Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial
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Eric Delabesse
- Fonction : Auteur
- PersonId : 769021
- ORCID : 0000-0002-0928-0753
Pierre-Yves Dumas
- Fonction : Auteur
- PersonId : 783354
- ORCID : 0000-0003-0119-3548
Marie-Pierre Ledoux
- Fonction : Auteur
- PersonId : 786146
- ORCID : 0000-0002-3261-3616
Pierre Peterlin
- Fonction : Auteur
- PersonId : 776625
- ORCID : 0000-0001-5463-6686
Mathilde Hunault-Berger
- Fonction : Auteur
- PersonId : 752203
- IdHAL : mathilde-hunault-berger
- ORCID : 0000-0001-7777-5216
Jean-Pierre Marolleau
- Fonction : Auteur
- PersonId : 887235
- IdRef : 06981676X
Catherine Humbrecht
- Fonction : Auteur
Odile Blanchet
- Fonction : Auteur
- PersonId : 749083
- IdHAL : odile-blanchet
- ORCID : 0000-0002-8275-8741
Norbert Vey
- Fonction : Auteur
- PersonId : 762211
- ORCID : 0000-0001-7027-040X
Christian Recher
- Fonction : Auteur
- PersonId : 758643
- ORCID : 0000-0002-3332-4525
Résumé
In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m(2) 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 = .086; P = .149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of seven genes (NPM1, FLT3-ITD, CEBPA, DNMT3A, IDH1, IDH2, and ASXL1), six 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 no impact in these molecular clusters. Although not conclusive for GO impact in AML patients <60 years, this study provides a molecular classification that distinguishes six AML clusters influencing prognosis in younger AML patients with intermediate-risk cytogenetic.