The efficacy and safety of venetoclax and azacitidine combined with granulocyte-colony stimulating factor in the treatment of Acute Myeloid Leukemia

Abstract Objective This study was designed to evaluate the efficacy and safety of the azacitidine-venetoclax-G-CSF (VAG) combination regimen compared with a control regimen of idarubicin-cytarabine in newly diagnosed patients with acute myeloid leukemia (AML). Methods This is a retrospective study of VAG Regimen in newly diagnosed AML (ND-AML) patients. 40 ND-AML patients were treated at the Second People's Hospital of Huai'an and Siyang County Traditional Chinese Medicine Hospital, China, from January 2022 to September 2023. 24 patients received the VAG regimen, which consists of: Azacitidine subcutaneously at 75 mg/m2 on days 1-7, Venetoclax started at 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-28, G-CSF administered intravenously starting on day 1 when the peripheral blood white blood cell count was less than 4 × 10⁹/L, with the goal of maintaining the white blood cell count below 25 × 10⁹/L. For comparison, 16 ND-AML patients treated with the standard IA induction regimen at the same institution between October 2019 and April 2023 were included. The IA regimen consisted of: Idarubicin 10 mg/m2/day on days 1-3, Cytarabine 100 mg/m2/day on days 1-7. The primary end points were overall response rate (ORR) and complete response (CR) and CR with incomplete recovery (CRi). Results 1. Patient Characteristics and Response Rates A total of 40 ND-AML patients were enrolled in this study. 24 patients were treated with the VAG regimen, with a median age of 63 years (range: 18–83), 16 patients received the IA chemotherapy regimen, with a median age of 48 years (range: 19–64). Comparative efficacy analysis between the VAG and IA groups revealed the following: ORR: 100% (24/24) in the VAG group vs. 93. 7% (15/16) in the IA group. CR/CRi rate: 88% (21/24) in the VAG group vs. 62. 5% (10/16) in the IA group. MRD Negativity in CR/CRi Patients: 95. 2% (20/21) in the VAG group vs. 50% (5/10) in the IA group. 2. Subgroup analysis by age demonstrated: Elderly Patients (≥60 years): CR/CRi rate of 85. 7% (12/14) in the VAG group vs. 75% (3/4) in the IA group. Younger Patients (18–60 years): CR/CRi rate of 90. 0% (9/10) in the VAG group vs. 58. 3% (7/12) in the IA group. ELN Risk Stratification and Subtype Analysis VAG Group: Low-risk: CR/CRi rate of 100% (5/5). Intermediate-risk: CR/CRi rate of 88. 9% (8/9). High-risk: CR/CRi rate of 80. 0% (8/10). M5 Subtype: CR/CRi rate of 75% (3/4), compared to 90. 0% (18/20) for other subtypes. IA Group: Low-risk: CR/CRi rate of 62. 5% (5/8). Intermediate-risk: CR/CRi rate of 75% (3/4). High-risk: CR/CRi rate of 50% (2/4). M5 Subtype: CR/CRi rate of 33. 3% (2/6), compared to 80% (8/10) for other subtypes. Genetic Subgroup Analysis VAG Cohort: DNMT3A, STAG2, and NPM1 mutations: Achieved a 100% CR/CRi rate (6/6, 4/4, and 4/4). FLT3-ITD mutation: CR/CRi rate of 100% (2/2). CEBPA and TET2 mutations: CR/CRi rate of 75% (3/4 each). SRSF2 mutation: CR/CRi rate of 60% (5/7). ASXL1, BCOR, and RUNX1 mutations: CR/CRi rate of 50% (2/4, 1/2, and 1/2). NRAS mutation: CR/CRi rate of 40% (2/5). IA Cohort: CEBPA and KRAS mutations: CR/CRi rate of 100% (4/4 and 2/2). FLT3-ITD mutation: CR/CRi rate of 83. 3% (5/6). ASXL1, KIT, TET2, and DNMT3A mutations: CR/CRi rate of 50% (1/2 each). NRAS mutation: CR/CRi rate of 33. 3% (1/3). 5. Treatment-Related Adverse Events and Supportive Care VAG vs. IA Group: Median duration of neutropenia: 7. 83 days vs. 16. 88 days. Median duration of thrombocytopenia (20 × 10⁹/L): 4. 54 days vs. 15. 06 days. Mean red blood cell transfusions: 6. 68 units vs. 12. 72 units. Mean platelet transfusions: 3. 92 units vs. 6. 41 units. The most common grade 3 or higher adverse events in the VAG group included neutropenia (38%), febrile neutropenia (23%), thrombocytopenia (38%), and anemia (38%). Gastrointestinal symptoms were reported as the primary non-hematologic adverse events, all of which were manageable and classified as grade 1-2. No treatment-related deaths were reported in either group. Conclusions In ND-AML patients, no matter whether they were elder or younger patients, the VAG regimen demonstrated a higher response rate compared to the IA regimen. This suggests that the VAG regimen offers a promising treatment option for both young and elderly patients with ND-AML. Key words Acute myeloid leukemia; Venetoclax; Azacitidine；Granulocyte-Colony Stimulating Factor；