Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML.

Détails

ID Serval
serval:BIB_04ADFB38F5B5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML.
Périodique
Blood
Auteur(s)
Löwenberg B., Pabst T., Maertens J., van Norden Y., Biemond B.J., Schouten H.C., Spertini O., Vellenga E., Graux C., Havelange V., de Greef G.E., de Weerdt O., Legdeur M.J., Kuball J., Kooy M.V., Gjertsen B.T., Jongen-Lavrencic M., van de Loosdrecht A.A., van Lammeren-Venema D., Hodossy B., Breems D.A., Chalandon Y., Passweg J., Valk P.J., Manz M.G., Ossenkoppele G.J.
Collaborateur(s)
Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK)
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Statut éditorial
Publié
Date de publication
23/04/2017
Peer-reviewed
Oui
Volume
129
Numéro
12
Pages
1636-1645
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Clofarabine has demonstrated antileukemic activity in acute myeloid leukemia (AML) but has yet to be critically evaluated in younger adults in the frontline with standard chemotherapy. We compared 2 induction regimens in newly diagnosed patients ages 18 to 65 with acute myeloid leukemia (AML)/high-risk myelodysplastic syndromes, that is, idarubicine-cytarabine (cycle I) and amsacrine-cytarabine (cycle II) without or with clofarabine (10 mg/m(2) on days 1-5 of each of both cycles). Consolidation involved chemotherapy with or without hematopoietic stem cell transplantation. Event-free survival (EFS, primary endpoint) and other clinical endpoints and toxicities were assessed. We randomized 402 and 393 evaluable patients to the control or clofarabine induction treatment arms. Complete remission rates (89%) did not differ but were attained faster with clofarabine (66% vs 75% after cycle I). Clofarabine added grades 3 to 4 toxicities and delayed hematological recovery. At a median follow-up of 36 months, the study reveals no differences in overall survival and EFS between the control (EFS, 35% ± 3 [standard error] at 4 years) and clofarabine treatments (38% ± 3) but a markedly reduced relapse rate (44% ± 3 vs 35% ± 3) in favor of clofarabine and an increased death probability in remission (15% ± 2 vs 22% ± 3). In the subgroup analyses, clofarabine improved overall survival and EFS for European Leukemia Net (ELN) 2010 intermediate I prognostic risk AML (EFS, 26% ± 4 vs 40% ± 5 at 4 years; Cox P = .002) and for the intermediate risk genotype NPM1 wild-type/FLT3 without internal-tandem duplications (EFS, 18% ± 5 vs 40% ± 7; Cox P < .001). Clofarabine improves survival in subsets of intermediate-risk AML only. HOVON-102 study is registered at Netherlands Trial Registry #NTR2187.

Pubmed
Web of science
Open Access
Oui
Création de la notice
10/01/2017 18:52
Dernière modification de la notice
08/05/2019 13:52
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