Longer time from diagnosis to initiation of hypomethylating agents plus venetoclax for acute myeloid leukemia does not worsen survival: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)

A diagnosis of acute myeloid leukemia (AML) has been considered an oncologic emergency. However, the prevailing wisdom to quickly administer AML-directed therapy is often in conflict with the time needed to complete the evaluation of actionable AML disease biology. Previous studies in intensively treated patients reported that time from date of diagnosis to treatment start date (TDT) did not impact survival outcomes. We conducted a US-based, multi-center, retrospective cohort study assessing the impact of TDT on overall survival (OS) in patients with newly diagnosed AML treated with hypomethylating agents (HMA) + venetoclax at eight participating academic centers. Four hundred and eighty-eight patients were included with a median age of 76 years. Patients had favorable (47.6%), intermediate (22.8%), and adverse (29.6%) risk disease by the 2024 European LeukemiaNet (ELN) 2024 less-intensive risk classification. Median TDT for the cohort was 9 days (interquartile range [IQR], 5-17). Those with TDT <14 days (median OS, 8.2 months; 95% confidence interval [CI]: 6.8-9.9) versus ≥14 days (median OS, 11.3 months; 95% CI: 9.5-15.4) had worse OS (P=0.007). TDT ≥14 days was associated with improved OS in multivariable analysis (hazard ratio =0.73, 95% CI: 0.54-0.97; P=0.033) adjusting for age, performance status, use of cytoreductive therapy, white blood cell count at presentation, ELN 2024 less-intensive risk classification, and presence of FLT3-ITD, TP53, and IDH1/2 mutations. These results suggest that stable patients with newly diagnosed AML eventually treated with HMA + venetoclax may await appraisal of disease biology and medical optimization before initiating induction therapy.