1. Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML
- Author
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Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, van Norden, Yvette, Biemond, Bart J, Schouten, Harry C, Spertini, Olivier, Vellenga, Edo, Graux, Carlos, Havelange, Violaine, de Greef, Georgine E, de Weerdt, Okke, Legdeur, Marie-Cecile J C, Kuball, Juergen, Kooy, Marinus van Marwijk, Gjertsen, Bjorn T, Jongen-Lavrencic, Mojca, van de Loosdrecht, Arjan A, van Lammeren-Venema, Daniëlle, Hodossy, Beata, Breems, Dimitri A, Chalandon, Yves, Passweg, Jakob, Valk, Peter J M, Manz, Markus G, Ossenkoppele, Gert J, Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), Swiss Group for Clinical Cancer Research (SAKK), MUMC+: MA Hematologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, CCA - Cancer Treatment and quality of life, Hematology, University of Zurich, Löwenberg, Bob, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), CCA - Cancer Treatment and Quality of Life, and Clinical Haematology
- Subjects
1303 Biochemistry ,PROGNOSIS ,medicine.medical_treatment ,2720 Hematology ,Hematopoietic stem cell transplantation ,Gastroenterology ,Biochemistry ,RECOMMENDATIONS ,1307 Cell Biology ,0302 clinical medicine ,Clofarabine ,610 Medicine & health ,ddc:616 ,Adenine Nucleotides ,Remission Induction ,Induction Chemotherapy ,Hematology ,Middle Aged ,CHEMOTHERAPY ,Chemotherapy regimen ,CYTARABINE ,Survival Rate ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,SURVIVAL ,Nucleophosmin ,medicine.drug ,Adult ,Risk ,medicine.medical_specialty ,Antimetabolites, Antineoplastic ,Adolescent ,Gemtuzumab ozogamicin ,Immunology ,ACUTE MYELOID-LEUKEMIA ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Journal Article ,Humans ,Survival rate ,Aged ,Chemotherapy ,2403 Immunology ,OLDER PATIENTS ,business.industry ,Myelodysplastic syndromes ,Cell Biology ,medicine.disease ,GEMTUZUMAB OZOGAMICIN ,Surgery ,Consolidation Chemotherapy ,10032 Clinic for Oncology and Hematology ,Cytarabine ,Arabinonucleosides ,business ,030215 immunology - Abstract
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
- Published
- 2017