title: Acute and long-term toxicities associated with gemtuzumab ozogamicin (Mylotarg) therapy of acute myeloid leukemia.
abstract: Gemtuzumab ozogamicin (Mylotarg) targets leukemia cells that express CD33 by means of a humanized anti-CD33 monoclonal antibody conjugated to a modified antitumor antibiotic, calicheamicin. The effects of gemtuzumab ozogamicin (given intravenously at a dose of 9 mg/m2 for 2 doses separated by 2 weeks) have been evaluated in 3 phase II studies involving patients (n = 188) with acute myeloid leukemia (AML) in first relapse. Interim analysis has revealed that 30% of patients achieved remission, characterized by < or = 5% blasts in the marrow, neutrophil count > or = 1500/microL, hemoglobin > or = 9 g/dL, and independence from red blood cell and platelet transfusion. Grade 3/4 acute toxicities included nausea or vomiting (11%); elevated serum aminotransferase enzyme (16%) and bilirubin (26%) levels; and infusion-related chills (9%), fever (6%), and hypotension (5%). As predicted with CD33-targeted therapy, most patients had neutropenia (98%) and thrombocytopenia (99%). However, the incidence of grade 3/4 bleeding events (14%) and infection rates (pneumonia, 7%; sepsis, 15%) was low. No patients were reported to have treatment-related cardiotoxicity, cerebellar toxicity, or alopecia. Veno-occlusive disease (VOD) after gemtuzumab ozogamicin treatment (but prior to other therapies) occurred in 2% of patients (4/188), and the VOD-related death rate was < 1% (1/188). Prior hematopoietic stem cell transplant may be a risk factor for VOD (P = 0.002, univariate analysis). Gemtuzumab ozogamicin is a safe and effective treatment in carefully selected patients with AML in first relapse.
authors.affiliation: Department of Clinical Research and Development, Wyeth-Ayerst Research, Philadelphia, PA 19101, USA. leopoll@war.wyeth.com
authors.forename: Lance H
authors.initials: LH
authors.lastname: Leopold
authors.forename: Mark S
authors.initials: MS
authors.lastname: Berger
authors.forename: Jay
authors.initials: J
authors.lastname: Feingold
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D000079982:Gemtuzumab; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced; D006801:Humans; D000922:Immunotoxins / Q000633:toxicity; D007262:Infusions, Intravenous / Q000009:adverse effects; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects / Q000473:pathology
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000922:Immunotoxins; D000079982:Gemtuzumab