Gemtuzumab ozogamicin

A humanized anti-CD33 antibody linked to calicheamicin, a potent tumor antibiotic that causes breaks in double-strand DNA that leads to cell death.

Conjugated monoclonal antibody designed to deliver a cytotoxic agent to targeted cells.

Gemtuzumab ozogamicin approved for adults with newly diagnosed CD33 positive AML and adults and children age 2 years and older with relapse/refractory CD33 positive AML.

Binding to CD33 antigen is followed by endocytosis, cleavage of covalent bond between the monoclonal antibody and calicheamicin in lysosomes and release of the calicheamicin.

CD33 is a surface antigen, a glycoprotein, commonly found on the surface of leukemia blast cells.

Release of calicheamicin results in glutathione reduction producing an intermediate agent that causes DNA double strand breaks.

Cytotoxicity of calicheamicin is approximately 1,000 times greater than doxorubicin.

Utilized in various stages of disease, including relapse and recurrent disease.

Effective inpatients with CD33positive AML in first relapse.

zvavorable risk AML patients experience improved outcomes, most notably those who have core-binding factor abnormalities.

31% remission rate in acute myelogenous leukemia, 14% early mortality, and median survival of 5.4 months in younger patients and 5.9 months in older patients.

Analysis of three mulitcenter trials of monotherapy of 9 mg/m2 2 hour infusions in CD33 positive patients associated with a 30% remission rate.

Active in patie4nts over the age of 65 (Nabhan).

Most effective when combined with conventional chemotherapy.

Intravenous infusions may be associated with blood pressure changes, fever, chills, headache and dyspnea.

Allergic reactions can occur and include facial flushing, itching and skin rash.

Associated with myelosuppression, elevated bilirubin, elevated liver function tests, mucositis, nausea, vomiting, cardiac toxicity and liver toxicity.

May be associated with hepatic veno-occlusive disease.

Gemtuzumab ozogamicin (Mylotarg)

Withdrawn from marker 7/10 failing to confirm clinical benefit and associated with fatal induction toxicity.

Reapproved in 2017 for patients 2 years or older with CD33 positive relapsed/refractory AML.

In several studies improved event free survival versus chemotherapy 31% reduction in the risk of death.

Patients with core-binding factor abnormality should receive combination therapy 7+3 with gemutuzumab.

The drug has potentially significant increased risk of cytopenias and liver toxicity including  vasoocclusive disease, which is often seen in the setting of subsequent stem cell transplantation.


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