Through the years gemtuzumab ozogamicin (GO) has moved from a panacea in the treatment of acute myeloid leukemia (AML) to a pariah and back again. Early promise of targeted therapy with accelerated approval in the United States in 2000 gave way to fear over increased toxicity in the absence of efficacy, which subsequently resulted in the drug manufacturer voluntarily withdrawing GO from the market in 2010. We outline the history of GO in terms of initial drug development and early clinical trials that ultimately led the way to GO frontline use in AML based on a series of Phase III studies. Among these studies, we discuss the similarities and differences in terms of dosing, frequency, response rates, and toxicities that ultimately led to the re-approval of GO in 2017 based on efficacy, particularly in patients with core-binding factor (CBF) leukemia. Herein, we also review the clinical efficacy of GO in the frontline treatment of acute promyelocytic leukemia, which is based on either initial patient high-risk disease or potential co-morbidities that preclude the use of arsenic trioxide (ATO). Finally, we assess the current evidence for biomarkers aside from initial cytogenetics that may predict a favorable response to GO.
Keywords: AML; core binding factor; leukemia; treatment.