Venetoclax and hypomethylating agents versus other therapies: an international, multicenter, retrospective cohort chart review study

Venetoclax (VEN) plus hypomethylating agents (HMA) is approved for newly diagnosed (ND) acute myeloid leukemia (AML) in patients ineligible for intensive chemotherapy (IC). This international retrospective chart review involving 17 academic sites included 576 adults with ND AML treated with VEN+HMA and matched controls who received non-VEN regimens (11/2019-08/2024). VEN+HMA patients were matched 1:1 to controls by age and European LeukemiaNet 2017 risk. Of 288 VEN+HMA patients, 192 were IC-ineligible (≥75 years or ≥1 comorbidity). Compared to controls receiving high- or low-intensity regimens, IC-ineligible VEN+HMA patients had significantly higher composite complete remission rates (63.7% vs. 46.0%; p < 0.01) and numerically higher median overall survival (17.4 [95% CI: 13.3-21.0] vs. 13.6 [95% CI: 10.5-15.9] months) and transfusion independence rates (63.7% vs. 53.2%). Similar trends were observed in subgroups aged ≥75 and ≥80 years. These findings reinforce the clinical effectiveness of VEN+HMA as a frontline regimen for IC-ineligible patients with AML.