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

被引：85

作者：

Lowenberg, Bob ^{[1
]}

Pabst, Thomas ^{[2
]}

Maertens, Johan ^{[3
]}

van Norden, Yvette ^{[4
]}

Biemond, Bart J. ^{[5
]}

Schouten, Harry C. ^{[6
]}

Spertini, Olivier ^{[7
]}

Vellenga, Edo ^{[8
]}

Graux, Carlos ^{[9
]}

Havelange, Violaine ^{[10
]}

de Greef, Georgine E. ^{[1
]}

de Weerdt, Okke ^{[11
]}

Legdeur, Marie-Cecile J. C. ^{[12
]}

Kuball, Juergen ^{[13
]}

Kooy, Marinus van Marwijk ^{[14
]}

Gjertsen, Bjorn T. ^{[15
]}

Jongen-Lavrencic, Mojca ^{[1
]}

de Loosdrecht, Arjan A. van ^{[16
]}

van Lammeren-Venema, Danielle ^{[17
]}

Hodossy, Beata ^{[18
]}

Breems, Dimitri A. ^{[19
]}

Chalandon, Yves ^{[20
]}

Passweg, Jakob ^{[21
]}

Valk, Peter J. M. ^{[1
]}

Manz, Markus G. ^{[22
,23
]}

Ossenkoppele, Gert J. ^{[16
]}

机构：

[1] Erasmus Univ Med Ctr MC, Dept Hematol, POB 2040, NL-3000 CA Rotterdam, Netherlands

[2] Inselspital Bern, Bern, Switzerland

[3] Univ Hosp Gasthuisberg, Dept Hematol, Leuven, Belgium

[4] Erasmus Univ MC Canc Inst, HOVON Data Ctr, Rotterdam, Netherlands

[5] Acad Med Ctr, Dept Hematol, Amsterdam, Netherlands

[6] Univ Hosp, Dept Hematol, Maastricht, Netherlands

[7] Univ Hosp, Dept Hematol, Lausanne, Switzerland

[8] Univ Groningen, Univ Med Ctr Groningen, Dept Hematol, Groningen, Netherlands

[9] UCL Namur Godinne, Yvoir, Belgium

[10] Dept Hematol, Hop St Luc, Brussels, Belgium

[11] St Antonius Hosp, Nieuwegein, Netherlands

[12] Med Spectrum Twente, Enschede, Netherlands

[13] Univ Med Ctr, Dept Hematol, Utrecht, Netherlands

[14] Isala Hosp, Zwolle, Netherlands

[15] Haukeland Hosp, Bergen, Norway

[16] Vrije Univ Amsterdam Med Ctr, Dept Hematol, Amsterdam, Netherlands

[17] Haga Hosp, The Hague, Netherlands

[18] Hop Citadelle, Liege, Belgium

[19] Ziekenhuis Netwerk Antwerpen, Antwerp, Belgium

[20] Univ Hosp, Dept Hematol, Geneva, Switzerland

[21] Univ Geneva, Dept Hematol, Geneva, Switzerland

[22] Univ Hosp, Dept Hematol, Basel, Switzerland

[23] Univ Hosp, Dept Hematol, Zurich, Switzerland

来源：

BLOOD | 2017年 / 129卷 / 12期

关键词：

ACUTE MYELOID-LEUKEMIA; OLDER PATIENTS; GEMTUZUMAB OZOGAMICIN; CYTARABINE; RECOMMENDATIONS; CHEMOTHERAPY; PROGNOSIS; SURVIVAL;

D O I：

10.1182/blood-2016-10-740613

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 revealsnodifferences in overall survival and EFS between the 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% +/- 4 vs40% +/- 5 at 4 years; CoxP5.002) 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.

引用

页码：1636 / 1645

页数：10

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