Differential impact of IDH1/2 mutational subclasses on outcome in adult AML: results from a large multicenter study

  • Mutations of the isocitrate dehydrogenase-1 (IDH1) and IDH2 genes are among the most frequent alterations in acute myeloid leukemia (AML) and can be found in ∼20% of patients at diagnosis. Among 4930 patients (median age, 56 years; interquartile range, 45-66) with newly diagnosed, intensively treated AML, we identified IDH1 mutations in 423 (8.6%) and IDH2 mutations in 575 (11.7%). Overall, there were no differences in response rates or survival for patients with mutations in IDH1 or IDH2 compared with patients without mutated IDH1/2. However, distinct clinical and comutational phenotypes of the most common subtypes of IDH1/2 mutations could be associated with differences in outcome. IDH1-R132C was associated with increased age, lower white blood cell (WBC) count, less frequent comutation of NPM1 and FLT3 internal tandem mutation (ITD) as well as with lower rate of complete remission and a trend toward reduced overall survival (OS) compared with other IDH1 mutation variants and wild-type (WT) IDH1/2. In our analysis, IDH2-R172K was associated with significantly lower WBC count, more karyotype abnormalities, and less frequent comutations of NPM1 and/or FLT3-ITD. Among patients within the European LeukemiaNet 2017 intermediate- and adverse-risk groups, relapse-free survival and OS were significantly better for those with IDH2-R172K compared with WT IDH, providing evidence that AML with IDH2-R172K could be a distinct entity with a specific comutation pattern and favorable outcome. In summary, the presented data from a large cohort of patients with IDH1/2 mutated AML indicate novel and clinically relevant findings for the most common IDH mutation subtypes.

Download full text files

Export metadata

Author:Jan Moritz MiddekeORCiDGND, Klaus Hans MetzelerORCiDGND, Christoph RölligORCiDGND, Michael KrämerORCiD, Jan-Niklas EckardtORCiDGND, Sebastian StasikORCiDGND, Philipp GreifORCiDGND, Karsten SpiekermannORCiD, Maja Rothenberg-Thurley, Utz KrugGND, Jan BraessGND, Alwin KrämerORCiDGND, Andreas HochhausORCiDGND, Tim Henrik BrümmendorfORCiDGND, Ralph NaumannGND, Björn SteffenGND, Hermann EinseleORCiDGND, Markus SchaichGND, Andreas BurchertGND, Andreas NeubauerORCiDGND, Dennis GörlichORCiDGND, Cristina SauerlandORCiD, Kerstin Schäfer-Eckart, Christoph SchliemannGND, Stefan W. KrauseORCiDGND, Mathias HänelGND, Norbert FrickhofenORCiDGND, Richard Noppeney, Ulrich Kaiser, Martin Kaufmann, Désirée KunadtORCiDGND, Bernhard WörmannORCiDGND, Katja SockelGND, von Malte BoninORCiDGND, Tobias HeroldORCiDGND, Carsten Müller-TidowORCiDGND, Uwe PlatzbeckerORCiDGND, Wolfgang E. BerdelORCiDGND, Hubert ServeORCiDGND, Claudia BaldusORCiDGND, Gerhard EhningerGND, Johannes ScheteligORCiDGND, Wolfgang HiddemannGND, Martin BornhäuserORCiDGND, Friedrich StölzelORCiDGND, Christian ThiedeORCiDGND
Parent Title (English):Blood advances
Publisher:American Society of Hematology
Place of publication:Washington, DC
Document Type:Article
Date of Publication (online):2022/02/25
Date of first Publication:2022/02/25
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/04/03
Tag:Clinical Trials and Observations; Myeloid Neoplasia
Page Number:12
First Page:1394
Last Page:1405
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International