Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with a genetic variability that plays a role in determining clinical outcomes. The 2022 European LeukemiaNet (ELN) model uses molecular data to stratify risk in patients receiving high-intensive induction with or without allogeneic hematopoietic stem cell transplantation (allo-SCT), however, its predictive value is limited in those treated with less-intensive induction (Venetoclax plus hypometilating agents-HMA). Due to this gap, a 2024 model based mostly on VIALE-A study stratified patients into three groups:(1) TP53 mutations are classified as adverse risk;(2) mutations in FLT3-ITD, NRAS, or KRAS, or other mutations not classified as favorable or adverse, are intermediate risk; and(3) the presence of NPM1, IDH1, IDH2 or DDX41– or the absence of intermediate or adverse risk changes are considered favorable-risk. Yet, this remains suboptimal considering that mutations classified as adverse in ELN2022 may not carry the same poor prognostic impact in patients treated with less-intensive induction. Also, HMA plus Venetoclax is now used in a more heterogeneous population than in VIALE-A.

Evaluate risk reclassification by mutation profiles and the impact in treatment response and outcomes in AML patients receiving less-intensive induction in a brazilian Center.

A retrospective analysis was made with electronic medical records of patients diagnosed with AML in our center that received induction with Venetoclax and Azacytidine and had molecular biology evaluated by next-generation sequencing (NGS) or Fluorescence In Situ Hybridization.

We included 29 patients with AML diagnosed between 2018-2024. The median age was 70 years, with a male predominance (62%). 16 patients (55%) were classified as eligible for allo-SCT. 7 patients (24%) were therapy-related AML and 12(41%) were considered as a secondary progression from Myelodysplastic Syndrome. The most frequent mutations identified were TP53(26%) and ASXL1(24%), mutations in IDH2, SRSF2, and STAG2 were each detected in 21% of cases.According to the ELN2022, 25 patients (86%) were classified as adverse-risk, 3 (10%) as intermediate-risk, and only 1 (3%) as favorable-risk. However, based on the ELN2024, 17 patients (59%) were reclassified as intermediate-risk, 8 (26%) as adverse-risk, and 4 (14%) as favorable-risk. 1 case initially categorized as intermediate-risk by ELN2022 was reclassified as favorable-risk by the ELN2024, and 15 patients originally assigned to the adverse-risk group were reclassified as intermediate-risk. Risk classification remained unchanged in only 11 cases (38%). 23 patients (79%) achieved a hematologic response, of which 14 presented negative measurable residual disease, the majority (64%) after the first cycle. Only 3 patients (10%) were refractory to treatment, one of them still alive at last follow-up.15 patients underwent allo-SCT as consolidation therapy.At their last follow-up,6 patients relapsed, 3 during treatment and 3 post allo-SCT, 9 maintained response, 15 patients (52%) died and 4 cases were lost at follow-up. The median time from diagnosis to relapse was 8.3 months, and 2.7 months between relapse and death, with a follow up of 11.1 months from diagnosis to death.

In a developing country hospital without routine NGS access, accurate molecular classification is limited, and reaching a large sample of patients can be challenging, demonstrating the importance of adequate risk stratification for these patients.