# AGILE: ivosidenib plus azacitidine for newly diagnosed IDH1-mutated AML in patients unfit for intensive chemotherapy

Source: https://onco.cc/key-papers/paper-agile-ivosidenib-azacitidine-nejm-2022/  
OnCo record `paper-agile-ivosidenib-azacitidine-nejm-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding the IDH1 inhibitor ivosidenib to azacitidine tripled median survival, from 7.9 to 24 months, in older patients with IDH1-mutated AML.

## Summary

AGILE randomised 146 patients with newly diagnosed IDH1-mutated AML who were ineligible for intensive induction to ivosidenib plus azacitidine or placebo plus azacitidine. The primary endpoint was event-free survival. EFS favoured ivosidenib (hazard ratio 0.33), complete remission was 47% versus 15%, and median overall survival was 24.0 versus 7.9 months (hazard ratio 0.44). Differentiation syndrome occurred in 14% of ivosidenib patients; febrile neutropenia and infections were less frequent than with azacitidine alone, partly because of faster count recovery. The result established a mutation-directed doublet for this subgroup.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2022
- DOI: 10.1056/NEJMoa2117344
- Authors: Montesinos P, Recher C, Vives S, et al.
- Findings: 146 patients with untreated IDH1-mutated AML unfit for intensive chemotherapy; ivosidenib + azacitidine vs placebo + azacitidine.; Event-free survival hazard ratio 0.33.; Complete remission 47% vs 15%.; Median OS 24.0 vs 7.9 months; hazard ratio 0.44.; Differentiation syndrome 14%; fewer infections and febrile neutropenia than the control arm.
- What it means: AGILE showed that for the roughly 6-10% of AML patients with an IDH1 mutation, a targeted doublet produces survival in the range of two years, an outcome previously unimaginable in unfit patients. Ivosidenib-azacitidine is approved and is one option alongside venetoclax-azacitidine for these patients. Which regimen, or triplet, is best for IDH1-mutated disease has not been settled by a randomised trial.
- Caveats: Small trial that stopped enrolment early; wide confidence intervals.; Enrolled before venetoclax-azacitidine became standard, so the comparator is azacitidine alone.; Restricted to IDH1; IDH2-mutated AML is treated with enasidenib or venetoclax-based regimens.; Differentiation syndrome needs prompt recognition.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa2117344
- ClinicalTrials.gov NCT03173248: https://clinicaltrials.gov/study/NCT03173248

## Connected records

- 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/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Acute myeloid leukaemia in older or unfit patients](https://onco.cc/cancers/aml-older-unfit/), [IDH1- and IDH2-mutated acute myeloid leukaemia](https://onco.cc/cancers/aml-idh/)
- drugs: [Azacitidine](https://onco.cc/drugs/azacitidine/), [Ivosidenib](https://onco.cc/drugs/ivosidenib/), [Venetoclax](https://onco.cc/drugs/venetoclax/)
- companies: [Servier](https://onco.cc/companies/servier/)
- terms: [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/), [Overall survival (OS)](https://onco.cc/terms/os/)
- trials: [AGILE](https://onco.cc/trials/agile/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [Trials enrol too few, too slowly](https://onco.cc/bottlenecks/b-trial-enrolment/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- people: [Courtney D. DiNardo](https://onco.cc/people/courtney-dinardo/)

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