Mylotarg Now Approved for the Treatment of Patients with CD33-Positive AML

FDA Approvals, News & Updates


On September 1, 2017, the FDA approved gemtuzumab ozogamicin (Mylotarg; Pfi­zer) for the treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia (AML), as well as patients aged ≥2 years with relapsed or refractory CD33-positive AML. It is approved as an orphan drug for this indication.

Gemtuzumab ozogamicin was originally approved in 2000 as monotherapy for older patients with relapsed, CD33-positive AML. However, after confirmatory trials failed to verify the drug’s clinical benefits and raised concerns about early death, the manufacturer voluntarily withdrew the drug from the market. The new FDA approval for gem­tuzumab ozogamicin is based on a lower recommended dose and a new dosing schedule (in combination with chemotherapy or as monotherapy), and includes 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. 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,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence.

The FDA approval was based on 3 clinical trials. One study included 271 patients with newly diagnosed CD33-positive AML who were randomized to gemtuzumab ozogamicin, with or without chemotherapy. The event-free survival was 17.3 months with gemtuzumab ozogamicin alone versus 9.5 months with gemtuzumab ozogamicin plus chemotherapy.

The second study included 237 patients with newly diagnosed AML and compared gemtuzumab ozogamicin with best supportive care; the median overall survival was 4.9 months with gemtuzumab ozogamicin versus 3.6 months with best supportive therapy. The third study included 57 patients with relapsed, CD33-positive AML; of these, 26% of the patients achieved complete remission lasting a median of 11.6 months.

The common side effects reported with gemtuzumab ozogamicin include pyrexia, nausea, infection, vomiting, hemorrhage, thrombocytopenia, stomatitis, constipation, rash, headache, elevated liver function, and neutropenia. Severe side effects include low blood counts, infections, liver damage, hepatic veno-occlusive disease (VOD), infusion-related reactions, and hemorrhage. Gemtuzumab ozogamicin was approved with a boxed warning about the risk for severe or fatal hepatotoxicity, including VOD or sinusoidal obstruction syndrome. Pregnant women should not use this drug.