Exploring Prognostic Factors of Venetoclax Combined with Azacitidine in Unfit AML Based on Real-World Data from a Chinese Population

Background: Venetoclax combined with azacitidine (VA) has become the standard first-line treatment for elderly unfit acute myeloid leukemia (AML) patients. In the era of targeted therapy, it is essential to explore new prognostic factors. Objective: To investigate the factors influencing overall survival (OS) in newly diagnosed unfit AML (ND unfit AML) patients induced with VA, and in unfit AML patients who achieved composite complete remission (cCR unfit AML) and received VA maintenance therapy. Methods: We retrospectively analyzed the clinical data of 112 ND unfit AML at Sichuan Provincial People's Hospital from January 2022 to May 2024. We observed treatment efficacy and survival outcomes, and utilized the COX regression model for statistical analysis to identify influencing factors. Results: The median age of the included patients was 68 years (range: 43-86), with 57 male patients (51%). Eleven patients (10%) had secondary AML, and 81 patients (72%) had an ECOG score of 0-1. According to ELN-2022 cytogenetic risk stratification, 21 patients (19%) were low-risk, 44 patients (39%) were intermediate-risk, and 47 patients (42%) were high-risk. The cCR rate in ND unfit AML patients was 79% (including 24% CR and 55% CRi), with an MRD negativity rate of 47%. Seven patients (6%) received allogeneic transplantation after remission. The median follow-up was 16.2 months (95% CI: 14.7-17.7), and the median OS was 12.9 months (95% CI: 8.0-17.8). Patients who achieved cCR had a significantly longer median OS compared to incomplete remission (IR) (42.4 months vs. 2.0 months, p<0.0001). There was no significant difference in survival curves among different ELN risk stratifications (NR vs. 12.1 months vs. 11.2 months, p = 0.3150). Among cCR unfit AML patients, those with MRD negativity had significantly better OS compared to those without MRD negativity (NR vs. 8.7 months, p<0.0001). COX regression analysis indicated that IR, MRD positivity, t(8;21)(q22;q22)/AML1-ETO positivity, U2AF1 mutation, and post-treatment ECOG (＞1) were independent adverse prognostic factors in ND unfit AML patients. For cCR unfit AML patients, MRD positivity, U2AF1 mutation, and post-treatment ECOG (＞1) were independent adverse prognostic factors. Conclusion: The VA regimen is effective in treating unfit AML patients. Patient OS is influenced by treatment response, performance status, and cytogenetic factors.