Ven-based therapy vs HMA monotherapy in ND AML: A PETHEMA AML registry study

Results from a retrospective, multicenter PETHEMA AML registry study (NCT02607059) comparing venetoclax (Ven)-based therapy vs hypomethylating agent (HMA) monotherapy in patients with newly diagnosed (ND) acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC) were published in Leukemia by Aspas Requena et al. The primary endpoint was overall survival (OS). 

Key data: At a median follow-up of 25.3 months, median OS was 11.4 months with Ven-based therapy (n = 929) vs 8.2 months with HMA monotherapy (n = 1,681; hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.60–0.73; p < 0.001). In exploratory subgroup analyses, median OS was longer with Ven-based therapy vs HMA monotherapy in patients with IDH1-mutated (IDH1m; p = 0.011), IDH2-mutated (IDH2m; p < 0.001), NPM1-mutated (NPM1m; p < 0.001), and FLT3-internal tandem duplication (ITD; p < 0.001) AML. No significant OS benefit with Ven-based therapy vs HMA monotherapy was observed in patients with AML arising from myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN). 

Key learning: In this real-world study, Ven-based therapy was associated with improved OS vs HMA monotherapy in patients with ND AML ineligible for IC. The varied magnitude of OS benefit observed across molecular subgroups suggests that molecular characteristics may help inform treatment selection; however, further evaluation is needed.