XML Template (2015) [10.2.2015–5:11pm] [1–7] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/OPPJ/Vol00000/150010/APPFile/SG-OPPJ150010.3d (OPP) [INVALID Stage] Case Report Ipilimumab-induced necrotic myelopathy in a patient with metastatic melanoma: A case report and review of literature Al-Ola Abdallah 1 , Aline Herlopian 2 , Rahul Ravilla 3 , Meghana Bansal 1 , Sowmya Chandra-Reddy 3 , Fade Mahmoud 1 , Shirley Ong 2 , Murat Gokden 4 and Laura Hutchins 1 Abstract Ipilimumab is a novel humanized monoclonal antibody directed against cytotoxic T lymphocyte antigen 4, a T-cell surface molecule involved in down-regulation and suppression of the T cell response to stimuli. Patients treated with ipilimumab are at risk for immune-related adverse events involving the skin, digestive tract, liver and endocrine organs. Few case reports of immune-related adverse effects involving central or peripheral nervous system due to ipilimumab are pub- lished. These include inflammatory myopathy, aseptic meningitis, severe meningo-radiculo-neuritis, temporal arteritis, Guillain-Barre syndrome, and posterior reversible encephalopathy syndrome. We report the first case of ipilimumab- induced progressive necrotic myelopathy. Keywords Ipilimumab, progressive necrotic myelopathy, immune-related adverse events Introduction Cytotoxic T lymphocyte antigen 4 (CTLA-4) receptor causes immune system down-regulation by competing with the co-stimulatory molecule CD28 for their common ligands CD80 and CD86. 1,2 Ipilimumab, a recombinant human monoclonal antibody against CTLA-4 receptor, is FDA-approved after it showed an overall survival benefit in the first line setting for patients with metastatic melanoma. 3,4 By binding to CTLA-4 receptor, ipilimumab releases the inhibition and up-regulates the immune system. Patients treated with ipilimumab are at risk for immune-related adverse events (irAE) of the skin, digestive tract, liver, nervous system and endocrine organs. 5 The incidence of neurologic irAE due to ipilimumab in clinical trials is 0.1%. 6 These include inflammatory myopathy, aseptic meningitis, severe meningo-radi- culo-neuritis, temporal arteritis, Guillain-Barre syn- drome, and posterior reversible encephalopathy syndrome. 7–12 We report the first case of ipilimu- mab-induced necrotizing myelopathy. Case report A 45-year-old woman underwent wide local excision for a biopsy-proven cutaneous melanoma stage IA (T 1a , N 0 , M 0 ) over her left shoulder in 2008. In January 2014, she presented with headache, vertigo, nausea, vomiting, and gait ataxia. MRI of the brain with contrast revealed a 3 cm enhancing right 1 Department of Internal Medicine, Division of Hematology and Oncology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA 2 Department of Internal Medicine, Division of Neurology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA 3 Department of Internal Medicine, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA 4 Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA Corresponding author: Laura Hutchins, Department of Internal Medicine, Division of Hematology and Oncology, University of Arkansas for Medical Sciences (UAMS), 4301, West Markham St., Little Rock, AR 72205, USA. Email: HutchinsLauraF@uams.edu J Oncol Pharm Practice 0(0) 1–6 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1078155215572932 opp.sagepub.com