The European Commission approved Mylotarg (gemtuzumab ozogamicin) in combination with daunorubicin and cytarabine for the treatment of patients age 15 years and above with previously untreated, de novo, CD33-positive acute myeloid leukemia, except acute promyelocytic leukemia.
The drug is sponsored by Pfizer Inc.
Mylotarg is the first and only AML therapy approved in the European Union that targets CD33, an antigen expressed on AML cells in up to 90% of patients.
The European Commission’s approval of Mylotarg was based on data from an investigator-led, phase III randomized, open-label study (ALFA-0701) in previously untreated, de novo patients. Mylotarg received approval by the FDA in September 2017 for adults with newly diagnosed CD33-positive acute myeloid leukemia, and adults and children 2 years and older with relapsed or refractory CD33-positive AML.
Hepatotoxicity, including life-threatening and sometimes fatal hepatic failure and VOD/SOS, have been reported in patients treated with MYLOTARG. Other special warnings and precautions include myelosuppression and infusion-related reactions.
In the combination therapy study ALFA-0701, clinically relevant serious adverse reactions were hepatotoxicity, including VOD/SOS (3.8%), hemorrhage (9.9%), severe infection (41.2%), and tumour lysis syndrome (1.5%). In monotherapy studies, clinically relevant serious adverse reactions also included infusion related reactions (2.5%), thrombocytopenia (21.7%), and neutropenia (34.3%).
The most common adverse reactions (> 30%) in the combination therapy study were hemorrhage and infection. In monotherapy studies the most common adverse reactions (> 30%) included pyrexia, nausea, infection, chills, hemorrhage, vomiting, thrombocytopenia, fatigue, headache, stomatitis, diarrhea, abdominal pain, and neutropenia.
Mylotarg is an antibody-drug conjugate composed of the cytotoxic agent calicheamicin, attached to a monoclonal antibody targeting CD33, an antigen expressed on the surface of myeloblasts in up to 90 percent of AML patients. When MYLOTARG binds to the CD33 antigen on the cell surface it is absorbed into the cell and calicheamicin is released causing cell death.
Mylotarg was approved by the FDA in September 2017 for adults with newly diagnosed CD33-positive acute myeloid leukemia, and adults and children 2 years and older with relapsed or refractory CD33-positive AML.