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

作者：Schlenk Richard F^*; Luebbert Michael; Benner Axel; Lamparter Alexander; Krauter Juergen; Herr Wolfgang; Martin Hans; Salih Helmut R; Kuendgen Andrea; Horst Heinz A; Brossart Peter; Goetze Katharina; Nachbaur David; Wattad Mohammed; Koehne Claus Henning; Fiedler Walter; Bentz Martin; Wulf Gerald; Held Gerhard; Hertenstein Bernd; Salwender Hans; Gaidzik Verena I; Schlegelberger Brigitte; Weber Daniela; Doehner Konstanze; Ganser Arnold; Doehner Hartmut

来源：Annals of Hematology, 2016, 95(12): 1931-1942.

DOI：10.1007/s00277-016-2810-z

• Acute myeloid leukemia
• All-trans retinoic acid
• Nucleophosmin-1

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/m(2), days 6-8; 15 mg/m(2), 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).

• 出版日期2016-12