Current use and future development of gemtuzumab ozogamicin.

The antigen CD33 is expressed on blast cells in 80% to 90% of acute myeloid leukemia (AML) cases but, importantly, is not expressed on pluripotent hematopoietic stem cells or on nonhematologic cells. Gemtuzumab ozogamicin (CMA-676) uses a recombinant humanized anti-CD33 monoclonal IgG4 antibody to deliver the potent cytotoxin, calicheamicin, into cells. Three multicenter trials have evaluated the efficacy and safety of gemtuzumab ozogamicin as a single agent in 142 patients with CD33+ AML in untreated first relapse. The median age was 61 years (range, 22 to 84 years), none had prior myelodysplasia, and all had had a first complete remission lasting > or = 3 months. Two doses of 9 mg/m2 were given 14 days apart by 2-hour intravenous infusion. The overall response rate was 30% (ie, < or = 5% blasts remaining in the bone marrow, neutrophils > or = 1,500/microL, and red blood cell and platelet transfusion independence). There was no significant difference in response rate between patients less than 60 years of age and those > or = 60 years old (34% v 26%, respectively) or between patients whose first remission had lasted less than 12 months or > or = 12 months (28% v 32%, respectively). Overall survival was 31% at 1 year; median survival was 5.9 months. Median relapse-free survival was 6.8 months. An infusion-related syndrome (chills, fever, rigors, nausea, hypotension, and pain) was common. Severe myelosuppression occurred in all patients, but severe mucositis (4%) and infections (23%) were relatively infrequent. Severe hyperbilirubinemia (23%) and elevated hepatic transaminases (18%) were usually transient. Among all 142 patients, the median total hospitalization was 24 days; 16% of patients required < or = 7 days in hospital. Additional studies are currently evaluating gemtuzumab ozogamicin in combination with, or as an alternative to, other standard AML chemotherapy. Copyright 2001 by W.B. Saunders Company.