Efficacy and safety of azacitidine, venetoclax combined with gha priming regimen in the treatment of adult refractory and relapsed acute myeloid leukemia: A prospective single-arm multicenter study

Abstract Objective: To investigate the efficacy and safety of azacitidine, venetoclax combined with GHA priming regimen in the treatment of adult refractory/relapsed acute myeloid leukemia. Methods: A total of 28 patients with refractory/relapsed acute myeloid leukemia (AML, excluding acute promyelocytic leukemia M3) admitted between December 26, 2024, and May 31, 2025, were included. All patients met the definition of refractory/relapsed acute myeloid leukemia as specified in NCCN Guidelines version 1.2024 for AML. These patients were treated with the combination regimen of azacitidine (75 mg/m², days 1-7) + venetoclax (400 mg, days 1-10 or days 1-14) combined with the GHA priming regimen (homoharringtonine 1 mg, days 1-7; low-dose cytarabine 10 mg/m², every 12 hours, days 1-7; recombinant human granulocyte colony-stimulating factor 300 μg, days 1-7). The efficacy was evaluated, adverse reactions during treatment were recorded, and the survival status of the patients was analyzed. Results: A total of 28 eligible patients were included, among whom 13 were male and 15 were female, with a male-to-female ratio of 0.86:1. The median age was 55.5 years (range: 18-75 years). The proportions of FAB subtypes were as follows: M1 14.3% (4/28), M2 46.4% (13/28), M4 32.1% (9/28), and M5 7.1% (2/28). In terms of risk stratification at initial diagnosis, the favorable risk group accounted for 32.1% (9/28), the intermediate risk group for 28.6% (8/28), and the poor risk group for 39.3% (11/28). Among them, 3 patients had AML1/ETO at initial diagnosis, 3 had CBFβ/MYH11, and 1 had BCR/ABL 190 fusion gene, and this patient received dasatinib/imatinib during induction therapy. All the above patients completed 1 course of treatment, 21.4% (6 cases) completed 2 courses, with a median number of treatment courses of 1 (range: 1-2). The complete remission (CR) rate after 1 course was 67.9% (19/28), including a CR with incomplete recovery rate of (4/28), a CR with partial recovery rate of (3/28), and Minimal Residual Disease negative rate of 73.7% (14/19), non-response rate of 28.6% (8/28), and 1 patient was undergoing efficacy evaluation. The 6 patients who completed 2 courses of treatment remained in CR status after the 2nd course, but 1 of them had MRD turned positive. The incidence of hematological adverse reactions during treatment was 100%. Non-hematological adverse reactions included: infection 42.9% (12/28), febrile neutropenia 42.9% (12/28), bleeding 42.9% (12/28), pneumonia 32.1% (9/28), oral ulcer 10.7% (3/28), sepsis 7.1% (2/28) (pathogens were Escherichia coli, Ralstonia mannitolilytica, Aspergillus flavus, and Aspergillus fumigatus respectively), non-infectious diarrhea (1/28), liver dysfunction (1/28), herpes labialis (1/28), tuberculosis (1/28), disseminated intravascular coagulation and chronic osteomyelitis (1/28). Among the 28 included patients, 21 are currently alive, with a median overall survival (OS) of 4 months (1-9). The estimated 6-month survival rate is 67% (95% CI: 37.7% - 84.9%). Conclusion: This prospective study confirms that the combination of azacitidine, venetoclax and GHA priming regimen can be an effective induction remission regimen for patients with refractory/relapsed acute myeloid leukemia, with high safety and good tolerance, which is worthy of further verification with an expanded sample size.