubrutinib is a next-generation covalent BTK inhibitor with higher BTK occupancy and fewer off-target effects than ibrutinib. ROSEWOOD tested zanubrutinib + obinutuzumab versus obinutuzumab monotherapy in R/R FL.
Interventions and follow up
Arm A: Zanubrutinib 160mg PO BID + obinutuzumab 1000mg IV (days 1, 8, 15 cycle 1; day 1 cycles 2–6, then q2mo maintenance × 6 doses)
Arm B: Obinutuzumab 1000mg IV (same schedule) monotherapy
Primary endpoint: Overall response rate (independent review)
Median follow-up: 27.2 months
Arm B: Obinutuzumab 1000mg IV (same schedule) monotherapy
Primary endpoint: Overall response rate (independent review)
Median follow-up: 27.2 months
Results
ORR (primary): 69.0% vs 45.7%, P=.001
CR rate: 39.3% vs 19.3%
Median PFS: 28.0 vs 10.4 months, HR 0.50, 95% CI 0.33–0.75
24-month PFS rate: 49.5% vs 32.0%
CR rate: 39.3% vs 19.3%
Median PFS: 28.0 vs 10.4 months, HR 0.50, 95% CI 0.33–0.75
24-month PFS rate: 49.5% vs 32.0%
Adverse events
Hematologic (zanu+obin vs obin): Grade ≥3 AEs 50.4% vs 39.4%; grade ≥3 neutropenia 16.8% vs 19.3%.
Cardiac/bleeding/GI: Atrial fibrillation any grade 2.9% vs 0.9% (lower than ibrutinib); major bleeding 1.0% vs 0.9%; grade ≥3 diarrhea 1.0%.
Cardiac/bleeding/GI: Atrial fibrillation any grade 2.9% vs 0.9% (lower than ibrutinib); major bleeding 1.0% vs 0.9%; grade ≥3 diarrhea 1.0%.
Conclusions
Zanubrutinib + obinutuzumab significantly improved ORR (69% vs 46%) and PFS (HR 0.50) versus obinutuzumab alone in R/R FL, with a favorable safety profile including low atrial fibrillation rates, supporting FDA approval.
Key Limitations
Phase II randomized design — not a definitive phase III trial. Obinutuzumab monotherapy is not the standard comparator for R/R FL (R² or bendamustine-based regimens would be more relevant). The phase II sample size limits definitive efficacy conclusions. No comparison to bispecific antibodies (mosunetuzumab, epcoritamab) or CAR-T in this population. OS data immature.
Clinical Context
The FDA approved zanubrutinib + obinutuzumab (Brukinsa + Gazyva) for R/R FL after ≥2 prior lines in 2024. This adds another chemotherapy-free option alongside R², Pola-BR, and bispecifics. Zanubrutinib's improved BTK selectivity versus ibrutinib translates to lower rates of atrial fibrillation and major bleeding — relevant for the often-older FL population. ESMO recognizes BTK inhibitor-based combinations as an option in R/R FL.