# VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy

Source: https://onco.cc/key-papers/paper-viale-a-venetoclax-azacitidine-nejm-2020/  
OnCo record `paper-viale-a-venetoclax-azacitidine-nejm-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2020
- DOI: 10.1056/NEJMoa2012971
- Authors: DiNardo CD, Jonas BA, Pullarkat V, et al.
- Findings: 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.
- What it means: 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.
- Caveats: 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.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa2012971
- ClinicalTrials.gov NCT02993523: https://clinicaltrials.gov/study/NCT02993523

## Connected records

- pairings: [Menin inhibitor + venetoclax + azacitidine](https://onco.cc/pairings/menin-plus-venetoclax-hma/), [Venetoclax + hypomethylating agent](https://onco.cc/pairings/venetoclax-plus-hma/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Acute myeloid leukaemia in older or unfit patients](https://onco.cc/cancers/aml-older-unfit/), [Secondary and therapy-related acute myeloid leukaemia](https://onco.cc/cancers/aml-secondary/)
- targets: [BCL-2](https://onco.cc/targets/bcl2/)
- drugs: [Azacitidine](https://onco.cc/drugs/azacitidine/), [Venetoclax](https://onco.cc/drugs/venetoclax/)
- companies: [AbbVie (incl. ImmunoGen, Capstan)](https://onco.cc/companies/abbvie/)
- institutions: [MD Anderson Cancer Center](https://onco.cc/institutions/md-anderson/)
- terms: [MRD-negative complete remission](https://onco.cc/terms/mrd-negative-cr/), [Overall survival (OS)](https://onco.cc/terms/os/)
- trials: [VIALE-A](https://onco.cc/trials/viale-a/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Older and multimorbid patients are excluded and undertreated](https://onco.cc/bottlenecks/b-aging-comorbidity/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- ideas: [Shorter venetoclax courses in unfit AML](https://onco.cc/ideas/idea-shortened-venetoclax/)
- people: [Courtney D. DiNardo](https://onco.cc/people/courtney-dinardo/)
- key papers: [AGILE: ivosidenib plus azacitidine for newly diagnosed IDH1-mutated AML in patients unfit for intensive chemotherapy](https://onco.cc/key-papers/paper-agile-ivosidenib-azacitidine-nejm-2022/)
- roadmaps: [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/)

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