1. 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
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Lübbert, Michael, Suciu, Stefan, Hagemeijer, Anne, Rüter, Björn, Platzbecker, Uwe, Giagounidis, Aristoteles, Selleslag, Dominik, Labar, Boris, Germing, Ulrich, Salih, Helmut, Muus, Petra, Pflüger, Karl-Heinz, Schaefer, Hans-Eckart, Bogatyreva, Lioudmila, Aul, Carlo, Witte, Theo, Ganser, Arnold, Becker, Heiko, Huls, Gerwin, and Helm, Lieke
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MYELODYSPLASTIC syndromes , *DECITABINE , *DISEASE progression , *CYTOGENETICS , *KARYOTYPES , *PATIENTS , *THERAPEUTICS , *ANTINEOPLASTIC agents , *CANCER chemotherapy , *LEUKEMIA diagnosis , *THERAPEUTIC use of antimetabolites , *CHROMOSOME abnormalities , *COMPARATIVE studies , *LEUKEMIA , *RESEARCH methodology , *MEDICAL cooperation , *PROGNOSIS , *RESEARCH , *EVALUATION research , *RANDOMIZED controlled trials , *AZACITIDINE , *DIAGNOSIS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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