Targeting Cd33positive Acute Myeloid Leukemia

The CD33 antigen is a transmembrane protein expressed on the leukemic cells for the majority of patients with AML.104 This antigen is not expressed on non-hematopoietic cells. These observations make it an appealing target for antibody therapy.105,106 Gemtuzumab ozogamicin is an immunoconjugate of a humanized anti-CD33 monoclonal antibody chemically linked to a semisynthetic derivative of a very potent cytotoxic antitumor antibiotic, calicheamicin.107 (Figure 3-6) A phase I dose-escalation trial in 40 patients with relapsed or refractory AML showed that leukemia was eliminated from the blood and marrow in 8 (20%) patients.108 Subsequently, three multicenter phase II trials were conducted in 142 patients in first relapse with a relatively long first remission duration (median approximately 11 months) and no antecedent hematologic disorder.109 Complete remission, but with incomplete recovery of platelet count to > 100,000, was obtained in 30% of patients. Non-hematologic toxicities were modest and included grade 3 or 4 hyperbilirubinemia in 23%, elevated hepatic transaminases in 17%, and infections in 28%. An hepatic veno-occlusive disease-like syndrome has been reported in a small percentage of patients.110-112 This agent represents a novel delivery technique with modest toxicity. The phase II trials were encouraging, and despite the relatively favorable population of patients, that gemtuzumab ozogamicin has been incorporated into chemotherapy programs for induction with excellent CR rates of 86% after 1 cycle.113,114

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