Venetoclax (BCL-2 inhibitor) + azacitidine: 28-day induction trends to higher CR vs 14-day in OPTI-AML ND-AML

Venetoclax (Ven; oral BCL-2 inhibitor) plus azacitidine (Aza; hypomethylating agent) was tested in OPTI-AML (NCT03013998), a prospective randomized Phase 2 trial in genomically agnostic newly diagnosed AML patients ≥60 years, comparing 28 days of Ven (AV28; n=83) vs 14 days (AV14; n=86) during cycles 1–2 with Aza 75mg/m² ×7 days. CR within 2 cycles was 49.4% (AV28) vs 43.0% (AV14), a 6.4% difference (90%CI −6.1% to 19.0%) that failed non-inferiority; CRc was 80.7% vs 68.6% with similar MRD negativity (77.6% vs 76.5%). Despite more treatment interruptions with AV28, count recovery after cycle 2, grade ≥3 AEs, and early mortality were similar; compared with VIALE-A’s Ven+Aza benchmark (CR/CRi ≈66% and median OS 14.7 months), both arms here land within the expected response band for Ven+Aza doublet therapy in older/unfit ND-AML.