{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:45:47Z","timestamp":1790019947745,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005189","name":"Leukemia and Lymphoma Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001368","name":"V Foundation for Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001368","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2022,11]]},"abstract":"Abstract<\/jats:title>Isocitrate dehydrogenase 1 or 2 (IDH1<\/jats:italic> or IDH2<\/jats:italic>) mutations occur frequently in newly diagnosed (ND) acute myeloid leukemia (AML) often with co\u2010occurring NPM1<\/jats:italic> mutations, which may influence treatment outcomes. Detailed analysis of IDH<\/jats:italic>\u2010mutated AML treated with venetoclax and influence of co\u2010occurring NPM1<\/jats:italic> mutations remains unclear. This retrospective single\u2010center cohort study evaluated clinical and molecular demographics,response and survival, and impact of co\u2010occurring NPM1<\/jats:italic> mutations in patients with IDH1<\/jats:italic> or IDH2<\/jats:italic>\u2010mutated AML. 556 patients with IDH1<\/jats:italic>, IDH2<\/jats:italic>, and\/or NPM1<\/jats:italic> mutated AML were included. Patients with IDH1<\/jats:italic>mut<\/jats:italic><\/jats:sup> AML (N<\/jats:italic>\u00a0=\u2009119) were more likely to have older age, sAML, ELN\u2010adverse risk disease, and adverse\u2010risk cytogenetics compared to those with IDH2<\/jats:italic>mut<\/jats:italic><\/jats:sup> (N<\/jats:italic>\u00a0=\u2009229) or IDH<\/jats:italic>wt<\/jats:italic><\/jats:sup>\/NPM1<\/jats:italic>mut<\/jats:italic><\/jats:sup> AML (N<\/jats:italic>\u00a0=\u2009208). In multivariate analysis, patients with IDH2<\/jats:italic>mut<\/jats:italic><\/jats:sup> (HR 0.61 [95%CI: 0.43\u20130.88], p<\/jats:italic> value: .007) or IDH<\/jats:italic>wt<\/jats:italic><\/jats:sup>\/NPM1<\/jats:italic>mut<\/jats:italic><\/jats:sup> (HR 0.65 [95% CI: 0.45\u20130.94], p<\/jats:italic> value: .024) AML had a decreased risk of death versus IDH1<\/jats:italic>mut<\/jats:sup> AML. Venetoclax\u2010based lower\u2010intensity regimens partially abrogated the detrimental effect of IDH1<\/jats:italic>mut<\/jats:italic><\/jats:sup> with similar OS observed between IDH1<\/jats:italic>mut<\/jats:italic><\/jats:sup>\/NPM1<\/jats:italic>wt<\/jats:italic><\/jats:sup>, IDH2<\/jats:italic>mut<\/jats:italic><\/jats:sup>\/NPM1<\/jats:italic>wt<\/jats:italic><\/jats:sup>, and IDH<\/jats:italic>wt<\/jats:italic><\/jats:sup>\/NPM1<\/jats:italic>mut<\/jats:italic><\/jats:sup> AML. With regards to the influence of IDH<\/jats:italic>mut<\/jats:italic><\/jats:sup>\/NPM1<\/jats:italic>mut<\/jats:italic><\/jats:sup> cases, IC improved survival in IDH2<\/jats:italic>mut<\/jats:italic><\/jats:sup>\/NPM1<\/jats:italic>mut<\/jats:italic><\/jats:sup> versus IDH2<\/jats:italic>mut<\/jats:italic><\/jats:sup>\/NPM1<\/jats:italic>wt<\/jats:italic><\/jats:sup> AML (HR: 0.54 [95% CI: 0.2644\u20131.082], p<\/jats:italic> value: .077), while venetoclax\u2010based therapy improved survival in IDH1<\/jats:italic>mut<\/jats:italic><\/jats:sup>\/NPM1<\/jats:italic>mut<\/jats:italic><\/jats:sup> versus IDH1<\/jats:italic>mut<\/jats:italic><\/jats:sup>\/NPM1<\/jats:italic>wt<\/jats:italic><\/jats:sup> AML (HR: 0.094 [95% CI: 0.01\u20130.74], p<\/jats:italic> value: .0056). Differing outcomes were observed in IDH1<\/jats:italic>mut<\/jats:italic><\/jats:sup> versus IDH2<\/jats:italic>mut<\/jats:sup> or NPM1<\/jats:italic>mut<\/jats:italic><\/jats:sup> AML which were influenced by co\u2010occurring NPM1<\/jats:italic> mutations and partially abrogated with venetoclax\u2010based therapy. Given the differing biology and survival in IDH1<\/jats:italic>mut<\/jats:italic><\/jats:sup> AML, investigations incorporating molecularly targeted therapies such as IDH inhibitors remain warranted in this subgroup.<\/jats:p>","DOI":"10.1002\/ajh.26694","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T17:53:50Z","timestamp":1661190830000},"page":"1443-1452","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Contemporary outcomes in IDH<\/i><\/scp>\u2010mutated acute myeloid leukemia: The impact of co\u2010occurring NPM1<\/i><\/scp> mutations and venetoclax\u2010based treatment"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-0624","authenticated-orcid":false,"given":"Curtis A.","family":"Lachowiez","sequence":"first","affiliation":[{"name":"Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston Texas 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