Venetoclax Plus Hypomethylating Agent Treatment Shows Promise for Patients With Mutated AML
Venetoclax in combination with hypomethylating agents (HMAs) demonstrated promising efficacy and safety among patients with FLT3-mutated and IDH1/2-mutated acute myeloid leukemia (AML), while demonstrating an important need for monitoring and managing adverse events, according to study results published in European Journal of Medical Research.
Venetoclax in combination with hypomethylating agents have demonstrated efficacy for treating AML, however research is limited on the impact of venetoclax and HMAs among patients with an FLT3- or IDH1/2-mutated AML. Researchers sought to determine the efficacy and safety of a treatment of venetoclax plus hypomethylating agents in a systematic review and meta-analysis.
Overall, 20 studies were included which included 1640 patients with newly diagnosed or relapsed/refractory (R/R) AML treated with venetoclax-HMA therapy.
Among all patients, the overall response (OR) rate was 57% (95% confidence interval [CI], 0.50 to 0.64; I2= 79%; P < .01). The OR rate was higher for patients who had R/R AML (0.68; 95% CI, 0.54 to 0.80; I2= 27%; P= .25) compared with patients who were previously untreated (0.56; 95% CI, 0.46 to 0.67; I2= 73%; P < .01).
The pooled complete remission (CR) rate was 0.52 (95% CI, 0.44 to 0.60; I2= 84%; P= < .01). Subgroup analysis demonstrated patients with IDH mutations achieved the highest CR rate (0.71; 95% CI, 0.63 to 0.79; I2= 22%; P = .27), followed patients with FLT-3 mutations (0.64; 95% CI, 0.43 to 0.82; I2= 54%; P = .06). Patients with TP53-mutated AML, had the lowest CR rate of any patient subgroup (0.44; 95% CI, 0.32 to 0.57; I2= 0%; P = .53).
In terms of safety, the pooled adverse event rate grade 3 or higher was 0.83 (95% CI, 0.57 5o 0.98; I2= 27%; P= .25 I2= 95%; P < .01). The most frequently reported adverse events were anemia (0.31; 95% CI, 0.11 to 0.55; I2= 95%; P < .01), neutropenia (0.51; 95% CI, 0.27 to 0.76; I2= 96%; P< .01), and thrombocytopenia (0.49; 95% CI, 0.30 to 0.69; I2= 95%; P< .01).
“Our study provides comprehensive insights into the efficacy and safety of venetoclax and HMAs in AML treatment, particularly in patients with FLT-3 and IDH mutations,” the researchers concluded.
They added, “the findings underscore the potential benefits of this therapeutic approach while emphasizing the need for further research, including prospective studies and well-designed RCTs, to optimize the clinical use of venetoclax and minimize associated toxicities.”
Source:
Wang Y, Chen Y, Ji D, et al. Meta-analysis on the effectiveness and safety of venetoclax-based combination therapy with hypomethylation in acute myeloid leukemia. European Journal of Medical Research. Published online April 26, 2025. doi:10.1186/s40001-025-02571-x
