Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study.
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.
Löwenberg
Bob
B
Erasmus University Medical Center, Rotterdam, The Netherlands. b.lowenberg@erasmusmc.nl
Beck
Joachim
J
Graux
Carlos
C
van Putten
Wim
W
Schouten
Harry C
HC
Verdonck
Leo F
LF
Ferrant
Augustin
A
Sonneveld
Pieter
P
Jongen-Lavrencic
Mojca
M
von Lilienfeld-Toal
Marie
M
Biemond
Bart J
BJ
Vellenga
Edo
E
Breems
Dimitri
D
de Muijnck
Hilde
H
Schaafsma
Ron
R
Verhoef
Gregor
G
Döhner
Hartmut
H
Gratwohl
Alois
A
Pabst
Thomas
T
Ossenkoppele
Gert J
GJ
Maertens
Johan
J
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
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000922:Immunotoxins; D000079982:Gemtuzumab