Vogt-Koyanagi-Harada-like Syndrome After CTLA-4 Inhibition With Ipilimumab for Metastatic Melanoma

• Type of Material: Article
• Authors: Jason N. Crosson, Emory University; Philip Laird, Emory University; Matthew Debiec, Emory University; Chris Bergstrom, Emory University; David Lawson, Emory University; Steven Yeh, Emory University
• Language: English
• Date: 2015-02-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Wolters Kluwer Health, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1097/CJI.0000000000000066
• Title of Journal or Parent Work: Journal of Immunotherapy
• ISSN: 1524-9557
• Volume: 38
• Issue: 2
• Start Page: 80
• End Page: 84
• Grant/Funding Information: This work was supported in part by an unrestricted departmental grant from Research to Prevent Blindness (New York, NY) to the Emory Eye Center and an NEI Core Grant for Vision Research (P30 EY 006360).
• Keywords: IMMUNOTHERAPY; Immunology; Life Sciences & Biomedicine; ANTIGEN-4; Medicine, Research & Experimental; Research & Experimental Medicine; CANCER; autoimmunity; immunotherapy; CTLA-4 antibody; DISEASE; ipilimumab; Oncology; Science & Technology; AUTOIMMUNITY; uveitis; melanoma
• Research Categories: Health Sciences, Oncology; Health Sciences, Immunology; Health Sciences, Opthamology

Abstract

Cytotoxic T-lymphocyte-associated antigen is a naturally occurring inhibitor of T-cell costimulation. Monoclonal antibody inhibition of cytotoxic T-lymphocyte-associated antigen with ipilimumab blocks this negative regulator of costimulation, promoting T-cell activation and survival, and leads to melanoma regression. Findings of the Vogt-Koyanagi-Harada (VKH) syndrome, an uveomeningitic syndrome that features neurological, auditory, ophthalmologic, and cutaneous involvement because of autoimmune targeting of melanocytic antigen, have rarely been described in association with melanoma immunotherapy. We describe a case of VKH-like syndrome in a 45-year-old HLA-A02-positive patient with metastatic melanoma treated with ipilimumab. Disruption of immune tolerance by ipilimumab led to melanoma remission while also inciting systemic and ophthalmic autoimmunity toward melanocytic antigen. These observations provide insight into the pathophysiology of the VKH syndrome, and the balance between tumor-associated tolerance and autoimmunity.