title: Gemtuzumab ozogamicin in acute myeloid leukemia revisited.
abstract: BACKGROUND
  Gemtuzumab ozogamicin (GO) is a combination of calicheamicin and a recombinant humanized IgG4 antibody directed against CD33. From 2000 to 2010, it was approved by the FDA for treatment of relapsed, older patients with CD33(+) acute myeloid leukemia (AML). After withdrawal from the market, several trials have provided new evidence on the safety and clinical efficacy of GO.
  
  
  METHODS
  In this review, we discuss pharmacological and clinical aspects of GO. GO was found to show benefit in AML patients as adjunct to intensive chemotherapy when it was given in parallel to induction therapy. The benefit was restricted to patients with a favorable- or an intermediate-risk cytogenetic profile. Higher doses of GO above 6 mg/m(2) per administration were associated with increased toxicity without survival benefit, whereas repetitive doses of 3 mg/m(2) resulting in cumulative doses of 9 mg/m(2) were well tolerated. Predictive markers for response to GO other than the cytogenetic profile and P-glycoprotein activity are still missing.
  
  
  CONCLUSIONS
  GO as adjunct and in parallel to intensive induction chemotherapy does significantly improve survival end points in AML patients with favorable/intermediate-risk cytogenetics. A dose of 3 mg/m(2) per administration appears safer compared with 6 mg/m(2) and even 9 mg/m(2).
authors.affiliation: Hannover Medical School, Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation , Carl-Neuberg-Str. 1, 30625, Hannover , Germany.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Thol
authors.forename: Richard F
authors.initials: RF
authors.lastname: Schlenk
mesh_terms: D000367:Age Factors; D000617:Aminoglycosides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001374:Azacitidine / Q000008:administration & dosage; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology; D002986:Clinical Trials as Topic; D000079982:Gemtuzumab; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D012008:Recurrence; D017211:Treatment Failure
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D000079982:Gemtuzumab; D001374:Azacitidine; D006918:Hydroxyurea
keywords: CD33; acute myeloid leukemia; cytogenetic risk group; gemtuzumab ozogamicin