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Ann Hematol. 2016 Jan;95(2):191-9. doi: 10.1007/s00277-015-2547-0. Epub 2015 Nov 23.

Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group.

Author information

1
Division of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg Medical Center, Freiburg, Germany. michael.luebbert@uniklinik-freiburg.de.
2
European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium.
3
Department of Human Genetics, University Hospital, University of Leuven, Leuven, Belgium.
4
Division of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg Medical Center, Freiburg, Germany.
5
Department of Hematology and Oncology, University of Dresden, Dresden, Germany.
6
Department of Hematology and Oncology, Marienhospital, Düsseldorf, Germany.
7
Department of Hematology, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium.
8
University Hospital Center Rebro, Zagreb, Croatia.
9
Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.
10
Department of Hematology/Oncology, Eberhard Karls University, Tübingen, Germany.
11
Department of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
12
Department of Medicine II, DIAKO Bremen, Bremen, Germany.
13
Institute of Pathology, University of Freiburg, Freiburg, Germany.
14
Institute for Medical Biometry and Medical Informatics, University of Freiburg, Freiburg, Germany.
15
Hematology, Oncology, and Clinical Immunology, St Johannes Hospital, Duisburg, Germany.
16
Department of Tumor Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
17
Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
18
Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands.
19
C.H.U. Sart-Tilman, Liège, Belgium.
20
UPMC, UMRS 872 and Saint-Antoine Hospital, AP-HP, Paris, France.
21
Department of Hematology, Haga Hospital, The Hague, The Netherlands.

Abstract

In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC.

KEYWORDS:

Adverse cytogenetics; Azacytidine; Elderly patients; Epigenetic therapy; Hypomethylating agents; Monosomal karyotype

PMID:
26596971
DOI:
10.1007/s00277-015-2547-0
[Indexed for MEDLINE]
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