Cases: Neurological complications linked to anti-PD-1 immunotherapies

Clinical Brief – September 12th

The Brief

Last week, researchers at the Mayo Clinic published a report on how they managed 10 patients who experienced immune-mediated neurological side effects after treatments with nivolumab (Opdivo) or pembrolizumab (Keytruda).

Reports like these teach us more about the possible harms of immunotherapies and balances the studies that are designed to show their efficacies.

What are anti-PD-1 immunotherapies?

Anti-PD-1 immunotherapies make up a class of cancer treatments designed to tweak the immune system to attack cancers. Nivolumab and pembrolizumab are two such immunotherapies. Others targeting the same pathway include atezolizumab (Tecentriq), avelumab (Bavencio), and durvalumab (Imfinzi).

For some, immunotherapies can mean complete remission and prolonged survival. For others, debilitating side effects may materialize. A recent STAT News report nicely demonstrated the difficult choices facing patients and their clinicians when it comes to treatment choice.

What are immune-mediated side effects?

Immune-mediated side effects are generally the result of the immune system attacking healthy tissue. This may happen in any part of the body, and I haven’t seen a reliable method to predict who and how these side effects may manifest.

These side effects are fundamentally different than those caused by chemo or targeted therapies. We’ve spent decades learning about and dealing with chemo-related side effects. And as more patients are being treated with immunotherapies over time, we are slowly learning about what to expect and how to manage some of their associated side effects as well.

The Mayo Clinic report

Researchers looked at the records of nearly 350 patients treated with nivolumab or pembrolizumab for a wide range of cancers. Ten patients experienced neurological side effects – roughly 1 in 35.

Half of these patients were being treated for metastatic melanoma. The others were getting treatment for metastatic lung cancer, mesothelioma, cancer of the esophagus, and a type of soft tissue sarcoma.

Three patients were on nivolumab, and seven were on pembrolizumab.

Neurological side effects they experienced were diverse. Three patients had symptoms of nerve damage (neuropathy and radiculopathy); three had symptoms that affected their muscles (myopathy and ophthalmoplegia); one had symptoms that affected vision (retinopathy); one had symptoms that affected speech and movement (ataxia and dysarthria); one experienced headache; and one developed a variant of the rare neurological disorder known as Guillain-Barré syndrome, or GBS.

The time to maximum symptom severity ranged from 1 day to over 3 months.

Five patients also experienced other immune-related side effects, including hypothyroidism, colitis, and hepatitis.

Treatment with nivolumab or pembrolizumab was stopped in all patients. Side effects were managed with corticosteroids in seven patients, IVIG (or IV immunoglobulin) in 3 patients, and plasma exchange in one patient.

Nine patients improved, but one patient with severe necrotizing myopathy (muscle tissue dying) didn’t make it.

Bottom line

Immunotherapies are important treatments that we can consider for patients with cancer. For a select group of patients, they can save lives. For many others, they bring new classes of side effects that patients and their caregivers need to learn to monitor themselves for, and for clinicians to learn to deal with.

Reports like this highlight these risks and help us learn from other people’s experiences.

Personally, I think it also balances out the conversation because well-controlled studies with large cohorts of patients often are designed to only highlight the potential benefits of treatment, not its potential harms.

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