Molecular classification and prognosis in younger adults with acute myeloid leukemia patients and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: final results of the GOELAMS/FILO AML 2006-IR trial.

Fiche publication

Date publication

mars 2021

Journal

European journal of haematology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr CAILLOT Denis , Dr CORNILLET-LEFEBVRE Pascale , Dr DAGUINDAU Etienne , Dr OJEDA-URIBE Mario , Dr DORVAUX Véronique

Tous les auteurs :
Bouvier A, Hamel JF, Delaunay J, Delabesse E, Dumas PY, Ledoux MP, Peterlin P, Luquet I, Guepin GR, Bulabois CE, Hernanz MPG, Guillerm G, Guieze R, Hicheri Y, Simand C, Himberlin C, Hunault-Berger M, Bernard M, Jourdan E, Caillot D, Dorvaux V, Tavernier E, Daguindau E, Banos A, Ojeda-Uribe M, Gyan E, Magda A, Marolleau JP, Turlure P, Bouscary D, Humbrecht C, Zerazhi H, Christine Béné M, Pigneux A, Carre M, Ifrah N, Blanchet O, Vey N, Récher C, Cornillet-Lefèbvre P,

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/33765335

Résumé

In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (<60 years) ineligible for allogeneic stem-cell transplantation. (p=0.086; p=0.149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of 7 genes (NPM1, FLT3-ITD, CEBPA, DNMT3A, IDH1, IDH2, and ASXL1), 6 clusters of patients with significant different outcome were identified. Five clusters were based on FLT3-ITD, NPM1 and CEBPA mutations as well as epigenetic modifiers (DNMT3A, IDH1/2, ASXL1) whereas the last cluster, representing 25% of patients, had no mutation and intermediate risk. One cluster isolated FLT3-ITD mutations with higher allelic ratio and a very poor outcome. The addition of GO had not impact in these molecular clusters. Although not conclusive for GO impact in AML patients <60y, this study provides a molecular classification that distinguishes 6 AML clusters influencing prognosis in younger AML patients with intermediate-risk cytogenetic.