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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Lubbert, M., Suciu, S., Hagemeijer, A., Ruter, B., Platzbecker, U., Giagounidis, A., Selleslag, D., Labar, B., Germing, U., Salih, H.R., Muus, P., Pfluger, K.H., Schaefer, H.E., Bogatyreva, L., Aul, C., Witte, T.J.M. de, Ganser, A., Becker, H., Huls, G.A., Helm, L. van der, Vellenga, E., Baron, F., Marie, J.P., Wijermans, P.W., Group, E.L., German, M.D.S.S.G. the, Stem Cell Aging Leukemia and Lymphoma (SALL), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,NEWLY-DIAGNOSED AML ,Monosomy ,0302 clinical medicine ,Risk Factors ,Germany ,CONVENTIONAL CARE REGIMENS ,ELDERLY-PATIENTS ,Aged, 80 and over ,Leukemia ,Azacytidine ,Hazard ratio ,Hematology ,General Medicine ,Middle Aged ,030220 oncology & carcinogenesis ,Azacitidine ,Disease Progression ,Female ,medicine.drug ,Antimetabolites, Antineoplastic ,medicine.medical_specialty ,MYELODYSPLASTIC SYNDROME MDS ,Decitabine ,Hypomethylating agents ,Subgroup analysis ,ACUTE MYELOID-LEUKEMIA ,Disease-Free Survival ,Adverse cytogenetics ,03 medical and health sciences ,POOR-PROGNOSIS ,Internal medicine ,SUPPORTIVE CARE ,medicine ,Humans ,Progression-free survival ,Aged ,RESPONSE CRITERIA ,Epigenetic therapy ,INTERNATIONAL WORKING GROUP ,business.industry ,Myelodysplastic syndromes ,Monosomal karyotype ,LOW-DOSE DECITABINE ,medicine.disease ,Elderly patients ,030104 developmental biology ,Hypomethylating agent ,Myelodysplastic Syndromes ,Immunology ,business - Abstract
Item does not contain fulltext 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 (Lubbert 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.
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- 2015