Serious adverse effect of Keytruda in two patients.

Researchers reported two cases of demyelinating polyradiculoneuropathy after treatment with pembrolizumab (Keytruda) for advanced melanoma.

The report, in a letter published Wednesday in the New England Journal of Medicine, raises concerns about serious, perhaps irreversible, and previously unknown adverse effects from this class of drug, which targets the PD-1 immune checkpoint pathway. These immunotherapies, offering a whole new way of attacking cancer, have generated excitement across the oncology community in recent years.

The first patient was receiving treatment for recurrent nasal-cavity melanoma, and developed symptoms consistent with Guillain-Barré syndrome 8 weeks after beginning pembrolizumab therapy (2 mg/kg every 3 weeks), according to Philippe Saiag, MD, PhD, of Versailles Saint-Quentin-en-Yvelines University in Versailles, France, and colleagues.

The second patient was undergoing treatment for metastatic melanoma, and developed chronic inflammatory demyelinating polyradiculoneuropathy 20 weeks after beginning pembrolizumab therapy (2 mg/kg every 3 weeks). The patient also received ipilimumab (Yervoy) and binimetinib, they wrote.

The first patient presented with several symptoms including paresthesia and hypoesthesia of all limbs before the third infusion of pembrolizumab; the second patient also had multiple symptoms, including paresthesias of the arms and neck pain, between the sixth and seventh infusions.

In both cases, pembrolizumab was discontinued. The first patient responded to treatment in that her neurologic symptoms reached a peak within 3 weeks and decreased over the next 2 months. However, in the second patient, treatement did not lead to improvement in neurologic symptoms over 13 months of follow-up, the authors reported.

“We conclude that the two conditions may be associated with pembrolizumab, since neither patient had evidence of infectious causes or a documented paraneoplastic syndrome,” they wrote.

They explained that since, “demyelinating polyradiculoneuropathies are believed to be a result of autoimmunization, we speculate that PD-1–blocking antibodies may trigger one or more of the complex immune mechanisms involved in this disease.”