BOVen (zanubrutinib BTK inhibitor + venetoclax BCL2 inhibitor + obinutuzumab anti-CD20) delivers 92% blood+marrow uMRD4 with ~80% 4-year PFS in frontline CLL

BOVen combines zanubrutinib (covalent BTK inhibitor), venetoclax (BCL2 inhibitor), and obinutuzumab (type II anti-CD20 mAb) as an MRD-driven, time-limited triplet in a multicentre, single-arm Phase 2 frontline CLL/SLL study (NCT03824483) with median follow-up 69 months and median treatment duration 10 cycles. The primary endpoint was met with 92% achieving uMRD4 (≤10^-4) in both blood and bone marrow (96% blood uMRD4); median MRD4-free survival was 34.1 months and 48-month PFS was 79.7% (95% CI 68.6-92.5)—in the ballpark of other fixed-duration venetoclax-based frontline regimens in fit patients (e.g., GAIA/CLL13 venetoclax–obinutuzumab 4-year PFS 81.8%; venetoclax–obinutuzumab–ibrutinib 85.5%), and numerically above the ~53% 6-year PFS reported with venetoclax–obinutuzumab in the older/comorbid CLL14 population. Grade 3–4 neutropenia was 25% and infections 9.6% (no grade 5), supporting the “shorter exposure” premise; an early MRD kinetic marker (ΔMRD400 at 4 months by immunosequencing) tracked with faster marrow uMRD4 (6 vs 12 months) and longer MRD4-free survival (50.5 vs 18.1 months) despite shorter treatment (8 vs 13 months), and the manuscript also describes zanubrutinib+venetoclax retreatment plus PK and T-cell profiling.