Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma

Ipilimumab is a novel FDA-approved recombinant human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 and has been used to treat patients with metastatic melanoma. Immune-related neurological adverse effects include inflammatory myopathy, aseptic meningitis, posterior reversible encephalopathy syndrome, Guillain-Barré syndrome, myasthenia gravis–type syndrome, sensorimotor neuropathy, and inflammatory enteric neuropathy. To date, there is no report for ipilimumab-induced chronic inflammatory demyelinating polyneuropathy (CIDP), transverse myelitis (TM), or concurrent myositis and myasthenia gravis–type syndrome. Our objective is to raise early recognition of atypical neurological adverse events and to share our therapeutic approach. We report 3 cases of metastatic melanoma treated with ipilimumab in which the patients developed CIDP, TM, and concurrent myositis and myasthenia gravis–type syndrome, respectively, at the MD Anderson Cancer Center between July 2012 and June 2013. Patients consented to release of medical information for publication/educational purposes. Our 3 cases of metastatic melanoma treated with ipilimumab developed CIDP, TM, and concurrent myositis and myasthenia gravis–type syndrome, respectively. The median time to onset of immune-related adverse events following ipilimumab treatment ranged from 1 to 2 weeks. Ipilimumab was discontinued due to the severe neurological symptoms. Plasmapheresis was initiated in the patients with CIDP and concurrent myositis and myasthenia gravis–type syndrome; high-dose intravenous steroids were given to the patient with TM, and significant clinical response was demonstrated. Ipilimumab could induce a wide spectrum of neurological adverse effects. Our findings support the standard treatment of withholding or discontinuing ipilimumab. Plasmapheresis or high-dose intravenous steroids may be considered as the initial choice of treatment for severe ipilimumab-related neurological adverse events. Improvement of neurological symptoms may be seen within 2 weeks.