Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. Issue 8 (August 2015)

• Record Type: Journal Article
• Authors: DiNardo, Courtney D.; Ravandi, Farhad; Agresta, Sam; Konopleva, Marina; Takahashi, Koichi; Kadia, Tapan; Routbort, Mark; Patel, Keyur P.; Mark Brandt; Pierce, Sherry; Garcia‐Manero, Guillermo; Cortes, Jorge; Kantarjian, Hagop
• Is Part Of: American journal of hematology. Volume 90:Issue 8(2015:Aug.)
• Page Start: 732
• Page End: 736
• Publication Date: 2015-08
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.24072
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The pathophysiology of <italic>IDH</italic> mutations in tumorigenesis is increasingly described, yet the prognostic significance of <italic>IDH1</italic> and <italic>IDH2</italic> mutations in AML remains controversial. The primary objective of this study was to define the natural history and prognosis of patients with AML and <italic>IDH1</italic> or <italic>IDH2</italic> 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 <italic>IDH1</italic> or <italic>IDH2</italic> mutations. Median age was 62 years (range 18–92). There were 59 <italic>IDH1</italic>‐R132, 83 <italic>IDH2</italic>‐R140, and 23 <italic>IDH2</italic>‐R172 mutations. Clinicopathologic characteristics associated with <italic>IDH</italic>‐mutations included older age, less frequent therapy‐related status, and increased incidence of intermediate‐risk cytogenetics, <italic>FLT3‐ITD</italic> mutations, and <italic>NPM1</italic> 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 <italic>IDH</italic> mutation status. Similarly, overall survival (OS) was not dependent on <italic>IDH</italic> 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 <italic>IDH</italic>‐mutations in both the front‐line and salvage AML treatment settings, and confirms that response rate and OS for both <italic>IDH</italic>‐mutated and <italic>IDH</italic> wild‐type AML patients is comparable. This provides contemporary data to be used for comparison with results of novel investigational (e.g., selective <italic>IDH</italic> inhibitor) strategies. Am. J. Hematol. 90:732–736, 2015. © 2015 Wiley Periodicals, Inc.</p> </abstract>