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.

In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m2 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.