Cancers (Jun 2022)

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol

  • Monica Messina,
  • Alfonso Piciocchi,
  • Tiziana Ottone,
  • Stefania Paolini,
  • Cristina Papayannidis,
  • Federica Lessi,
  • Nicola Stefano Fracchiolla,
  • Fabio Forghieri,
  • Anna Candoni,
  • Andrea Mengarelli,
  • Maria Paola Martelli,
  • Adriano Venditti,
  • Angelo Michele Carella,
  • Francesco Albano,
  • Valentina Mancini,
  • Bernardi Massimo,
  • Valentina Arena,
  • Valeria Sargentini,
  • Mariarita Sciumè,
  • Domenico Pastore,
  • Elisabetta Todisco,
  • Giovanni Roti,
  • Sergio Siragusa,
  • Marco Ladetto,
  • Stefano Pravato,
  • Eleonora De Bellis,
  • Giorgia Simonetti,
  • Giovanni Marconi,
  • Claudio Cerchione,
  • Paola Fazi,
  • Marco Vignetti,
  • Sergio Amadori,
  • Giovanni Martinelli,
  • Maria Teresa Voso

DOI
https://doi.org/10.3390/cancers14123012
Journal volume & issue
Vol. 14, no. 12
p. 3012

Abstract

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IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19–86). Of these, 38 (14%) harbored IDH1 and 51 (18%) IDH2 mutations. IDH1/2 mutations were significantly associated with WHO PS >2 (p p = 0.021) when compared to IDH1/2-WT. Furthermore, patients with IDH1 mutations were more frequently NPM1-mutated (p = 0.007) and had a higher platelet count (p = 0.036). At relapse, IDH1/2 mutations were detected in 6 (25%) patients. As per the outcome, 60.5% of IDH1/2-mutated patients achieved complete remission; overall survival and event-free survival at 2 years were 44.5% and 36.1%, respectively: these rates were similar to IDH1/2-WT. In IDH1/2-mutated patients, high WBC proved to be an independent prognostic factor for survival. In conclusion, the GIMEMA AML1516 confirms that IDH1/2 mutations are frequently detected at diagnosis and underlines the importance of recognizing IDH1/2-mutated cases up-front to offer the most appropriate therapeutic strategy, given the availability of IDH1/2 inhibitors.

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