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

Autor: 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
Přispěvatelé: Stem Cell Aging Leukemia and Lymphoma (SALL), Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Rok vydání: 2015
Předmět:
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
Zdroj: Annals of Hematology, 95(2), 191-199. SPRINGER
Annals of Hematology, 95, 191-199
Annals of Hematology, 95, 2, pp. 191-199
ISSN: 1432-0584
0939-5555
Popis: 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.
Databáze: OpenAIRE
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