Gemtuzumab Ozogamicin (CMA-676, Mylotarg) for the treatment of CD33+ acute myeloid leukemia.
Gemtuzumab Ozogamicin (GO, CMA-676) is a monoclonal antibody against the cellular surface antigen CD33 conjugated with the cytotoxic antibiotic calicheamicin. In the beginning of 2000 it obtained US Food and Drug Administration approval for the treatment of refractory acute myeloid leukemia (AML) expressing CD33 in patients older than 60 years who are not candidates for other chemotherapy. After ligation with the CD33 on the cell surface, GO is internalized and hydrolyzed. Its two components are released into the cytoplasm and calicheamicin enters the nucleus where it associates with the DNA, causing double helix breaks and finally cell death. GO is in general well tolerated. The most frequent adverse effect observed is myelotoxicity, with prolonged neutropenia and thrombocytopenia. Veno-occlusive disease of the liver is a less frequent but severe adverse effect. A phase II study points towards a percentage of overall hematologic response around 30% in the setting of refractory or relapsed disease. Future phase III trials will show the most suitable place of GO in the treatment of AML.
Voutsadakis
Ioannis A
IA
Service d'Hématologie, Department of Medicine and INSERM U487, Institut Gustave-Roussy, 94805 Villejuif, France. voutsadakis@igr.fr
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D000079982:Gemtuzumab; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D063268:Sialic Acid Binding Ig-like Lectin 3
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; 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