TY - JOUR
T1 - Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML
AU - Löwenberg, Bob
AU - Pabst, Thomas
AU - Maertens, Johan
AU - van Norden, Yvette
AU - Biemond, Bart J.
AU - Schouten, Harry C.
AU - Spertini, Olivier
AU - Vellenga, Edo
AU - Graux, Carlos
AU - Havelange, Violaine
AU - de Greef, Georgine E
AU - De Weerdt, Okke
AU - Legdeur, Marie-Cecile J C
AU - Kuball, Juergen
AU - van Marwijk Kooy, Marinus
AU - Gjertsen, Bjorn T
AU - Jongen-Lavrencic, Mojca
AU - van de Loosdrecht, Arjan A
AU - van Lammeren-Venema, Daniëlle
AU - Hodossy, Beata
AU - Breems, Dimitri A
AU - Chalandon, Yves
AU - Passweg, Jakob
AU - Valk, Peter J M
AU - Manz, Markus G
AU - Ossenkoppele, Gert J
N1 - Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/3/23
Y1 - 2017/3/23
N2 - 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/m2 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 revealsnodifferences in overall survivalandEFSbetweenthe control (EFS,35%63 [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 riskAML(EFS,26%64 vs40%65 at 4 years;CoxP5.002) and for the intermediate risk genotype NPM1 wild-type/FLT3 without internal-tandem duplications (EFS, 18% 6 5 vs 40% 6 7; Cox P < .001). Clofarabine improves survival in subsets of intermediate-risk AML only. HOVON-102 study is registered at Netherlands Trial Registry #NTR2187.
AB - 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/m2 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 revealsnodifferences in overall survivalandEFSbetweenthe control (EFS,35%63 [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 riskAML(EFS,26%64 vs40%65 at 4 years;CoxP5.002) and for the intermediate risk genotype NPM1 wild-type/FLT3 without internal-tandem duplications (EFS, 18% 6 5 vs 40% 6 7; Cox P < .001). Clofarabine improves survival in subsets of intermediate-risk AML only. HOVON-102 study is registered at Netherlands Trial Registry #NTR2187.
UR - http://www.scopus.com/inward/record.url?scp=85016270969&partnerID=8YFLogxK
U2 - 10.1182/blood-2016-10-740613
DO - 10.1182/blood-2016-10-740613
M3 - Article
C2 - 28049642
SN - 0006-4971
VL - 129
SP - 1636
EP - 1645
JO - Blood
JF - Blood
IS - 12
ER -