Neuromuscular complications of immune checkpoint inhibitor therapy

Abstract

Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however, the unbridling of the immune system may induce a variety of immune-related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI-related immune diseases. Accordingly, while the optimal treatment for ICPI-related neuromuscular disorders generally follows a traditional paradigm, there are important novel considerations in selecting appropriate immunosuppressive therapy. This review presents 2 new cases, a summary of neuromuscular ICPI complications, and an approach to the diagnosis and treatment of these disorders. Muscle Nerve, 2018.

Nivolumab‐induced neuralgic amyotrophy with hourglass‐like constriction of the anterior interosseous nerve

“…One of these patients also received nivolumab, with the first dose having been given 6 weeks prior to symptom onset. Otherwise, nivolumab is most associated with an irAE consistent with acute inflammatory demyelinating polyneuropathy (AIDP) . Our patient did not develop diffuse areflexia or large‐fiber electrodiagnostic abnormalities and lacked demyelinating features, making AIDP unlikely.…”

“…Although neuromuscular irAEs due to ICPIs are not uncommon, mononeuropathy or plexopathy appear rare; 2 of 51 cases described by Kolb et al 2 involved single nerves (oculomotor nerve in 1 and facial and abducens nerves in the other). One of these patients also received nivolumab, with the first dose having been given 6 weeks prior to symptom onset.…”

“…Identification of potential neurological complications early in the course of ICPIs can prompt cessation of the ICPIs and consideration of steroids. 4 Although Kolb et al 2 included rare cranial mononeuropathies in their supplemental data, 2 there were no reported instances of NA, and additional literature searches for ICPI and NA (including synonyms Parsonage-Turner or brachial plexitis) returned no results. Our clinical experience in this case, supported by the ultrasonographic findings, suggests that neuralgic amyotrophy should be included as an ICPI-mediated irAE.…”

“…Although spinal muscular atrophy (SMA) is a primary motor neuron disorder, autonomic system dysfunction has been increasingly observed. 1,2 Parents of children with SMA describe a variety of symptoms, such as excessive sweating, bradycardia, and distal necrosis, generally only in patients with type 1 SMA (SMA1), suggesting autonomic dysfunction as an integral part of the SMA phenotype. [3][4][5] Vascular perfusion abnormalities have been reported in a few infants with severe SMA1.…”

Trouble at the junction: When myopathy and myasthenia overlap

“…Since the introduction of immune checkpoint inhibitors (ICI) in cancer immunotherapy, several cases of myasthenia gravis and immune‐mediated myopathies in ICI‐treated patients have been reported . ICI‐induced neuromuscular complications have emerged as rare but serious adverse effects of these medications and generally develop within 3 months of initiating therapy .…”