Neurologic Immune-Related Adverse Events Following Immune Checkpoint Inhibitor Therapy for Cancer

Immune checkpoint inhibitor therapy (ICI) targets T-cell regulatory pathways to enhance antitumor responses. Despite successes with ICI for various cancers, case reports of neurologic immune-related adverse events (nirAEs) prompted two studies to further understanding of these events.

Kao and colleagues retrospectively studied 347 patients treated at one tertiary center during a 20-month period with either nivolumab or pembrolizumab for melanoma or other cancers. Ten patients (2.9%) developed nirAEs. Maximum symptom severity was variable and occurred 1 day to 3 months after ICI started. The most common nirAEs were neuromuscular, including myopathy (N=2) and neuropathy (N=4); single cases of cerebellar ataxia, autoimmune retinopathy, bilateral ophthalmoplegia, and headache occurred. ICI was discontinued for 7 of the 10 patients. One patient spontaneously improved, nine improved with immunosuppressive treatment (corticosteroids, intravenous immunoglobulin, and/or plasmapheresis), and one patient died. Of the nine survivors, three had subsequent cancer progression and died, two remained in complete remission, and four were stable. ICI was resumed for four patients, one of whom required maintenance immunosuppression.

Suzuki and colleagues reviewed 2-year safety data from postmarketing surveys in Japan to report clinical features of myasthenia gravis (MG) following ICI. The researchers studied 10,277 patients with cancer (mainly melanoma and non–small-cell lung cancer) treated with nivolumab (N=9869) or ipilimumab (N=408), compared with 105 patients with idiopathic MG. No patient had thymoma. Of the nivolumab-treated patients, 12 (0.12%) developed MG (nivoMG) within 16 weeks of their first nivolumab infusion. No ipilimumab-treated patients developed myasthenia. Frequencies of ocular, limb, and neck muscle weakness did not differ relative to idiopathic MG patients. Six progressed to myasthenic crisis. Of the 12 nivoMG patients, 10 were anti-AChR antibody seropositive and 2 were seronegative, including for anti-MUSK antibodies. Four were diagnosed with myositis, three with myocarditis, and one with both. Nivolumab was ceased and immunosuppressive treatment initiated for all patients. Postintervention, two had minimal myasthenia, five improved, one was unchanged, and two died. Tumor reduction was seen in four patients with nivoMG, and nivolumab was resumed in two patients without myasthenia relapse.