Gemtuzumab ozogamicin in acute myeloid leukemia revisited.

INTRODUCTION: Gemtuzumab ozogamicin (GO) is a combination of calicheamicin and a recombinant humanized IgG4 antibody directed against CD33. From 2000 to 2010, it was approved by the FDA for treatment of relapsed, older patients with CD33(+) acute myeloid leukemia (AML). After withdrawal from the market, several trials have provided new evidence on the safety and clinical efficacy of GO. AREAS COVERED: In this review, we discuss pharmacological and clinical aspects of GO. GO was found to show benefit in AML patients as adjunct to intensive chemotherapy when it was given in parallel to induction therapy. The benefit was restricted to patients with a favorable- or an intermediate-risk cytogenetic profile. Higher doses of GO above 6 mg/m(2) per administration were associated with increased toxicity without survival benefit, whereas repetitive doses of 3 mg/m(2) resulting in cumulative doses of 9 mg/m(2) were well tolerated. Predictive markers for response to GO other than the cytogenetic profile and P-glycoprotein activity are still missing. EXPERT OPINION: GO as adjunct and in parallel to intensive induction chemotherapy does significantly improve survival end points in AML patients with favorable/intermediate-risk cytogenetics. A dose of 3 mg/m(2) per administration appears safer compared with 6 mg/m(2) and even 9 mg/m(2).