VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy
Adding the BCL-2 inhibitor venetoclax to azacitidine more than doubled remission rates and extended median survival from 9.6 to 14.7 months in unfit AML patients.
VIALE-A randomised 431 patients with newly diagnosed AML who were ineligible for intensive induction (median age 76) in a 2:1 ratio to azacitidine plus venetoclax or azacitidine plus placebo. Primary endpoints were overall survival and composite complete remission. Median OS was 14.7 versus 9.6 months (hazard ratio 0.66); complete remission was 36.7% versus 17.9% and complete remission with incomplete count recovery 66.4% versus 28.3%, with responses achieved faster and more often MRD-negative. Febrile neutropenia (42% versus 19%) and infections were more frequent with venetoclax. The regimen became the global standard for unfit AML.
- 431 patients unfit for intensive chemotherapy, median age 76; azacitidine + venetoclax vs azacitidine + placebo (2:1).
- Median OS 14.7 vs 9.6 months; hazard ratio 0.66.
- Complete remission 36.7% vs 17.9%; CR + CRi 66.4% vs 28.3%.
- Responses were faster (median 1.3 months to first response) and more often MRD-negative.
- Febrile neutropenia 42% vs 19%; grade 3 or higher infections more frequent.
VIALE-A turned a palliative regimen into one that produces remission in two-thirds of older AML patients and is now the reference treatment for anyone not fit for intensive chemotherapy. It shifted the field towards lower-intensity targeted combinations and opened the door to adding FLT3, IDH and menin inhibitors to the backbone. Cure remains uncommon and most patients relapse within two years.
- Median survival gain was about five months; long-term survival is still poor.
- Benefit was smaller in TP53-mutated and adverse-karyotype disease.
- Prolonged cytopenias require dose interruptions and expertise; real-world outcomes are worse than trial results.
- No comparison against intensive chemotherapy in fit patients.