Ven-CLAG-M Nabs 65% CR in Adverse-Risk or Relapsed AML

Venetoclax, a BCL-2 inhibitor, was layered onto the intensive CLAG-M backbone (cladribine 5 mg/m² ×5 days, cytarabine 1.5 g/m² ×5, mitoxantrone 16/18 mg/m² ×3, plus G-CSF priming) in a first-in-human Phase 1 dose-escalation trial (NCT04797767). Twenty fit adults with newly diagnosed adverse-risk or relapsed/refractory AML/high-grade myeloid neoplasms received venetoclax 400 mg once-daily on days 1-14. Composite complete remission (CR + CRi) reached 65% with measurable-residual-disease negativity in many responders; 28-day mortality was 5%. Dose-limiting toxicities included grade 4 respiratory failure and sepsis, but the regimen’s early death rate mirrored historical CLAG-M (≈6-7%) while lifting CR from ~52-60% to 65%