Detect it so you can treat it: A case series and proposed checklist to detect neurotoxicity in checkpoint therapy

Abstract

Background Checkpoint inhibitors show impressive and durable responses in various cancer types and provide new avenues for cancer immunotherapy. However, these drugs have a variety of adverse events. Common autoimmune-related adverse effects include fatigue, hepatitis, skin rash, endocrine deficiencies, and colitis. Neurotoxicity has been reported, but its incidence and course remain unclear. Methods To illustrate the broad spectrum of neurotoxicity, we exemplarily report the neurological adverse events of five patients with melanoma and one patient with differentiated thyroid cancer who received checkpoint inhibitors at Essen University Hospital (Essen, Germany). Results After treatment with ipilimumab, nivolumab or pembrolizumab, neurotoxic effects included hypophysitis-associated neck pain and headache, Guillain-Barré syndrome, transverse myelitis, acute brachial plexus neuritis, and ocular myasthenia gravis. Conclusions Checkpoint inhibitor therapy remains a success story; however, neurological immune-related adverse events may cause severe life-threatening conditions. We propose a guide for the early detection of neurological adverse events during routine clinical treatment to prevent more severe courses of checkpoint inhibitor-induced neurotoxicity.

Association Between Clinical Factors and Result of Immune Checkpoint Inhibitor Related Myasthenia Gravis: A Single Center Experience and Systematic Review

“…ICI-related neurological adverse events are relatively infrequent; however, pooled analyses have shown that they are associated with increased morbidity and mortality ( 3 – 5 ). Myasthenia gravis (MG) is an autoimmune disorder mediated by autoantibodies, including anti-acetylcholine receptor (AChR) or anti-muscle associated receptor tyrosine kinase (MUSK) antibodies that target the neuromuscular junction ( 6 ).…”

Hypothyroidism as an immune-related adverse event caused by atezolizumab in a patient with muscle spasms: a case report

“…Myositis due to irAEs has also been reported, especially myocarditis, which is known to have a high fatality rate [ 14 ]. In addition, some reports have described Guillain-Barre syndrome or myasthenia gravis developing as an irAE due to ICIs, and these diagnoses need to be ruled out when symptoms of muscle weakness are present [ 15 ]. In the present case, muscle cramps and grasping pain were observed, but no symptoms such as muscle weakness, decreased swallowing function, or dyspnea were apparent, so Guillain-Barre syndrome and myasthenia gravis were not suspected.…”

Evaluation and management of acute high-grade immunotherapy-related neurotoxicity

“…The resulting nerve damage causes varying degrees of weakness, sensory loss, and autonomic dysfunction. Checkpoint inhibitors have been associated with acute transverse myelitis in case reports and series [ 73 , 107 , 117 , [124] , [125] , [126] , [127] , [128] , [129] ].…”

“…Almost all patients present with rapidly progressive lower extremity paraparesis, sensory loss and sphincter dysfunction [ 130 ]. There are reports of tetraparesis [ 126 , 128 ]. Deep tendon reflexes may be affected, and Babinski sign may be present [ 124 ].…”