Information about Gemtuzumab
Liver safety of Gemtuzumab
Gemtuzumab ozogamicin has been linked to transient serum enzyme elevations during therapy and not uncommon instances of acute sinusoidal obstruction syndrome which can be severe and even fatal.
Mechanism of action of Gemtuzumab
Gemtuzumab (jem tooz’ ue mab) ozogamicin (oh” zoe ga mye’ sin) is a humanized monoclonal IgG4 antibody to the human CD33 cell surface marker which is highly expressed on acute myelogenous leukemia cells. The monoclonal antibody is conjugated to a cytotoxic molecule, ozogamicin. When gemtuzumab binds to CD33, it is inteRNAlized and the ozogamicin is released by the action of lysosomal enzymes on the linker molecule that joins the monoclonal antibody and cytotoxic molecule. The intracellular ozogamicin results in apoptotic cell death. This monoclonal antibody conjugate has been shown to be effective in inducing remissions in refractory acute myelogenous leukemia in patients over the age of 60 years and was given accelerated approval for this indication in the United States in 2000.
A subsequent randomized controlled trial, however, showed that the mortality rate was higher with gemtuzumab ozogamicin than with conventional therapy and the monoclonal antibody conjugate was withdrawn from use in 2010. Further studies suggested that a modified dosing schedule [total of 9 mg/m2 given over days 1 and 4 or days 1, 4 and 7 was effective in prolonging event-free survival in patients with acute myelogenous leukemia and had a lower rate of severe hepatic injury than regimens using the 9 mg/m2 dose over one day. Accordingly, gemtuzumab ozogamicin was approved and reintroduced as a therapy of acute myelogenous leukemia in 2017.
Dosage and administration for Gemtuzumab
Gemtuzumab ozogamicin is available in powder for reconstitution in single dose vials of 4.5 mg under the brand name Mylotarg. The typical recommended dose regimen for induction is 3 mg/m2 on days 1, 4 and 7 by intravenous infusion over 2 hours. Gemtuzumab ozogamicin can be given by itself or in combination with daunorubicin and cytarabine. Doses for continuation are generally a single dose of 3 mg/meter squared with each course.
Side effects of Gemtuzumab
Common side effects included infusion reactions with fever, nausea, chills, hypotension and shortness of breath and subsequent adverse events of neutropenia and thrombocytopenia. Less common, but serious side effects included anaphylactic reactions, severe neutropenia, infections and acute hepatic failure. Gemtumuzumab ozogamicin should be administered only by physicians with training and expertise in cancer chemotherapy and management of its potential adverse effects.