FDA Issues New Safety Warnings on Brentuximab, Including Risk of Rare Brain Infection

The FDA and Seattle Genetics announced that new warning labels would be issued for brentuximab vedotin.

The FDA and Seattle Genetics announced that new warning labels would be issued for brentuximab vedotin (Adcetris) after additional studies revealed a slightly increased risk for a rare but potentially fatal brain infection, along with other warnings based on clinical data.

Two additional cases of progressive multifocal leukoencephalopathy (PML) have been reported since the FDA approved brentuximab vedotin in August 2011 for treating Hodgkin lymphoma patients and patients with systemic anaplastic large cell lymphoma. Since the FDA approved brentuximab vedotin, approximately 2000 patients with these hematologic diseases have been treated with the drug.

PML is caused when the John Cunningham virus—a virus that resides latently in 40% to 80% of adults—is reactivated. The progressive, demyelinating disease of the central nervous system often causes disability, and 30% to 50% of patients die within a few months of their initial diagnosis, according to the National Institutes of Health. It is also a relatively rare disease. PML had been reported in one instance during clinical testing of brentuximab vedotin prior to its approval in August.

In addition to the warning regarding PML, a contraindication warning was also issued advising against taking brentuximab vedotin with another cancer drug, bleomycin. In a clinical trial comparing the use of brentuximab vedotin to other anti-cancer agents, it was shown that patients who received the drug with bleomycin had a 40% frequency of developing pulmonary toxicity, compared to 10% to 25% frequency in patients who only received bleomycin.

“Our first priority is patient safety,” said Thomas C. Reynolds, MD, PhD, Chief Medical Officer of Seattle Genetics, in a release. “By developing these agreed upon label updates with the FDA regarding PML and the contraindication with bleomycin, we aim to heighten awareness among healthcare professionals in order to most safely treat their patients with Adcetris.”

Brentuximab vedotin is the first drug the FDA has approved for treating patients with Hodgkin lymphoma since 1977. It is an antibody-drug conjugate that selectively targets CD30, a cell membrane protein overexpressed in the disorder.

The FDA approved brentuximab vedotin for patients with Hodgkin lymphoma whose disease has progressed after autologous stem cell transplant or after 2 prior chemotherapy treatments for those who cannot receive a transplant. It also may be used for patients with anaplastic large cell lymphoma whose disease has progressed after 1 chemotherapy treatment.