{"entity":{"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","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2117344"},{"label":"ClinicalTrials.gov NCT03173248","url":"https://clinicaltrials.gov/study/NCT03173248"}],"tags":[],"related":["paper-viale-a-venetoclax-azacitidine-nejm-2020"],"cancers":["aml"],"sections":[],"technologies":[],"targets":[],"drugs":["ivosidenib","azacitidine","venetoclax"],"companies":["servier"],"institutions":[],"pathways":[],"terms":["efs","os"],"trials":["agile"],"people":[],"bottlenecks":["b-rare-cancers","b-trial-enrolment"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2117344","authors":"Montesinos P, Recher C, Vives S, et al.","paperType":"rct","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."],"whatItMeans":"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."],"changedPractice":true,"participants":146},"route":"/key-papers/paper-agile-ivosidenib-azacitidine-nejm-2022/","neighbours":{"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/"}],"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-idh","kind":"cancer","name":"IDH1- and IDH2-mutated acute myeloid leukaemia","route":"/cancers/aml-idh/"}],"drug":[{"id":"azacitidine","kind":"drug","name":"Azacitidine","route":"/drugs/azacitidine/"},{"id":"ivosidenib","kind":"drug","name":"Ivosidenib","route":"/drugs/ivosidenib/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"}],"company":[{"id":"servier","kind":"company","name":"Servier","route":"/companies/servier/"}],"term":[{"id":"efs","kind":"term","name":"Event-free / disease-free survival (EFS, DFS, iDFS, RFS)","route":"/terms/efs/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"}],"trial":[{"id":"agile","kind":"trial","name":"AGILE","route":"/trials/agile/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"},{"id":"b-trial-enrolment","kind":"bottleneck","name":"Trials enrol too few, too slowly","route":"/bottlenecks/b-trial-enrolment/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"person":[{"id":"courtney-dinardo","kind":"person","name":"Courtney D. DiNardo","route":"/people/courtney-dinardo/"}]}}