All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study.

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).

• Authors: 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, German-Austrian Acute Myeloid Leukemia Study Group
• Journal: Annals of hematology (Ann Hematol) Vol. 95 Issue 12 Pg. 1931-1942 (Dec 2016) ISSN: 1432-0584 [Electronic] Germany
• PMID: 27696203 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• NPM1 protein, human
• Nucleophosmin
• Tretinoin

Topics

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Female
• Follow-Up Studies
• Humans
• Induction Chemotherapy (methods, mortality)
• Leukemia, Myeloid, Acute (diagnosis, drug therapy, mortality)
• Male
• Middle Aged
• Nucleophosmin
• Survival Rate (trends)
• Treatment Outcome
• Tretinoin (administration & dosage)
• Young Adult