Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: chronic inflammatory demyelinating polyneuropathy; immune-related adverse events; ipilimumab; metastatic melanoma; transverse myelitis.

Fig. 1.

Case 2, A–C Magnetic resonance imaging of the thoracic spine without contrast shows a focal T2 signal abnormality at the T9-10 and T10 levels within the cord. These are confirmed on the axial T2-weighted images. These appear very focal, with no expansion of the cord. Case 3, D Videofluoroscopy shows a very prominent cricopharyngeus muscle at the C5-6 level, which prevents the passage of contrast and is thought to represent the patient's cause of dysphagia.