[Comparison of the efficacy and safety of venetoclax plus azacitidine versus D-CAG regimen in the treatment of elderly patients with relapsed or refractory acute myeloid leukemia].

Objective: To compare the efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) (VA) versus decitabine combined with cytarabine+aclarubicin+granulocyte colony-stimulating factor (CAG) (D-CAG) regimen in the treatment of elderly patients with relapsed or refractory acute myeloid leukemia (RR-AML) . Methods: This prospective randomized study was conducted using VA and D-CAG regimens for the salvage treatment of elderly patients with RR-AML. A sealed envelope was used for randomization, with a planned enrollment of 50 patients. The primary endpoints were objective response rate (ORR) and composite complete remission (cCR) rate, whereas the secondary endpoints included overall survival (OS), duration of remission (DOR), and safety. Results: From January 2021 to June 2024, 50 elderly patients with RR-AML received at least one cycle of either VA or D-CAG treatment and completed efficacy and safety assessments. The VA group comprised 22 patients with a median age of 63.0 (range: 60.8-69.3) years, and the D-CAG group included 28 patients with a median age of 66.5 (range: 62.3-69.0) years. DNA methylation gene mutations were the most frequent, comprising 8 cases (36.4%) in the VA group and 9 cases (32.1%) in the D-CAG group. The ORR was 68.2% (15/22) and 53.6% (15/28) and the cCR rate was 68.2% (15/22) and 46.4% (13/28) in the VA and D-CAG groups, respectively. No significant difference in ORR or cCR was observed between the two groups. Subgroup analysis revealed that the cCR rate in the VA group with AML-MR gene mutations was 6/7, which was higher than 4/10 in the D-CAG group. Patients were categorized into early relapse, late relapse, and refractory groups. The cCR rate for early relapse was below 40% with both regimens. In the late relapse group, 4 of 5 patients in the VA group achieved cCR, and both patients in the D-CAG group achieved cCR. The median follow-up time was 19 months (IQR: 11-48.5 months). The median OS was 16 months in the whole cohort, with 19 months for the VA group and 11 months for the D-CAG group (P=0.189). Among the 30 patients who achieved cCR after salvage chemotherapy (VA=15 and D-CAG=15), the DOR in the VA group demonstrated a significant advantage over that in the D-CAG group (not reaching vs 6 months, P=0.023). The median OS for the early relapse, late relapse, and refractory groups was 5, 21, and 18 months, respectively, with significantly better efficacy observed in the late relapse group (P=0.020). Four patients who received salvage treatment followed by allogeneic stem cell transplantation had no evidence of disease, demonstrating a survival advantage compared with nontransplant patients (P=0.007). The incidence of rash (27.3% vs 3.6%, P=0.047) and diarrhea (40.9% vs 7.1%, P=0.012) in the VA group was significantly higher than that in the D-CAG group. Conclusion: The VA and D-CAG regimens have comparable efficacy for elderly patients with RR-AML. Patients with late relapse demonstrated better efficacy with both regimens compared with the early relapse and refractory groups.