CD33 Expression and Gentuzumab Ozogamicin in Acute Myeloid Leukemia: Two Sides of the Same Coin

Simple Summary Roughly 85–90% of adult and pediatric acute myeloid leukemia (AML) are CD33-positive. Gemtuzumab ozogamicin (GO), a humanized murine IgG4 anti-CD33 antibody, is the first target therapy approved in AML therapeutic scenario. This review focuses on current biological information and clinical data from several studies investigating the use of GO in patients with AML. Over the years, flow cytometry, cytogenetics, molecular techniques, and genotyping studies of CD33 SNPs have provided a comprehensive analysis of promising biomarkers for GO responses and have potentially helped to identify subgroups of patients that may benefit from GO addition to standard chemotherapies. Increased understanding of molecular mutations, altered intracellular pathways, and their potential relationship with CD33 expression may open new therapeutic landscapes based on combinatorial regimens in an AML scenario. Abstract Acute myeloid leukemia (AML), the most frequent acute leukemia in adults, has been historically treated with infusional cytarabine (ara-c) + daunorubicin (3 + 7) for at least 40 years. The first “target therapy” to be introduced was the monoclonal anti-CD33 gemtuzumab ozogamicin (GO) in 2004. Unfortunately, in 2010 it was voluntarily withdrawn from the market both for safety reasons related to potential liver toxicity and veno-occlusive disease (VOD) and because clinical studies failed to confirm the clinical benefit during induction and maintenance. Seven years later, GO was re-approved based on new data, including insights into its mechanism of action on its target receptor CD33 expressed on myeloid cells. The present review focuses on current biological information and clinical data from several studies investigating GO. Cytogenetic, molecular, and immunophenotypic data are now able to predict the potential positive advantages of GO, with the exception of high-risk AML patients who do not seem to benefit. GO can be considered a ‘repurposed drug’ that could be beneficial for some patients with AML, mostly in combination with new drugs already approved or currently in testing.