Is Anti-PD-1 Therapy Linked with Neurological Complications?

Clinicians should watch for the emergence of neurological adverse events in patients treated with anti-programmed death 1 (PD-1) therapy, Mayo Clinic researchers warned, after their investigation found neurological symptoms occurred in nearly 3% of patients.

“The time of onset is unpredictable, and evolution may be rapid and life-threatening. Prompt recognition and discontinuation of anti-PD-1 therapy is recommended,” researchers wrote online in JAMA Neurology (doi: 10.1001/jamaneurol.2017.1912). “In some cases, immune rescue treatment may be required.”

For the retrospective study, researchers used the Mayo Cancer Pharmacy Database to identify all patients treated with pembrolizumab or nivolumab from the drugs’ 2014 US Food and Drug Administration approval dates through May 19, 2016. Patients who developed neurological symptoms within 12 months of anti-PD-1 therapy were included only if the complications were not attributable to metastatic disease or other cancer-related treatments.

Among 347 patients treated with anti-PD-1 therapy, 2.9%—or 10 patients—developed neurological complications, including necrotizing myopathy, various neuropathies, cerebellar ataxia, internuclear ophthalmoplegia, retinopathy, and headache, researchers reported. The time to maximum symptom severity ranged from just 1 day to 3 months or more.

In all patients, anti-PD-1 therapy was stopped, and patients were treated with corticosteroids, intravenous immunoglobulin, and in 1 case plasma exchange. While 9 patients improved, 1 patient with severe necrotizing myopathy died, according to the study.

“Although neurological complications relating to anti-PD-1 antibody therapy appear to be rare, we will likely encounter more cases in the future,” researchers wrote, “as the use of these medications in the treatment of metastatic cancer continues to expand.”

—Jolynn Tumolo

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