Comparable Short Term Outcomes Among Patients with Newly Diagnosed Acute Myeloid Leukemia with or without Myelodysplasia Related Gene Mutations Treated with Azacytidine-Venetoclax: Observations from a Single Center Retrospective Cohort.

Acute Myeloid Leukemia (AML) is a heterogeneous hematologic malignancy, and up to 50% of cases are classified as cytogenetically normal AML (CNAML). The 2022 European Leukemia Net (ELN) guidelines identify Myelodysplasia Related(MR) gene mutations, such as ASXL1 and RUNX1, as adverse risk factors, particularly in patients treated with intensive chemotherapy. However, limited data exist regarding the prognostic impact of MR mutations in CN-AML patients managed with Azacytidine and Venetoclax (Aza+Ven) based induction. In the current study, consecutive patients with newly diagnosed CN- AML treated at one centre were classified as MR positive and negative on the basis of the presence and absence of MR mutations respectively. Clinical data, including patient demographics and treatment onsecutivet responses, were systematically recorded, and the cytogenetic and molecular data were analyzed to correlate these findings with clinical outcomes, such as complete remission rates and overall survival. Fifty three consecutive newly diagnosed AML patients treated with Aza+Ven were screened. Thirty two patients having CN-AML were included in the current analysis. The CR/CRi rates were comparable between MR mutated and MR unmutated groups (80% vs. 70%, p=0.5). The proportion of patients attaining MRD negativity after the first cycle was not significantly different [MR mutated (3/10, 30%) versus MR unmutated (7/22, 31%); (P = 0.95)] amongst the two groups. Median progression-free survival (PFS) and overall survival (OS) was not significantly different between MR mutated and MR unmutated groups (not reached vs. 12 months, p=0.437 and p=0.136,; HR-0.53, 0.22;p-0.45,0.17 respectively). Our findings, support that the presence of MR mutations may not adversely impact treatment outcomes when treated with Aza+Ven treatment regimen.