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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 treate...

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Hauptverfasser: Middeke, Jan Moritz (VerfasserIn) , Metzeler, Klaus H. (VerfasserIn) , Röllig, Christoph (VerfasserIn) , Krämer, Michael (VerfasserIn) , Eckardt, JanNiklas (VerfasserIn) , Stasik, Sebastian (VerfasserIn) , Greif, Philipp* (VerfasserIn) , Spiekermann, Karsten (VerfasserIn) , RothenbergThurley, Maja (VerfasserIn) , Krug, Utz (VerfasserIn) , Braess, Jan (VerfasserIn) , Krämer, Alwin (VerfasserIn) , Hochhaus, Andreas (VerfasserIn) , Brümmendorf, Tim Henrik (VerfasserIn) , Naumann, Ralph (VerfasserIn) , Steffen, Björn (VerfasserIn) , Einsele, Hermann (VerfasserIn) , Schaich, Markus (VerfasserIn) , Burchert, Andreas (VerfasserIn) , Neubauer, Andreas (VerfasserIn) , Görlich, Dennis (VerfasserIn) , Sauerland, Cristina (VerfasserIn) , SchäferEckart, Kerstin (VerfasserIn) , Schliemann, Christoph (VerfasserIn) , Krause, Stefan W. (VerfasserIn) , Hänel, Mathias (VerfasserIn) , Frickhofen, Norbert (VerfasserIn) , Noppeney, Richard (VerfasserIn) , Kaiser, Ulrich (VerfasserIn) , Kaufmann, Martin (VerfasserIn) , Kunadt, Désirée (VerfasserIn) , Wörmann, Bernhard (VerfasserIn) , Sockel, Katja (VerfasserIn) , Bonin, Malte von (VerfasserIn) , Herold, Tobias (VerfasserIn) , MüllerTidow, Carsten (VerfasserIn) , Platzbecker, Uwe (VerfasserIn) , Berdel, Wolfgang E. (VerfasserIn) , Serve, Hubert (VerfasserIn) , Baldus, Claudia D. (VerfasserIn) , Ehninger, Gerhard (VerfasserIn) , Schetelig, Johannes (VerfasserIn) , Hiddemann, Wolfgang (VerfasserIn) , Bornhäuser, Martin (VerfasserIn) , Stölzel, Friedrich (VerfasserIn) , Thiede, Christian (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: March 8 2022
In: Blood advances
Year: 2022, Jahrgang: 6, Heft: 5, Pages: 13941405
ISSN:24739537
DOI:10.1182/bloodadvances.2021004934
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/bloodadvances.2021004934
Volltext
Verfasserangaben:Jan M. Middeke, Klaus H. Metzeler, Christoph Röllig, Michael Krämer, Jan-Niklas Eckardt, Sebastian Stasik, Philipp A. Greif, Karsten Spiekermann, Maja Rothenberg-Thurley, Utz Krug, Jan Braess, Alwin Krämer, Andreas Hochhaus, Tim H. Brümmendorf, Ralph Naumann, Björn Steffen, Hermann Einsele, Markus Schaich, Andreas Burchert, Andreas Neubauer, Dennis Görlich, Cristina Sauerland, Kerstin Schäfer-Eckart, Christoph Schliemann, Stefan W. Krause, Mathias Hänel, Norbert Frickhofen, Richard Noppeney, Ulrich Kaiser, Martin Kaufmann, Desiree Kunadt, Bernhard Wörmann, Katja Sockel, Malte von Bonin, Tobias Herold, Carsten Müller-Tidow, Uwe Platzbecker, Wolfgang E. Berdel, Hubert Serve, Claudia D. Baldus, Gerhard Ehninger, Johannes Schetelig, Wolfgang Hiddemann, Martin Bornhäuser, Friedrich Stölzel, and Christian Thiede
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 27.07.2022
Beschreibung:Online Resource
ISSN:24739537
DOI:10.1182/bloodadvances.2021004934

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