Zanubrutinib, obinutuzumab, and venetoclax in CLL: long-term follow up, MRD kinetics, retreatment, T-cell profiling, and PKs.
Jacob D Soumerai, Meghan C Thompson, Ahmet Dogan et al.
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In 30 seconds
This phase 2 trial evaluated an MRD-guided course of zanubrutinib, obinutuzumab, and venetoclax (BOVen) in treatment-naïve chronic lymphocytic leukemia, including assessment of zanubrutinib–venetoclax retreatment and biomarker studies. After a median observation of 69 months and median treatment duration of 10 cycles, 92% achieved undetectable MRD at ≤10-4 in both blood and bone marrow. The 48-month progression-free survival was 79.7% (95% CI, 68.6-92.5). The regimen was reported as well tolerated, with durable remissions after relatively short treatment exposure.
Key findings
- Blood uMRD4 was achieved by 96% of participants, and blood and bone marrow uMRD4 by 92%.
- Median MRD4-free survival was 34.1 months (95% CI, 23.1-50.5); 48-month PFS was 79.7% (95% CI, 68.6-92.5).
- Grade 3-4 neutropenia occurred in 25% and infections in 9.6%; no grade 5 infections were reported.
- ΔMRD400 was associated with earlier bone marrow uMRD4 (6 vs 12 months, P< .001) and longer MRD4-free survival (50.5 vs 18.1 months, P< .001), despite shorter treatment.
Why it matters
The findings suggest that an MRD-guided triplet can produce frequent deep responses and sustained disease control in treatment-naïve CLL while limiting treatment duration. The association between early blood MRD reduction and subsequent outcomes may help inform efforts to individualize treatment duration, although the biomarker is still being evaluated prospectively.
What to keep in mind
This was a phase 2 trial; the abstract does not report a comparator arm. ΔMRD400 is undergoing evaluation and should not yet be treated as an established guide to treatment duration.