Describe the spectrum of peripheral nervous system complications associated with immune checkpoint inhibitors (ICIs).

While ICIs have revolutionized the treatment of previously incurable malignancies, their use has been associated with a variety of devastating autoimmune complications. ICIs commonly cause toxicities affecting the peripheral nervous system but the range of such complications has yet to be defined.

We performed a single-center retrospective review of patients diagnosed with peripheral nervous system complications of ICIs since 2013. Basic epidemiologic and laboratory data were collected as well as electrophysiological investigations as applicable. The main outcomes were clinical manifestations and treatment regimens.  

Six patients with metastatic cancer treated with ICIs were included. The mean age was 64 (range 49-73) years. Two patients received nivolumab monotherapy, one received ipilimumab monotherapy, two were treated with nivolumab in combination with ipilimumab, and one received pembrolizumab monotherapy. Complications included myeloradiculoneuritis (1), acute inflammatory demyelinating polyradiculoneuropathy (1), myositis (2), and myasthenia gravis (3). The patient with myeloradiculoneuritis tested positive for CRMP5 IgG, while only one of the three patients with a myasthenic phenotype was positive for the acetylcholine-receptor antibody. All six patients received steroids and had checkpoint inhibitor therapy discontinued.  Two received concurrent treatment with intravenous immunoglobulin and two with plasmapheresis, while two patients were treated with both agents. One patient with severe necrotizing myopathy remains quadraparetic and ventilator-dependent, while another with a mixed picture of myasthenia and biopsy-proven dermatomyositis died of pneumonia secondary to severe neuromuscular weakness.

The phenotypic spectrum of neurologic complications associated with ICIs remains heterogeneous and the identification of further cases is necessary to further our understanding of these toxicities.