title: Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study.
abstract: In older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission. The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin (GO) has shown antileukemic remission induction activity in patients with relapsed AML. Patients with AML or refractory anemia with excess blasts in first complete remission attained after intensive induction chemotherapy were randomized between 3 cycles of GO (6 mg/m(2) every 4 weeks) or no postremission therapy (control) to assess whether GO would improve outcome. The 2 treatment groups (113 patients receiving GO vs 119 control patients) were comparable with regard to age (60-78 years, median 67 years), performance status, and cytogenetics. A total of 110 of 113 received at least 1 cycle of GO, and 65 of 113 patients completed the 3 cycles. Premature discontinuation was mainly attributable to incomplete hematologic recovery or intercurrent relapse. Median time to recovery of platelets 50 x 10(9)/L and neutrophils 0.5 x 10(9)/L after GO was 14 days and 20 days. Nonhematologic toxicities were mild overall, but there was 1 toxic death caused by liver failure. There were no significant differences between both treatment groups with regard to relapse probabilities, nonrelapse mortality, overall survival, or disease-free survival (17% vs 16% at 5 years). Postremission treatment with GO in older AML patients does not provide benefits regarding any clinical end points. The HOVON-43 study is registered at The Netherlands Trial Registry (number NTR212) and at http://www.controlled-trials.com as ISRCTN77039377.
authors.affiliation: Erasmus University Medical Center, Rotterdam, The Netherlands. b.lowenberg@erasmusmc.nl
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Joachim
authors.initials: J
authors.lastname: Beck
authors.forename: Carlos
authors.initials: C
authors.lastname: Graux
authors.forename: Wim
authors.initials: W
authors.lastname: van Putten
authors.forename: Harry C
authors.initials: HC
authors.lastname: Schouten
authors.forename: Leo F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: Augustin
authors.initials: A
authors.lastname: Ferrant
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Mojca
authors.initials: M
authors.lastname: Jongen-Lavrencic
authors.forename: Marie
authors.initials: M
authors.lastname: von Lilienfeld-Toal
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Biemond
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Dimitri
authors.initials: D
authors.lastname: Breems
authors.forename: Hilde
authors.initials: H
authors.lastname: de Muijnck
authors.forename: Ron
authors.initials: R
authors.lastname: Schaafsma
authors.forename: Gregor
authors.initials: G
authors.lastname: Verhoef
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: Thomas
authors.initials: T
authors.lastname: Pabst
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
mesh_terms: D000208:Acute Disease; D000367:Age Factors; D000368:Aged; D000617:Aminoglycosides / Q000009:adverse effects / Q000627:therapeutic use*; D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D018572:Disease-Free Survival; D005260:Female; D005334:Fever / Q000139:chemically induced; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D000079982:Gemtuzumab; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D000922:Immunotoxins / Q000009:adverse effects / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D018805:Sepsis / Q000209:etiology; D016019:Survival Analysis
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000922:Immunotoxins; D000079982:Gemtuzumab