Venetoclax and Hypomethylating Agent Treatment Shows Efficacy for R/R Acute Myeloid Leukemia, With Genetic Predictors of Response Identified

Venetoclax plus hypomethylating agents demonstrated efficacy for treating relapsed/refractory (R/R) acute myeloid leukemia (AML) and genetic features among patients may be used as predictors of response, according to results from a single-center retrospective study published in Cancers.

Venetoclax plus hypomethylating agents have been used for patients with relapsed/refractory AML, however research is limited on its efficacy and potential predictors of response among patients. Researchers sought to determine the impact of venetoclax plus hypomethylating agents on patient outcomes, as well as determine clinical and molecular predictors of response.

In total, 197 patients with R/R AML who previously received treatment with venetoclax plus hypomethylating agents were enrolled. Next-generation sequencing of 139 genes was used to conduct molecular profiling of all enrolled patients to determine predictors and potential response.

Overall, the median follow-up was 14 months (range, 0.7 to 54) the complete remission rate, including complete remission and incomplete hematologic recovery, was 44.7%. The overall response rate was 59.9%, with a 1-yearOS at 55.4% and a 2-year OS at 40.2%. Patients who had the CBFB-MYH11 fusion gene, NPM1, and/or IDH1 or IDH2 mutations demonstrated better OS rates, while patients with FLT3-ITD, TP53, DNMT3A, and GATA2 had lower OS rates.

In terms of predictors of response, the researchers found that mutations in NPM1 and SRSF2 demonstrated improved response rates, while GATA2 mutations were associated with lower response rates, compared to patients without these mutations. Additionally, patients who were previously exposed to hypomethylating agents and/or had early relapse demonstrated lower response rates.

“The VEN + HMAs regimen demonstrated considerable efficacy in the treatment of R/R AML patients, with both response rates and overall survival being influenced by distinct genetic features,” the researchers concluded, adding, “these findings provide valuable insights into optimizing personalized treatment strategies for this challenging patient population.

Source:

Wang L, Gao H, Fu Q, et al. Clinical and Molecular Predictors of Response and Survival Following Venetoclax Plus Hypomethylating Agents in Relapsed/Refractory Acute Myeloid Leukemia: A Single-Center Study in Chinese Patients. Cancers. Published online February 8, 2025. doi: 10.3390/cancers17040586