Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG)
In the European Organisation for Research and Treatment of Cancer (EORTC)/GMDSSG phase III trial 06011, we compared decitabine (15 mg/m2 every 8 h for 3 days) with best supportive care (BSC) in patients ≥60 years with myelodysplastic syndromes (MDS) by French-American-British (FAB) criteria. Here, we reinvestigate trial 06011 for the activity and efficacy specifically in patients with refractory anemia with excess blasts in transformation (RAEBt). Response rates in the decitabine arm (N = 40) were as follows: complete or partial remission, 15 %; hematologic improvement, 15 %; resistant disease, 30 %. RAEBt patients in the decitabine arm had longer progression-free survival (PFS; hazard ratio (HR) 0.30, 95 % confidence interval (CI) 0.18–0.51; median, 6.2 vs 2.8 months) and overall survival (OS; HR 0.68, 95 % CI 0.42–1.11; median, 8.0 vs 6.0 months) than in the BSC arm (N = 35). Censoring at allogeneic hematopoietic stem cell transplantation, the OS difference between the treatment groups increased, particularly among patients aged 60–74 years (HR 0.48, 95 % CI 0.26–0.89). After regrouping the study cohort according to World Health Organization (WHO) criteria, patients with acute myeloid leukemia (AML) (i.e., ≥20 % blasts) in the decitabine arm (N = 27) also had longer PFS than in the BSC arm (N = 23) (HR 0.46, 95 % CI 0.26–0.83; median, 6.2 vs 2.8 months). In conclusion, 3-day decitabine displays clinical activity and efficacy in MDS and/or AML with 5–30 % blood or 20–30 % marrow blasts.
KeywordsRAEBt MDS AML Leukemia Allogeneic transplantation Epigenetic therapy
We thank the following additional EORTC Headquarters staff who worked on this study: Christine de Balincourt, Edith Bastiaens, Caroline Gilotay, Ann Marinus, Liv Meert, Thomas Vandenberghe, and Christine Waterkeyn.
The study was supported by an educational grant from MGI Pharma and Johnson & Johnson. The publication was supported by the EORTC Cancer Research Fund.
Conflict of interest
Personal financial interests: none. Honoraria: U.P., Celgene, Novartis, Amgen; A.G., Celgene; D.S., Celgene, Novartis, Amgen; B.L., Novartis, MSD; U.G., MDS Register Düsseldorf, Johnson & Johnson; H.R.S., Celgene, Novartis; A.G., Genzyme. Funding: U.P., Celgene, Novartis; U.G., MDS Register Düsseldorf; A.G., Novartis. M.L., Janssen-Cilag, Celgene, Teva. Employment: B.H.R., Böhringer-Ingelheim. Patent rights: none. Consultancy Work: U.P., Celgene, Amgen, Novartis; A.G., Celgene; D.S., Celgene, Novartis, Amgen; H.R.S., Novartis, Amgen, BMS; and A.G., Celgene, Novartis.
Conception and design: H.B., S.S., A.Gi., P.M., A.Ga., C.A., T.d.W., and P.W.W.; provision of study materials or patients: B.H.R., U.P., A.Gi., D.S., B.L., U.G., H.R.S., P.M., K.-H.P., A.Ga., C.A., T.d.W., P.W.W., and M.L.; collection and assembly of data: S.S., B.H.R., U.P., A.Gi., D.S., U.G., P.M., K.-H.P., A.H., and M.L.; data analysis and interpretation: H.B., S.S., B.H.R., P.M., A.H., H.-E.S., V.F., F.B., T.d.W., P.W.W., and M.L.; drafting of the manuscript: H.B., S.S., and M.L.; and critical review and final approval of the manuscript: H.B., S.S., B.H.R., U.P., A.Gi., D.S., B.L., U.G., H.S., P.M., K.-H.P., A.H., H.-E.S., V.F., F.B., A.Ga., C.A., T.d.W., P.W.W., and M.L.
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