• Medientyp: E-Artikel
  • Titel: 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
  • Beteiligte: Bouvier, Anne; Hamel, Jean‐François; Delaunay, Jacques; Delabesse, Eric; Dumas, Pierre‐Yves; Ledoux, Marie‐Pierre; Peterlin, Pierre; Luquet, Isabelle; Roth Guepin, Gabrielle; Bulabois, Claude Eric; Gallego Hernanz, Maria Pilar; Guillerm, Gaëlle; Guieze, Romain; Hicheri, Yosr; Simand, Célestine; Himberlin, Chantal; Hunault‐Berger, Mathilde; Bernard, Marc; Jourdan, Eric; Caillot, Denis; Dorvaux, Véronique; Tavernier, Emmanuelle; Daguindau, Etienne; Banos, Anne; [...]
  • Erschienen: Wiley, 2021
  • Erschienen in: European Journal of Haematology
  • Umfang: 111-121
  • Sprache: Englisch
  • DOI: 10.1111/ejh.13626
  • ISSN: 0902-4441; 1600-0609
  • Schlagwörter: Hematology ; General Medicine
  • Zusammenfassung: <jats:title>Abstract</jats:title><jats:p>In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m<jats:sup>2</jats:sup> of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with <jats:italic>de novo</jats:italic> 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 (&lt;60 years) ineligible for allogeneic stem‐cell transplantation. (<jats:italic>P</jats:italic> = .086; <jats:italic>P</jats:italic> = .149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of seven genes (<jats:italic>NPM1</jats:italic>, <jats:italic>FLT3</jats:italic>‐ITD, <jats:italic>CEBPA</jats:italic>, <jats:italic>DNMT3A</jats:italic>, <jats:italic>IDH1</jats:italic>, <jats:italic>IDH2</jats:italic>, and <jats:italic>ASXL1</jats:italic>), six clusters of patients with significant different outcome were identified. Five clusters were based on <jats:italic>FLT3</jats:italic>‐ITD, <jats:italic>NPM1</jats:italic>, and <jats:italic>CEBPA</jats:italic> mutations as well as epigenetic modifiers (<jats:italic>DNMT3A</jats:italic>, <jats:italic>IDH1/2</jats:italic>, <jats:italic>ASXL1</jats:italic>), whereas the last cluster, representing 25% of patients, had no mutation and intermediate risk. One cluster isolated <jats:italic>FLT3</jats:italic>‐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 &lt;60 years, this study provides a molecular classification that distinguishes six AML clusters influencing prognosis in younger AML patients with intermediate‐risk cytogenetic.</jats:p>
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m<jats:sup>2</jats:sup> of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with <jats:italic>de novo</jats:italic> 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 (&lt;60 years) ineligible for allogeneic stem‐cell transplantation. (<jats:italic>P</jats:italic> = .086; <jats:italic>P</jats:italic> = .149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of seven genes (<jats:italic>NPM1</jats:italic>, <jats:italic>FLT3</jats:italic>‐ITD, <jats:italic>CEBPA</jats:italic>, <jats:italic>DNMT3A</jats:italic>, <jats:italic>IDH1</jats:italic>, <jats:italic>IDH2</jats:italic>, and <jats:italic>ASXL1</jats:italic>), six clusters of patients with significant different outcome were identified. Five clusters were based on <jats:italic>FLT3</jats:italic>‐ITD, <jats:italic>NPM1</jats:italic>, and <jats:italic>CEBPA</jats:italic> mutations as well as epigenetic modifiers (<jats:italic>DNMT3A</jats:italic>, <jats:italic>IDH1/2</jats:italic>, <jats:italic>ASXL1</jats:italic>), whereas the last cluster, representing 25% of patients, had no mutation and intermediate risk. One cluster isolated <jats:italic>FLT3</jats:italic>‐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 &lt;60 years, this study provides a molecular classification that distinguishes six AML clusters influencing prognosis in younger AML patients with intermediate‐risk cytogenetic.</jats:p>
  • Anmerkungen: