Venetoclax plus azacitidine, low-dose cytarabine, aclarubicin, and G-CSF (VA-CAG regimen) for newly diagnosed young patients with acute myeloid leukemia: A prospective, multicenter, single-arm Phase II clinical trial.

We conducted a prospective, multicenter, Phase II study to evaluate the safety and efficacy of venetoclax/azacitidine/low-dose cytarabine/aclarubicin/granulocyte colony-stimulating factor (G-CSF) (VA-CAG) in young patients with newly diagnosed acute myeloid leukemia (ND-AML). The VA-CAG regimen included venetoclax (100 mg/day, Days 1-2; 200 mg, Day 3; 400 mg/day, Days 4-21), azacitidine (75 mg/m2, Days 1-7), cytarabine (10 mg/m2/12 h, Days 1-7), aclarubicin (12 mg/m2, Days 1, 3, 5, and 7), and G-CSF (5 μg/kg/day, Days 0-8). The primary endpoint was the complete remission (CR) rate after Cycle 1; the secondary endpoints included measurable residual disease (MRD)-negative remission rate, adverse events, and duration of remission (DOR). A total of 120 subjects were enrolled. The median age was 50 years (interquartile range, IQR, 36-57). The CR and composite complete response (CRc) rates were 91% (95% CI 86%-96%) and 95% (95% CI 91%-99%), respectively; 84% (95% CI 81%-88%) of the CRc patients achieved MRD-negative remission. Common Grade ≥4 adverse events included neutropenia (96%), thrombocytopenia (86%), febrile neutropenia (24%), pneumonia (4%), and sepsis (4%). The median times to recovery of absolute neutrophil count (ANC) ≥ 0.5 × 109/L and platelet count ≥ 20 × 109/L for responding patients were 14 days (IQR, 9-19) and 10 days (IQR, 4-16), and the 60-day mortality rate was 0%. With a median follow-up of 22.1 months (95% CI 20.4-23.7 months), 34 subjects subsequently received hematopoietic stem cell transplantation (HSCT). The median DOR values of all patients and the patients who did not receive HSCT were not reached. Hence, the VA-CAG regimen is a safe and effective first-line induction chemotherapy for ND-AML patients.