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/m 2 , Days 1–7), cytarabine (10 mg/m 2 /12 h, Days 1–7), aclarubicin (12 mg/m 2 , 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 × 10 9 /L and platelet count ≥ 20 × 10 9 /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.