Clinical spectrum of neuromuscular complications after immune checkpoint inhibition

Abstract

Cancer immunotherapy has transformed the field of oncology and enabled more effective management of previously refractory neoplasms by activation of the immune response. Upregulation of the immune response may also trigger autoimmune adverse events, including neuromuscular complications. We performed a systematic review of autoimmune neuromuscular complications following immune checkpoint blockade. We searched PubMed database and identified 81 cases described, including 30 cases of myasthenia gravis (MG), 29 cases of neuropathy and 22 cases of myopathy. Most patients (89%) developed neuromuscular complications within 3 months from starting immune checkpoint blockade and 40% of all patients had elevated serum CK>1000 IU/L (typical normal <200). Guillain-Barre syndrome variants and overlaps of MG with myositis and/or myocarditis also occurred. One quarter of myasthenia patients presented with exacerbations of previously diagnosed myasthenia gravis, while neuropathy and myopathy typically presented with a new onset. Most patients improved with immunomodulatory treatment, but neuromuscular complications were sometimes refractory and associated with high mortality of 26% from cancer recurrence, comorbidities, or treatment complications. Poor outcomes were more common with exacerbations of pre-existing myasthenia gravis and myocarditis overlap. Future prospective studies are needed to elucidate mechanisms and risk factors for autoimmune adverse events following immune checkpoint blockade.

Keywords: Immune checkpoint inhibitors; Myasthenia gravis; Myopathy; Neuromuscular; Neuropathy.