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FDA Approves Gemtuzumab for Treatment of Acute Myeloid Leukemia

The drug was previously withdrawn from the market in 2010

The FDA has approved gemtuzumab ozogamicin (Mylotarg, Pfizer) for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) whose tumors express the CD33 antigen. The FDA also approved gemtuzumab for the treatment of patients 2 years of age and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment.

Gemtuzumab originally received accelerated approval in May 2000 as a standalone treatment for older patients with CD33-positive AML who had experienced a relapse. It was voluntarily withdrawn from the market in 2010 after subsequent confirmatory trials failed to verify clinical benefit and demonstrated safety concerns, including a high number of early deaths. Today’s approval includes a lower recommended dose, a different schedule in combination with chemotherapy or on its own, and a new patient population.

“We are approving Mylotarg after a careful review of the new dosing regimen, which has shown that the benefits of this treatment outweigh the risk,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a press release. “Mylotarg’s history underscores the importance of examining alternative dosing, scheduling, and administration of therapies for patients with cancer, especially in those who may be most vulnerable to the side effects of treatment.”

AML is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of white blood cells in the bloodstream. The National Cancer Institute estimates that approximately 21,380 people will be diagnosed with AML this year and that 10,590 patients with AML will die of the disease.

Gemtuzumab is a targeted therapy that consists of an antibody connected to an antitumor agent that is toxic to cells. It is thought to work by taking the antitumor agent to the AML cells that express the CD33 antigen, blocking the growth of cancerous cells and causing cell death.

The safety and efficacy of gemtuzumab in combination with chemotherapy for adults were studied in a trial of 271 patients with newly diagnosed CD33-positive AML who were randomized to receive gemtuzumab in combination with daunorubicin and cytarabine or to receive daunorubicin and cytarabine alone. The trial measured event-free survival, including failure to respond to treatment, disease relapse, or death, from the date patients started the trial. Patients who received gemtuzumab in combination with chemotherapy went longer without complications than those who received chemotherapy alone (median, event-free survival, 17.3 months versus 9.5 months).

The safety and efficacy of gemtuzumab as a standalone treatment were studied in two separate trials. The first trial included 237 patients with newly diagnosed AML who could not tolerate or chose not to receive intensive chemotherapy. Patients were randomized to receive treatment with gemtuzumab or best supportive care. The trial measured overall survival (OS). Patients who received gemtuzumab had a median OS of 4.9 months versus 3.6 months for best supportive care. The second trial was a single-arm study that included 57 patients with CD33-positive AML who had experienced one relapse of disease. Patients received a single course of gemtuzumab. The trial measured how many patients achieved a complete remission. Following treatment with gemtuzumab, 26% of patients achieved a complete remission that lasted a median 11.6 months.

Common side effects of gemtuzumab include pyrexia, nausea, infection, vomiting, bleeding, and thrombocytopenia. Severe side effects of gemtuzumab include low blood counts, infections, liver damage, hepatic veno-occlusive disease, infusion-related reactions, and hemorrhage.

The prescribing information for gemtuzumab includes a boxed warning that severe or fatal hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome, occurred in some patients who took gemtuzumab.

Gemtuzumab received an orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

Source: FDA; September 1, 2017.

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