{"entity":{"id":"venetoclax-plus-hma","kind":"pairing","name":"Venetoclax + hypomethylating agent","aka":[],"tldr":"Azacitidine primes leukaemia cells for death; venetoclax removes the BCL-2 shield. Together they roughly doubled remissions in older AML.","summary":"This combination pairs venetoclax with the hypomethylating agent azacitidine in acute myeloid leukaemia, chiefly in older patients who cannot have intensive chemotherapy. Azacitidine lowers MCL-1 and induces NOXA, which increases the leukaemia cells' dependence on BCL-2, and venetoclax then blocks BCL-2 and removes that last shield, driving intrinsic apoptosis. The phase 3 VIALE-A trial showed an overall survival benefit and a higher remission rate than azacitidine alone, and the regimen is now available fully orally with decitabine-cedazuridine plus venetoclax, supported by ASCERTAIN-V and introduced in 2026. The duration of venetoclax within each cycle is being shortened from 28 days to 14 to reduce cytopenias without losing efficacy.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02993523: VIALE-A","url":"https://clinicaltrials.gov/study/NCT02993523"},{"label":"ClinicalTrials.gov NCT04657081: ASCERTAIN-V","url":"https://clinicaltrials.gov/study/NCT04657081"}],"tags":[],"related":[],"cancers":["aml"],"sections":[],"technologies":[],"targets":[],"drugs":["venetoclax","azacitidine","decitabine-cedazuridine"],"companies":[],"institutions":[],"pathways":["apoptosis-bcl2"],"terms":[],"trials":["viale-a","ascertain-v"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"venetoclax","b":"azacitidine","rationale":"Azacitidine lowers MCL-1 and induces NOXA, increasing dependence on BCL-2, which venetoclax then blocks.","evidence":"Phase 3 (VIALE-A) OS benefit; ASCERTAIN-V for the oral backbone.","pairingType":"combination"},"route":"/pairings/venetoclax-plus-hma/","neighbours":{"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/"}],"drug":[{"id":"azacitidine","kind":"drug","name":"Azacitidine","route":"/drugs/azacitidine/"},{"id":"decitabine-cedazuridine","kind":"drug","name":"Decitabine + cedazuridine (oral)","route":"/drugs/decitabine-cedazuridine/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"}],"pathway":[{"id":"apoptosis-bcl2","kind":"pathway","name":"Intrinsic apoptosis (BCL-2 family)","route":"/pathways/apoptosis-bcl2/"}],"trial":[{"id":"ascertain-v","kind":"trial","name":"ASCERTAIN-V","route":"/trials/ascertain-v/"},{"id":"viale-a","kind":"trial","name":"VIALE-A","route":"/trials/viale-a/"}],"paper":[{"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","route":"/key-papers/paper-viale-a-venetoclax-azacitidine-nejm-2020/"}]}}