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Leukemia. 2018 Dec;32(12):2546-2557. doi: 10.1038/s41375-018-0257-z. Epub 2018 Oct 1.

Cytogenetics and gene mutations influence survival in older patients with acute myeloid leukemia treated with azacitidine or conventional care.

Author information

1
Ulm University Hospital, Ulm, Germany. hartmut.doehner@uniklinik-ulm.de.
2
Ulm University Hospital, Ulm, Germany.
3
Celgene Corporation, Summit, NJ, United States.
4
Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Melbourne, and University of Melbourne, Parkville, Australia.
5
University of Toronto, Toronto, ON, Canada.
6
Dana-Farber Cancer Institute, Boston, MA, United States.
7
Hospital Central de Asturias, Oviedo, Spain.
8
Universitätsklinikum Halle (Saale), Halle, Germany.
9
AOU Careggi, University of Florence, Florence, Italy.
10
University of Oxford, Oxford, United Kingdom.
11
Charité University Medicine, Berlin, Germany.
12
Hôpital Saint Louis, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.

Abstract

Older patients with newly diagnosed acute myeloid leukemia (AML) in the phase 3 AZA-AML-001 study were evaluated at entry for cytogenetic abnormalities, and a subgroup of patients was assessed for gene mutations. Patients received azacitidine 75 mg/m2/day x7 days (n = 240) or conventional care regimens (CCR; n = 245): intensive chemotherapy, low-dose cytarabine, or best supportive care only. Overall survival (OS) was assessed for patients with common (occurring in ≥10% of patients) cytogenetic abnormalities and karyotypes, and for patients with recurring gene mutations. There was a significant OS improvement with azacitidine vs CCR for patients with European LeukemiaNet-defined Adverse karyotype (HR 0.71 [95%CI 0.51-0.99]; P = 0.046). Azacitidine-treated patients with -5/5q-, -7/7q-, or 17p abnormalities, or with monosomal or complex karyotypes, had a 31-46% reduced risk of death vs CCR. The most frequent gene mutations were DNMT3A (27%), TET2 (25%), IDH2 (23% [R140, 15%; R172, 8%]), and TP53 (21%). Compared with wild-type, OS was significantly reduced among CCR-treated patients with TP53 or NRAS mutations and azacitidine-treated patients with FLT3 or TET2 mutations. Azacitidine may be a preferred treatment for older patients with AML with Adverse-risk cytogenetics, particularly those with chromosome 5, 7, and/or 17 abnormalities and complex or monosomal karyotypes. The influence of gene mutations in azacitidine-treated patients warrants further study.

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