Venetoclax-Decitabine Non-Inferior to Intensive Chemotherapy in Young AML Patients
A randomized trial in 188 AML patients aged 18-59 showed venetoclax plus decitabine achieved 89% composite complete remission versus 79% with standard idarubicin-cytarabine, with superior results in adverse-risk and epigenetic-mutation subgroups. MRD negativity rates were high in both arms, emphasizing the growing role of flow cytometry and molecular MRD assays in treatment response assessment.
The original study
Venetoclax and decitabine vs intensive chemotherapy as induction for young patients with newly diagnosed AML.
- Authors
- Lu J, Xue SL, Wang Y, He XF, Hu XH, Miao M, et al.
- Journal
- Blood
- Type
- Journal Article, Randomized Controlled Trial, Multicenter Study, Comparative Study
- PMID
- 40009498
Original abstract
Venetoclax (VEN) combined with hypomethylating agents is approved for frontline therapy in older/unfit patients with acute myeloid leukemia (AML). However, prospective data on this low-intensity therapy in treatment-naive younger patients with AML are lacking. This study investigated the efficacy and safety of VEN plus decitabine (VEN-DEC) as induction in untreated young fit patients with AML in a randomized trial. Patients aged 18 to 59 years eligible for intensive chemotherapy were randomized 1:1 to receive VEN-DEC or IA-12 (idarubicin and cytarabine). All patients achieved composite complete remission (CRc) underwent high-dose cytarabine consolidation. The primary end point was CRc rate after induction. 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 vs 79% (74/94) in the IA-12 group (noninferiority P = .0021), with measurable residual disease negativity rates of 80% (67/84) vs 76% (56/74), respectively. VEN-DEC showed superior CRc in patients aged ≥40 years (91% vs 75%) and those with adverse risk (91% vs 42%) or epigenetic mutations (91% vs 67%), but lower CRc in RUNX1::RUNX1T1 fusion cases (44% vs 88%) than 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 < .001). At a median follow-up of 12.1 months, overall and progression-free survival were similar between groups. In conclusion, VEN-DEC demonstrated noninferior response rates with superior safety over IA-12 in young patients with AML. The trial was registered at www.clinicaltrials.gov as #NCT05177731.