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. 2022 Jun 18;14(12):3012.
doi: 10.3390/cancers14123012.

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

Monica Messina  1 , Alfonso Piciocchi  1 , Tiziana Ottone  2   3 , Stefania Paolini  4 , Cristina Papayannidis  4 , Federica Lessi  5 , Nicola Stefano Fracchiolla  6 , Fabio Forghieri  7 , Anna Candoni  8 , Andrea Mengarelli  9 , Maria Paola Martelli  10 , Adriano Venditti  2 , Angelo Michele Carella  11 , Francesco Albano  12 , Valentina Mancini  13 , Bernardi Massimo  14 , Valentina Arena  1 , Valeria Sargentini  1 , Mariarita Sciumè  6 , Domenico Pastore  15 , Elisabetta Todisco  16 , Giovanni Roti  17 , Sergio Siragusa  18 , Marco Ladetto  19 , Stefano Pravato  5 , Eleonora De Bellis  20 , Giorgia Simonetti  21 , Giovanni Marconi  22 , Claudio Cerchione  22 , Paola Fazi  1 , Marco Vignetti  1 , Sergio Amadori  2 , Giovanni Martinelli  21 , Maria Teresa Voso  2   3
Affiliations

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

Monica Messina et al. Cancers (Basel). .

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.

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Conflict of interest statement

M.V.: Amgen; Novartis, Mattioli srl; IQVIA; Dephaforum S.r.l.; M.L.: AbbVie, Acerta, Amgen, ADC Therapeutics, Astra Zeneca, BeiGene Celgene, GSKI, Gentili, Gilead/Kite, Novartis, Incyte J and J, Jazz, Regeneron, Roche, Sandoz, Takeda. Non-financial interests: PI or strategic investigator in studies supported by: Celgene, J&J, BeiGene, ADC Therapeutics; GMartinelli: Abbvie; Incyte; Pfizer; Celgene/BMS; Amgen, Roche; GlaxoSmithKline; Astellas; Daiichi Sankyo; Takeda; Janssen; Servier. Research support from: Pfizer, AbbVie, AstraZeneca, Daiichi Sankyo, Takeda, and Ariad/Incyte. GMarconi: Menarini/stemline, Pfizer, Servier, and Astellas and research support from Pfizer, AbbVie, and AstraZeneca. The other authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
(A) Incidence of IDH1/2 mutations at AML diagnosis; distribution of IDH1 (B) and IDH2 (C) mutation subtypes.
Figure 2
Figure 2
(A) OS by IDH1/2 mutations; (B) EFS by IDH1/2 mutations; (C) OS by the most frequent IDH1/2 mutations; (D) EFS by the most frequent IDH1/2 mutations.
See this image and copyright information in PMC

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