# Venetoclax + hypomethylating agent

Source: https://onco.cc/pairings/venetoclax-plus-hma/  
OnCo record `venetoclax-plus-hma` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Venetoclax + Azacitidine
- Type: combination
- 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.

## Sources

- ClinicalTrials.gov NCT02993523: VIALE-A: https://clinicaltrials.gov/study/NCT02993523
- ClinicalTrials.gov NCT04657081: ASCERTAIN-V: https://clinicaltrials.gov/study/NCT04657081

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Acute myeloid leukaemia in older or unfit patients](https://onco.cc/cancers/aml-older-unfit/)
- drugs: [Azacitidine](https://onco.cc/drugs/azacitidine/), [Decitabine + cedazuridine (oral)](https://onco.cc/drugs/decitabine-cedazuridine/), [Venetoclax](https://onco.cc/drugs/venetoclax/)
- pathways: [Intrinsic apoptosis (BCL-2 family)](https://onco.cc/pathways/apoptosis-bcl2/)
- trials: [ASCERTAIN-V](https://onco.cc/trials/ascertain-v/), [VIALE-A](https://onco.cc/trials/viale-a/)
- key papers: [VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy](https://onco.cc/key-papers/paper-viale-a-venetoclax-azacitidine-nejm-2020/)

---
JSON: https://onco.cc/api/v1/entities/venetoclax-plus-hma.json