Unveiling prognosis in patients with acute myeloid leukemia treated with hypomethylating agents and venetoclax through novel risk stratification.

Several genetic risk classification systems based on response to older acute myeloid leukemia patients treated with less-intensive regimens, especially venetoclax (VEN) + hypomethylating agent (HMA), are proposed recently. VEN+HMA improved the outcome of cytogenetic adverse-risk AML, AML with some of MR mutations and/or clonal hematopoiesis (CH) related mutations. DNMT3A mut, IDH1/2 mut and NPM1 mut were defined as "VEN sensitive mutations". DDX41 mut is identified as a particularly favorable-risk group. Even multi-hit TP53 status did not negatively affect overall survival (OS) of DDX41-mutants. Signaling gene mutations (FLT3-ITDpos and K/NRAS mut) are classified as intermediate risk, consistent with their biological associations as mediators of VEN resistance.