SY23-5 - Immune checkpoint inhibitors and neuromuscular adverse events

Abstract

Neuromuscular adverse events (AEs) associated with cancer treatment with immune checkpoint inhibitors (ICIs) include diverse clinical subsets. The general features of neuromuscular AEs have not been elucidated because the frequency is generally low, ranging from 1%-2% of cancer patients undergoing ICIs therapy. The diseases affect the central nervous system, peripheral nerves, neuromuscular junction, and muscle. Disease onset and progression may be rapid with a critical clinical course. The clinical presentation may be different from that of patients unrelated to drugs. Brain MRI images or laboratory findings do not always yield useful information, even if cancer patients suffer from severe neurological symptoms. Prior treatment including cytotoxic chemotherapies and radiation may have been factors in causing neuromuscular damage. Metastatic lesions potentially produce new neurological symptoms. In addition, paraneoplastic syndrome, a remote effect of malignancy on neuromuscular organs, is always considered as a differential diagnosis. Stroke and epilepsy are serious events requiring the permanent termination of ICIs treatment. Headache, dizziness, and dysgeusia were relatively common and mild treatment-related AEs. In contrast, representative immune-related AEs such as autoimmune encephalitis, demyelinating polyneuropathy, myasthenia, and myositis were serious. There was a tight association between myasthenia, myositis, and myocarditis. There are guidelines for the treatment of neuromuscular immune-mediated AEs. For all but the minimum neurological symptoms, checkpoint inhibitor therapy should be withheld until the nature of the AEs is identified. Immune-modulating medication is generally effective for neuromuscular AEs. Both CD8+ cytotoxic T-cells and autoantibodies are involved in the pathogenesis of neuromuscular AEs. Correct understanding of neuromuscular AEs is required for the best management of cancer patients.