The Efficacy and Survival Analysis of Fit-AML Patients Treated with Venetoclax Combined with Hypomethylating Agents (VEN-HMAs)
Authors: Zhang Ludan , Sui Jingchen , Wang Pingping , Pan Deng , Yan Xiaojing 
Published: December 2024

Introduction: Traditional induction therapy regimens for elderly patients with acute myeloid leukemia (AML) often show low efficacy (33.3%) and high early mortality rates (10.6%). The 5-year overall survival (OS) rate of AML patients aged 60 to 65 years is &lt;25%. According to guidelines, the treatment options of standard chemotherapy or VEN-HMAs for AML patients aged 60-75 years are not yet clear. Therefore, in clinical practice, some elderly AML patients who could tolerate standard-dose chemotherapy (Fit-AML) were treated with VEN-HMAs. To explore effective treatment options, we retrospectively analyzed the efficacy and survival outcomes of elderly Fit-AML patients treated with the VEN-HMAs, as well as the predictive factors influencing treatment response and survival duration.
Methods: We collected clinical data from 75 newly diagnosed Fit-AML patients treated at the First Affiliated Hospital of China Medical University between March 2020 and April 2024, who received the VEN-HMAs regimen. Diagnosis was based on the 2016 World Health Organization criteria, and risk stratification followed the 2022 European Leukemia Net recommendations. Adverse events (AEs) were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events (CTCAE). Data analysis and visualization were performed using SPSS 22.0, R, and GraphPad Prism 8. Categorical data were compared using the χ² test. Kaplan-Meier curves were used for survival analysis, with the log-rank test for univariate analysis. A P value &lt; 0.05 was considered statistically significant. The study evaluated the patients' treatment responses, survival status, and adverse events throughout the treatment period.
Results: 1. Evaluation of treatment response: Following VEN-HMAs treatment, the complete remission/complete remission with incomplete hematological recovery (CR/CRi) rate was 55/75 (73.3%) and the negative minimal residual disease (MRD-) rate was 39/55 (71.0%). The early mortality (within 30 days) rate of 8.8%. The following treatment and long-term survival: 7 patients switched to intensive chemotherapy after induction remission of VEN-HMAs and 3 patients received hematopoietic stem cell transplantation after achieving remission. The others kept on the VEN-HMAs regimen until disease progression or intolerance. Median follow-up time was 12 months, and the median overall survival (mOS) was 15 months, and a median relapse-free survival (mRFS) was 7 months (Figure 1).According to the ELN 2022, patients were categorized into favorable (20 cases), intermediate (18 cases), and adverse (37 cases). There was no statistically significant difference in the short-term efficacy among patients with different risk stratifications (P = 0.979). The CR/CRi rate was 75.0% (15/20) in the good prognosis group, 72.2% (13/18) in the moderate prognosis group, and 72.9% (27/37) in the poor prognosis group. However, survival analysis revealed statistically significant difference in different risk stratifications (P = 0.007). The genetic alterations of all the patients were listed in Figure 2.
Conclusion: The VEN-HMAs regimen demonstrates good short-term and long-term efficacy in Fit-AML patients in a single center. Furthermore, while there is no significant difference in short-term efficacy among different prognostic stratifications, patients with favorable prognosis exhibit a significantly longer survival time.