Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML

Courtney D. Dinardo, Farhad Ravandi, Sam Agresta, Marina Konopleva, Koichi Takahashi, Tapan Kadia, Mark Routbort, Keyur P. Patel, Brandt Mark Brandt, Sherry Pierce, Guillermo Garcia-Manero, Jorge Cortes, Hagop Kantarjian

Research output: Contribution to journalArticle

Abstract

The pathophysiology of IDH mutations in tumorigenesis is increasingly described, yet the prognostic significance of IDH1 and IDH2 mutations in AML remains controversial. The primary objective of this study was to define the natural history and prognosis of patients with AML and IDH1 or IDH2 mutations and provide historical survival expectations. A total of 826 patients treated from 2010 to 2014 at a single institution were evaluated, including 167 patients (20%) with AML and IDH1 or IDH2 mutations. Median age was 62 years (range 18-92). There were 59 IDH1-R132, 83 IDH2-R140, and 23 IDH2-R172 mutations. Clinicopathologic characteristics associated with IDH-mutations included older age, less frequent therapy-related status, and increased incidence of intermediate-risk cytogenetics, FLT3-ITD mutations, and NPM1 mutations. Remission rates (CR/CRi) by AML treatment status were: induction, 68%; Salvage-1 (S1), 42%; and Salvage-2 and beyond (S2+), 27%. No difference in response was identified by IDH mutation status. Similarly, overall survival (OS) was not dependent on IDH status within any cohort. The median OS was 15.4 months in induction, 8.7 months in S1, and 4.8 months in S2+. This analysis defines the clinical outcome associated with IDH-mutations in both the front-line and salvage AML treatment settings, and confirms that response rate and OS for both IDH-mutated and IDH wild-type AML patients is comparable. This provides contemporary data to be used for comparison with results of novel investigational (e.g., selective IDH inhibitor) strategies.

Original languageEnglish (US)
Pages (from-to)732-736
Number of pages5
JournalAmerican Journal of Hematology
Volume90
Issue number8
DOIs
StatePublished - Aug 1 2015

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Mutation
Survival
Salvage Therapy
Natural History
Cytogenetics
Carcinogenesis
Survival Rate
Incidence
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

Dinardo, C. D., Ravandi, F., Agresta, S., Konopleva, M., Takahashi, K., Kadia, T., ... Kantarjian, H. (2015). Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. American Journal of Hematology, 90(8), 732-736. https://doi.org/10.1002/ajh.24072

Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. / Dinardo, Courtney D.; Ravandi, Farhad; Agresta, Sam; Konopleva, Marina; Takahashi, Koichi; Kadia, Tapan; Routbort, Mark; Patel, Keyur P.; Mark Brandt, Brandt; Pierce, Sherry; Garcia-Manero, Guillermo; Cortes, Jorge; Kantarjian, Hagop.

In: American Journal of Hematology, Vol. 90, No. 8, 01.08.2015, p. 732-736.

Research output: Contribution to journalArticle

Dinardo, CD, Ravandi, F, Agresta, S, Konopleva, M, Takahashi, K, Kadia, T, Routbort, M, Patel, KP, Mark Brandt, B, Pierce, S, Garcia-Manero, G, Cortes, J & Kantarjian, H 2015, 'Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML', American Journal of Hematology, vol. 90, no. 8, pp. 732-736. https://doi.org/10.1002/ajh.24072
Dinardo CD, Ravandi F, Agresta S, Konopleva M, Takahashi K, Kadia T et al. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. American Journal of Hematology. 2015 Aug 1;90(8):732-736. https://doi.org/10.1002/ajh.24072
Dinardo, Courtney D. ; Ravandi, Farhad ; Agresta, Sam ; Konopleva, Marina ; Takahashi, Koichi ; Kadia, Tapan ; Routbort, Mark ; Patel, Keyur P. ; Mark Brandt, Brandt ; Pierce, Sherry ; Garcia-Manero, Guillermo ; Cortes, Jorge ; Kantarjian, Hagop. / Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. In: American Journal of Hematology. 2015 ; Vol. 90, No. 8. pp. 732-736.
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