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Prognostic significance of concurrent gene mutations i n intensively treated patients with IDH-mutated AML: an ALFA study

Matthieu Duchmann 1 Jean-Baptiste Micol 2 Nicolas Duployez 3 Emmanuel Raffoux 4 Xavier Thomas 5 Jean-Pierre Marolleau 6, 7 Thorsten Braun 8 Lionel Ades 4, 9 Sylvain Chantepie 10 Emilie Lemasle 11 Celine Berthon 12 Jean-Valere Malfuson 13 Cecile Pautas 14 Juliette Lambert 15, 16 Nicolas Boissel 4 Karine Celli-Lebras 17 Denis Caillot 18 Pascal Turlure 19 Norbert Vey 20 Arnaud Pigneux 21 Christian Recher 22 Christine Terre 15 Claude Gardin 23 Raphael Itzykson 1 Claude Preudhomme 3 Herve Dombret 4 Stephane De Botton 
Abstract : In patients with isocitrate dehydrogenase (IDH)-mutated acute myeloid leukemia (AML) treated by intensive chemotherapy (IC), prognostic significance of co-occurring genetic alterations and allogeneic hematopoietic stem cell transplantation (HSCT) are of particular interest with the advent of IDH1/2 mutant inhibitors. We retrospectively analyzed 319 patients with newly diagnosed AML (127 with IDH1, 135 with IDH2R140, and 57 with IDH2R172 mutations) treated with IC in 3 Acute Leukemia French Association prospective trials. In each IDH subgroup, we analyzed the prognostic impact of clinical and genetic covariates, and the role of HSCT. In patients with IDH1 mutations, the presence of NPM1 mutations was the only variable predicting improved overall survival (OS) in multivariate analysis (P< .0001). In IDH2R140-mutated AML, normal karyotype (P = .008) and NPM1 mutations (P = .01) predicted better OS. NPM1 mutations were associated with better disease-free survival (DFS; P = .0009), whereas the presence of DNMT3A mutations was associated with shorter DFS (P = .0006). In IDH2R172-mutated AML, platelet count was the only variable retained in the multivariate model for OS (P = .002). Among nonfavorable European LeukemiaNet 2010-eligible patients, 71 (36%) underwent HSCT in first complete remission (CR1) and had longer OS (P = .03) and DFS (P = .02) than nontransplanted patients. Future clinical trials testing frontline IDH inhibitors combined with IC may consider stratification on NPM1 mutational status, the primary prognostic factor in IDH1- or IDH2R140-mutated AML. HSCT improve OS of nonfavorable IDH1/2-mutated AML and should be fully integrated into the treatment strategy.
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Soumis le : jeudi 10 mars 2022 - 16:47:06
Dernière modification le : samedi 3 septembre 2022 - 14:28:27

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Matthieu Duchmann, Jean-Baptiste Micol, Nicolas Duployez, Emmanuel Raffoux, Xavier Thomas, et al.. Prognostic significance of concurrent gene mutations i n intensively treated patients with IDH-mutated AML: an ALFA study. Blood, American Society of Hematology, 2021, 137 (20), pp.2827-2837. ⟨10.1182/blood.2020010165⟩. ⟨hal-03604929⟩



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