Atypical Neurological Complications of Ipilimumab Therapy in Patients With Metastatic Melanoma

Neuro Oncol. 2014 Apr;16(4):589-93. doi: 10.1093/neuonc/nou001. Epub 2014 Jan 30.

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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects*
  • Brain Neoplasms / complications*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / secondary
  • Female
  • Humans
  • Ipilimumab
  • Liver Neoplasms / complications*
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / secondary
  • Male
  • Melanoma / complications*
  • Melanoma / drug therapy
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Staging
  • Nervous System Diseases / chemically induced*
  • Nervous System Diseases / pathology
  • Prognosis

Substances

  • Antibodies, Monoclonal
  • Ipilimumab