Venetoclax and Decitabine vs Intensive Chemotherapy as Induction for Young Patients with Newly Diagnosed AML

• VEN-DEC showed not inferior response to IA-12 in young/fit untreated AML patients.

• VEN-DEC had fewer SAEs and shorter severe thrombocytopenia duration than IA-12.

Venetoclax combined with hypomethylating agents is approved for frontline therapy in older/unfit acute myeloid leukemia (AML) patients. However, prospective data on this low intensity therapy in treatment-naive younger AML patients are lacking. This study investigated the efficacy and safety of venetoclax plus decitabine (VEN-DEC) as induction in untreated young fit AML patients in a randomized trial. Patients aged 18-59 years eligible for intensive chemotherapy were randomized 1:1 to receive VEN-DEC or IA-12 (idarubicin and cytarabine). All patients achieving CR/CRi underwent high-dose cytarabine consolidation. The primary endpoint was the composite complete remission rate (CRc) rate after induction therapy. Of 255 screened, 188 were enrolled and randomly assigned, with 94 in each group. In the intention-to-treat population, CRc was 89% (84/94) in the VEN-DEC group versus 79% (74/94) in IA-12 (non-inferiority P = 0.0021). MRD negativity after induction was 80% (67/84) versus 76% (56/74), respectively. VEN-DEC showed superior CRc in patients aged ≥40 years (91% vs. 75%), those with adverse risk (91% vs. 42%) or epigenetic mutations (91% vs. 67%) , but lower CRc in RUNX1::RUNX1T1 fusion cases (44% vs. 88%) compared to IA-12. Patients in the VEN-DEC group experienced fewer grade ≥3 infections (32% vs. 67%) and shorter severe thrombocytopenia duration (median 13 vs. 19 days, P < 0.001). At a median follow-up of 12.1 months, overall and progression-free survival were similar between groups. In conclusion, VEN-DEC demonstrated non-inferior response rates with superior safety over IA-12 in young AML patients. The trial was registered at ClinicalTrials.gov as #NCT05177731.