Fiche publication
Date publication
février 2021
Journal
Blood
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CAILLOT Denis
Tous les auteurs :
Duchmann M, Micol JB, Duployez N, Raffoux E, Thomas X, Marolleau JP, Braun T, Adès L, Chantepie SP, Lemasle E, Berthon C, Malfuson JV, Pautas C, Lambert J, Boissel N, Celli-Lebras K, Caillot D, Turlure P, Vey N, Pigneux A, Récher C, Terré C, Gardin CJ, Itzykson RA, Preudhomme C, Dombret H, de Botton S
Lien Pubmed
Résumé
IDH inhibitors are effective in AML, and trials evaluating frontline combinations with intensive chemotherapy (IC) are ongoing. Data on the prognostic significance of co-occurring genetic alterations and allogeneic hematopoietic stem cell transplantation (HSCT) are conflicting in each IDH-mutated subgroup treated by IC, while this information is important for trial design and results interpretation. We retrospectively analyzed 127 IDH1, 135 IDH2R140 and 57 IDH2R172 newly diagnosed AML patients treated with IC in three Acute Leukemia French Association (ALFA) prospective trials. We addressed in each IDH subgroup the prognostic impact of clinical and genetic covariates, and the role of HSCT in eligible patients. In IDH1 patients, presence of NPM1 mutations was the only variable predicting improved OS in multivariate analysis (p < 0.0001). In IDH2R140, normal karyotype (p= 0.008) and NPM1 mutations (p = 0.01) predicted better OS. NPM1 mutations were associated with better DFS (p = 0.0009) whereas presence of DNMT3A mutations was associated with shorter DFS (p = 0.0006). In IDH2R172, platelet count was the only variable retained in the multivariate model for OS (p = 0.002). Among non-favorable ELN-2010 eligible patients, 71 (36%) achieved an HSCT in first complete remission (CR1) and had longer OS (p = 0.03) and DFS (p = 0.02) than not-transplanted patients. Future clinical trial testing frontline IDH inhibitors combined with IC may consider stratification on NPM1 mutational status, the main prognostic factor in IDH1 and IDH2R140 mutated AML. HSCT improve OS of non-favorable IDH1/2-mutated AML and should be fully integrated in the treatment strategy.
Référence
Blood. 2021 Feb 24;:
