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.

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol / Messina, M.; Piciocchi, A.; Ottone, T.; Paolini, S.; Papayannidis, C.; Lessi, F.; Fracchiolla, N. S.; Forghieri, F.; Candoni, A.; Mengarelli, A.; Martelli, M. P.; Venditti, A.; Carella, A. M.; Albano, F.; Mancini, V.; Massimo, B.; Arena, V.; Sargentini, V.; Sciume, M.; Pastore, D.; Todisco, E.; Roti, G.; Siragusa, S.; Ladetto, M.; Pravato, S.; De Bellis, E.; Simonetti, G.; Marconi, G.; Cerchione, C.; Fazi, P.; Vignetti, M.; Amadori, S.; Martinelli, G.; Voso, M. T.. - In: CANCERS. - ISSN 2072-6694. - 14:12(2022), pp. 3012-3020. [10.3390/cancers14123012]

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

Candoni A.;
2022

Abstract

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.
2022
14
12
3012
3020
Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol / Messina, M.; Piciocchi, A.; Ottone, T.; Paolini, S.; Papayannidis, C.; Lessi, F.; Fracchiolla, N. S.; Forghieri, F.; Candoni, A.; Mengarelli, A.; Martelli, M. P.; Venditti, A.; Carella, A. M.; Albano, F.; Mancini, V.; Massimo, B.; Arena, V.; Sargentini, V.; Sciume, M.; Pastore, D.; Todisco, E.; Roti, G.; Siragusa, S.; Ladetto, M.; Pravato, S.; De Bellis, E.; Simonetti, G.; Marconi, G.; Cerchione, C.; Fazi, P.; Vignetti, M.; Amadori, S.; Martinelli, G.; Voso, M. T.. - In: CANCERS. - ISSN 2072-6694. - 14:12(2022), pp. 3012-3020. [10.3390/cancers14123012]
Messina, M.; Piciocchi, A.; Ottone, T.; Paolini, S.; Papayannidis, C.; Lessi, F.; Fracchiolla, N. S.; Forghieri, F.; Candoni, A.; Mengarelli, A.; Martelli, M. P.; Venditti, A.; Carella, A. M.; Albano, F.; Mancini, V.; Massimo, B.; Arena, V.; Sargentini, V.; Sciume, M.; Pastore, D.; Todisco, E.; Roti, G.; Siragusa, S.; Ladetto, M.; Pravato, S.; De Bellis, E.; Simonetti, G.; Marconi, G.; Cerchione, C.; Fazi, P.; Vignetti, M.; Amadori, S.; Martinelli, G.; Voso, M. T.
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