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Journal of Skin Cancer
Volume 2018, Article ID 9602540, 13 pages
Research Article

Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical Management

1Chris O’Brien Lifehouse, Camperdown, NSW, Australia
2Concord Repatriation General Hospital, Sydney, NSW, Australia
3Centenary Institute, Sydney, NSW, Australia
4Sydney Medical School, University of Sydney, Camperdown, NSW, Australia
5Royal Prince Alfred Hospital, Camperdown, NSW, Australia

Correspondence should be addressed to Anna J. Lomax; ua.gro.hl@xamol.anna

Received 15 August 2017; Revised 31 October 2017; Accepted 6 November 2017; Published 21 January 2018

Academic Editor: Arash Kimyai-Asadi

Copyright © 2018 Anna J. Lomax et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Immune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4 antibodies) are a standard of care for advanced melanoma. Novel toxicities comprise immune-related adverse events (irAE). With increasing use, irAE require recognition, practical management strategies, and multidisciplinary care. We retrospectively evaluated the incidence, kinetics, and management of irAE in 41 patients receiving anti-PD-1 antibody therapy (pembrolizumab) for advanced melanoma. 63% received prior anti-CTLA-4 antibody therapy (ipilimumab). IrAE occurred in 54%, most commonly dermatological (24%), rheumatological (22%), and thyroid dysfunction (12%). Thyroiditis was characterised by a brief asymptomatic hyperthyroid phase followed by a symptomatic hypothyroid phase requiring thyroxine replacement. Transplant rejection doses of methylprednisolone were necessary to manage refractory hepatotoxicity. A bullous pemphigoid-like skin reaction with refractory pruritus responded to corticosteroids and neuropathic analgesia. Disabling grade 3-4 oligoarthritis required sulfasalazine therapy in combination with steroids. The median interval between the last dose of anti-CTLA-4 antibody and the first dose of anti-PD-1 therapy was 2.0 months (range: 0.4 to 22.4). Toxicities may occur late; this requires vigilance and multidisciplinary management which may allow effective anticancer therapy to continue. Management algorithms for thyroiditis, hypophysitis, arthralgia/arthritis, colitis, steroid-refractory hepatitis, and skin toxicity are discussed.