Boxed Warning On Brain Infection Added To Adcetris Label

A boxed warning on brain infection has been added to the Adcetris label, the U.S. Food and Drug Administration (FDA) just announced. It seems, said the FDA, that two additional cases of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection that can result in death, have been reported with the lymphoma drug, Adcetris (brentuximab vedotin).

Adcetris was approval in August 2011 for the treatment of Hodgkin Lymphoma (HL), a rare lymphoma known as systemic anaplastic large cell lymphoma. Adcetris is also an antibody-drug conjugate that combines an antibody and drug and enables the antibody to direct the drug to a target on lymphoma cells known as CD30. Since its approval, some 2,000 patients, worldwide, have received treatment with Adcetris. At that time of its approval, one case of PML was described in the label’s Warnings and Precautions section, the FDA said

The signs and symptoms of PML may develop over several weeks or months and include mood changes; unusual behavior; confusion; thinking problems; loss of memory; changes in vision, speech, or walking; and decreased strength or weakness on one side of the body.

The FDA recommends that patients who develop any signs and symptoms of PML notify their healthcare professional immediately and that healthcare professionals should hold Adcetris dosing if PML is suspected, discontinuing Adcetris if a diagnosis of PML is confirmed. The agency also recommends that healthcare professionals refer to the current Adcetris drug label for the latest prescribing recommendations. Evaluation of PML may involve neurologist consultation, brain magnetic resonance imaging (MRI), and/or lumbar puncture with analysis of cerebrospinal fluid by polymerase chain reaction for John Cunningham virus (JC virus), and/or brain biopsy.

To date, three patients have developed PML while receiving treatment with Adcetris. A 48-year-old man with HL was diagnosed with PML after his third Adcetris dose when he presented with left-sided weakness and slurred speech. Cerebrospinal fluid was positive for JC virus. The man’s condition deteriorated rapidly until his death, which occurred within four weeks of symptom onset.

A 50-year-old man with HL was diagnosed with PML after eight cycles of Adcetris, when he with complaints of speech changes, difficulty writing with his right hand, and right lower extremity weakness; he exhibited poor coordination, poor balance, and left-sided sensory deficits. An MRI was inconclusive and cerebrospinal fluid analyses were negative for JC virus in an early neurologic work-up; however, a spinal cord lesion biopsy tested positive for JC virus. His neurological condition continues to worsen.

A 38-year-old female patient with a history of Stage IV cutaneous anaplastic large cell lymphoma (ALCL) was diagnosed with PML after the second dose of Adcetris when she complained of inability to read or find words to express herself, memory lapses, and slight loss of balance. A brain MRI revealed a demyelinating process and a brain biopsy was positive for JC virus.

Also, a new contraindication warning against use of Adcetris with the cancer drug bleomycin is being added to the drug label over an increased risk of pulmonary (lung) toxicity. The agency notes that patients receiving Adcetris in combination with bleomycin should speak with healthcare professional about stopping this combination of medications.

This entry was posted in Pharmaceuticals. Bookmark the permalink.

© 2005-2016 Parker Waichman LLP ®. All Rights Reserved.