All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia

• Verfasst von: Schlenk, Richard Friedrich [VerfasserIn]
• Verfasst von: Benner, Axel [VerfasserIn]
• Titel: All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia
• Titelzusatz: results of the randomized AMLSG 07-04 study
• Verf.angabe: Richard F. Schlenk, Michael Lübbert, Axel Benner, Alexander Lamparter, Jürgen Krauter, Wolfgang Herr, Hans Martin, Helmut R. Salih, Andrea Kündgen, Heinz-A. Horst, Peter Brossart, Katharina Götze, David Nachbaur, Mohammed Wattad, Claus-Henning Köhne, Walter Fiedler, Martin Bentz, Gerald Wulf, Gerhard Held, Bernd Hertenstein, Hans Salwender, Verena I. Gaidzik, Brigitte Schlegelberger, Daniela Weber, Konstanze Döhner, Arnold Ganser, Hartmut Döhner, for the German-Austrian Acute Myeloid Leukemia Study Group
• E-Jahr: 2016
• Jahr: 3 October 2016
• Umfang: 12 S.
• Fussnoten: Gesehen am 07.12.2017
• Titel Quelle: Enthalten in: Annals of hematology
• Ort Quelle: Berlin : Springer, 1955
• Jahr Quelle: 2016
• Band/Heft Quelle: 95(2016), 12, Seite 1931-1942
• ISSN Quelle: 1432-0584
• DOI: doi:10.1007/s00277-016-2810-z
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 156614843X

Abstract

The aim of this clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as biomarker for ATRA therapy in younger adult patients (18-60 years) with acute myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with or without open-label ATRA (45 mg/m2, days 6-8; 15 mg/m2, days 9-21). Two cycles of induction therapy were followed by risk-adapted consolidation with high-dose cytarabine or allogeneic hematopoietic cell transplantation. Due to the open label character of the study, analysis was performed on an intention-to-treat (ITT) and a per-protocol (PP) basis. One thousand one hundred patients were randomized (556, STANDARD; 544, ATRA) with 38 patients treated vice versa. Median follow-up for survival was 5.2 years. ITT analyses revealed no difference between ATRA and STANDARD for the total cohort and for the subset of NPM1-mutated AML with respect to event-free (EFS; p = 0.93, p = 0.17) and overall survival (OS; p = 0.24 and p = 0.32, respectively). Pre-specified PP analyses revealed better EFS in NPM1-mutated AML (p = 0.05) and better OS in the total cohort (p = 0.03). Explorative subgroup analyses on an ITT basis revealed better OS (p = 0.05) in ATRA for genetic low-risk patients according to ELN recommendations. The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2004-004321-95).