title: Early phase I/II trials with gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia.
abstract: Relapsed acute myeloid leukemia (AML) carries a poor prognosis. Treatment options are limited, and their toxicities are substantial. There is an urgent need for novel therapies that are effective and have acceptable side effects. Gemtuzumab ozogamicin (Mylotarg) is an immunoconjugate targeted against CD33, which is expressed on more than 90% of myeloid leukemic blasts. The antibody is attached to calicheamicin, a potent cytotoxic enediyne antibiotic that inhibits DNA synthesis and induces apoptosis. In vitro studies showed excellent activity of gemtuzumab ozogamicin in leukemic cell lines and encouraged the evaluation of this agent in patients. In this review, early phase I/II studies that led to the US Food and Drug Administration approval of this immunoconjugate for older patients with relapsed AML are discussed. Potential adverse events reported with this agent, particularly the recent data of possible veno-occlusive disease and increased hepatotoxicity, are addressed. This agent is currently being investigated in many clinical trials as a front-line approach in previously untreated individuals, and it is likely that it will have many more indications in the near future.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Northwestern University Medical School, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA. c-nabhan@northwestern.edu
authors.forename: Chadi
authors.initials: C
authors.lastname: Nabhan
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
mesh_terms: D000617:Aminoglycosides / Q000627:therapeutic use* / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use* / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D000079982:Gemtuzumab; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D012008:Recurrence; D063268:Sialic Acid Binding Ig-like Lectin 3; D016019:Survival Analysis
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab