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:10.3390/cancers14123012

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 PastoreElisabetta 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

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

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.

Lingua originale	Inglese
Numero di articolo	3012
Rivista	Cancers
Volume	14
Numero di pubblicazione	12
DOI	https://doi.org/10.3390/cancers14123012
Stato di pubblicazione	Pubblicato - 1 giu 2022
Pubblicato esternamente	Sì

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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., Sciumè, M., ... Voso, M. T. (2022). Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol. Cancers, 14(12), Articolo 3012. https://doi.org/10.3390/cancers14123012

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

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.",

keywords = "AML, DH1, IDH2, prevalence, prognosis",

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

note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = jun,

day = "1",

doi = "10.3390/cancers14123012",

language = "English",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "12",

}

Messina, M, Piciocchi, A, Ottone, T, Paolini, S, Papayannidis, C, Lessi, F, Fracchiolla, NS, Forghieri, F, Candoni, A, Mengarelli, A, Martelli, MP, Venditti, A, Carella, AM, Albano, F, Mancini, V, Massimo, B, Arena, V, Sargentini, V, Sciumè, 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, MT 2022, 'Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol', Cancers, vol. 14, n. 12, 3012. https://doi.org/10.3390/cancers14123012

TY - JOUR

T1 - Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia

T2 - Results of the GIMEMA AML1516 Protocol

AU - Messina, Monica

AU - Piciocchi, Alfonso

AU - Ottone, Tiziana

AU - Paolini, Stefania

AU - Papayannidis, Cristina

AU - Lessi, Federica

AU - Fracchiolla, Nicola Stefano

AU - Forghieri, Fabio

AU - Candoni, Anna

AU - Mengarelli, Andrea

AU - Martelli, Maria Paola

AU - Venditti, Adriano

AU - Carella, Angelo Michele

AU - Albano, Francesco

AU - Mancini, Valentina

AU - Massimo, Bernardi

AU - Arena, Valentina

AU - Sargentini, Valeria

AU - Sciumè, Mariarita

AU - Pastore, Domenico

AU - Todisco, Elisabetta

AU - Roti, Giovanni

AU - Siragusa, Sergio

AU - Ladetto, Marco

AU - Pravato, Stefano

AU - De Bellis, Eleonora

AU - Simonetti, Giorgia

AU - Marconi, Giovanni

AU - Cerchione, Claudio

AU - Fazi, Paola

AU - Vignetti, Marco

AU - Amadori, Sergio

AU - Martinelli, Giovanni

AU - Voso, Maria Teresa

PY - 2022/6/1

Y1 - 2022/6/1

N2 - 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.

AB - 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.

KW - AML

KW - DH1

KW - IDH2

KW - prevalence

KW - prognosis

UR - https://www.scopus.com/pages/publications/85132287962

U2 - 10.3390/cancers14123012

DO - 10.3390/cancers14123012

M3 - Article

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 12

M1 - 3012

ER -

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

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