{"entity":{"id":"paper-viale-a-venetoclax-azacitidine-nejm-2020","kind":"paper","name":"VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2012971"},{"label":"ClinicalTrials.gov NCT02993523","url":"https://clinicaltrials.gov/study/NCT02993523"}],"tags":[],"related":["venetoclax-plus-hma","menin-plus-venetoclax-hma"],"cancers":["aml"],"sections":[],"technologies":[],"targets":["bcl2"],"drugs":["venetoclax","azacitidine"],"companies":["abbvie"],"institutions":["md-anderson"],"pathways":[],"terms":["os","mrd-negative-cr"],"trials":["viale-a"],"people":[],"bottlenecks":["b-aging-comorbidity","b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa2012971","authors":"DiNardo CD, Jonas BA, Pullarkat V, et al.","paperType":"rct","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."],"whatItMeans":"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."],"changedPractice":true,"participants":431},"route":"/key-papers/paper-viale-a-venetoclax-azacitidine-nejm-2020/","neighbours":{"pairing":[{"id":"menin-plus-venetoclax-hma","kind":"pairing","name":"Menin inhibitor + venetoclax + azacitidine","route":"/pairings/menin-plus-venetoclax-hma/"},{"id":"venetoclax-plus-hma","kind":"pairing","name":"Venetoclax + hypomethylating agent","route":"/pairings/venetoclax-plus-hma/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-older-unfit","kind":"cancer","name":"Acute myeloid leukaemia in older or unfit patients","route":"/cancers/aml-older-unfit/"},{"id":"aml-secondary","kind":"cancer","name":"Secondary and therapy-related acute myeloid leukaemia","route":"/cancers/aml-secondary/"}],"target":[{"id":"bcl2","kind":"target","name":"BCL-2","route":"/targets/bcl2/"}],"drug":[{"id":"azacitidine","kind":"drug","name":"Azacitidine","route":"/drugs/azacitidine/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"}],"company":[{"id":"abbvie","kind":"company","name":"AbbVie (incl. ImmunoGen, Capstan)","route":"/companies/abbvie/"}],"institution":[{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"}],"term":[{"id":"mrd-negative-cr","kind":"term","name":"MRD-negative complete remission","route":"/terms/mrd-negative-cr/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"}],"trial":[{"id":"viale-a","kind":"trial","name":"VIALE-A","route":"/trials/viale-a/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-aging-comorbidity","kind":"bottleneck","name":"Older and multimorbid patients are excluded and undertreated","route":"/bottlenecks/b-aging-comorbidity/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"id":"idea-shortened-venetoclax","kind":"idea","name":"Shorter venetoclax courses in unfit AML","route":"/ideas/idea-shortened-venetoclax/"}],"person":[{"id":"courtney-dinardo","kind":"person","name":"Courtney D. DiNardo","route":"/people/courtney-dinardo/"}],"paper":[{"id":"paper-agile-ivosidenib-azacitidine-nejm-2022","kind":"paper","name":"AGILE: ivosidenib plus azacitidine for newly diagnosed IDH1-mutated AML in patients unfit for intensive chemotherapy","route":"/key-papers/paper-agile-ivosidenib-azacitidine-nejm-2022/"}],"roadmap":[{"id":"epigenetics-roadmap","kind":"roadmap","name":"Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome","route":"/roadmaps/epigenetics-roadmap/"}]}}