Venetoclax plus azacitidine vs. traditional chemotherapy in younger patients with Acute Myeloid Leukemia: A single-center real-world study

Abstract Objective: To compare the efficacy and safety of venetoclax plus azacitidine (V+A) versus traditional “3+7” chemotherapy as first-line treatment in patients <60 years with newly diagnosed acute myeloid leukemia (AML). Methods: This retrospective study enrolled 65 consecutive, newly diagnosed AML patients aged <60 years treated at our institution between January 1, 2019, and October 1, 2023. 30 patients received the “3+7” regimen (cytarabine + anthracycline), and 35 received V+A (venetoclax 400mg daily, days 1-28; azacitidine 75mg/m², days 1-7). Results: Baseline characteristics were balanced: median age 55 vs 56 years, male 47% vs 42%, high-risk cytogenetics 30.0% vs 22.9% in the traditional and V+A groups, respectively. Response: Complete remission (CR) rates after first induction were 70.0% (traditional) vs 74.3% (V+A). Composite complete remission (CRc, CR + CRi) rates were 73.3% vs 80.0%. Among CRc achievers, measurable residual disease (MRD) negativity rate was significantly higher with V+A (78.6% vs 36.4%, p<0.05). Subgroup Analysis (CRc rates): High-risk cytogenetics: 44.4% (traditional) vs 62.5% (V+A, p>0.05). IDH1/2 mutated: 50.0% vs 83.3% (p>0.05). FLT3 mutated: 77.8% vs 100.0% (p>0.05). NPM1 mutated: 81.8% vs 85.7% (p>0.05). TP53 mutated: 100.0% vs 50.0% (p>0.05; small subgroups). Survival: Median overall survival (mOS) was 24.8 months (95% CI: 13.2-36.4) for the traditional group and not reached (follow-up 3.9-37.0 months) for the V+A group. Safety: Grade ≥3 thrombocytopenia occurred in 93.3% (traditional) vs 68.6% (V+A, p<0.05), grade ≥3 anemia in 100% vs 62.9% (p<0.05), grade ≥3 neutropenia in 100.0%和83.3%（p>0.05. Grade ≥2 febrile neutropenia occurred in 60.0% vs 45.7%. Cardiac adverse events (e.g., heart failure, atrial fibrillation) were significantly more frequent in the traditional group (26.7% vs 5.7%, p<0.05). Conclusions: In this real-world cohort of younger, newly diagnosed AML patients, V+A demonstrated comparable CR/CRc rates to traditional “3+7” chemotherapy. However, V+A achieved significantly higher rates of MRD negativity and was associated with a more favorable safety profile, notably lower incidences of severe hematologic toxicities (anemia, thrombocytopenia) and cardiac events. V+A represents an effective and potentially less toxic alternative induction regimen for this population. Longer follow-up is needed to assess survival outcomes.