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

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 < 0.001) and non-complex karyotype ( 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.