From the Guidelines
Pembrolizumab can cause neuropathy as a side effect, with an estimated incidence of around 6.8% of patients, as reported in the most recent study 1. Pembrolizumab (brand name Keytruda) is an immune checkpoint inhibitor that works by enhancing T-cell immune responses against cancer cells. Peripheral neuropathy associated with pembrolizumab typically presents as numbness, tingling, or pain in the hands and feet. This neurological adverse effect occurs because the activated immune system may occasionally target peripheral nerves, leading to inflammation and nerve damage. If a patient on pembrolizumab develops new or worsening neuropathic symptoms, they should report these to their healthcare provider immediately. Management may include dose interruption, symptomatic treatment with medications like gabapentin or pregabalin, and in severe cases, corticosteroids to reduce immune-mediated inflammation. Most cases of pembrolizumab-induced neuropathy are mild to moderate in severity and may improve with appropriate management, as supported by recent studies 1. It is essential to note that the incidence of neuropathy with pembrolizumab can vary depending on the specific treatment regimen and patient population, as highlighted in a recent review of immunotherapy combinations with chemotherapy 1. However, based on the most recent and highest-quality evidence, pembrolizumab-induced neuropathy is a recognized side effect that requires prompt attention and management to minimize its impact on patient quality of life.
From the FDA Drug Label
Peripheral neuropathy‡584.2576
- Chemotherapy (paclitaxel and cisplatin or paclitaxel and carboplatin) † Graded per NCI CTCAE v4. 0 ‡ Includes neuropathy peripheral, peripheral sensory neuropathy, peripheral motor neuropathy, peripheral sensorimotor neuropathy, paresthesia
Yes, Pembrolizumab can cause neuropathy. The incidence of peripheral neuropathy was 58% in patients receiving KEYTRUDA in combination with chemotherapy with or without bevacizumab 2.
From the Research
Pembrolizumab and Neuropathy
- Pembrolizumab, an anti-PD1 agent, has been linked to an increased risk of various neurological immune-related adverse events (irAEs), including neuropathy 3, 4, 5.
- There have been reports of pembrolizumab-induced peripheral neuropathy, with symptoms such as facial paresis, ptosis, ophthalmoplegia, and dysphonia 3, as well as Guillain-Barré syndrome-like onset 4.
- A case study described a patient who developed pembrolizumab-induced peripheral nervous system damage, characterized by a combination of myositis/myasthenia overlap syndrome and motor axonal polyneuropathy 5.
- Neurological irAEs, including neuropathy, are a rare complication of immune checkpoint inhibitors like pembrolizumab, but can lead to long-term morbidity 6.
- Treatment for pembrolizumab-induced neuropathy often involves discontinuation of the drug and administration of high-dose corticosteroids or intravenous immunoglobulin (IVIg) 3, 4, 5.
Characteristics of Pembrolizumab-Induced Neuropathy
- Pembrolizumab-induced neuropathy can manifest as isolated cranial neuropathy or peripheral neuropathy 3, 4.
- Symptoms can include facial weakness, ptosis, ophthalmoplegia, dysphonia, and limb weakness 3, 4, 5.
- Nerve conduction studies and electromyography can help diagnose neuropathy and exclude other conditions 3, 5.
- Treatment response can vary, but early recognition and intervention are crucial to prevent long-term damage 3, 4, 5.
Comparison with Other Conditions
- Pembrolizumab-induced neuropathy is distinct from other forms of neuropathy, such as those caused by spinal cord injury or other medications 7.
- The pathophysiology and clinical presentation of pembrolizumab-induced neuropathy are unique and require specific consideration in diagnosis and treatment 3, 4, 5, 6.