title: Anti-programmed cell death-1 therapy and insulin-dependent diabetes: a case report.
abstract: The anti programmed cell death-1 (PD-1) antibodies pembrolizumab and nivolumab have been recently licensed by the Food and Drug Administration for the treatment of advanced melanoma. Immune checkpoint inhibitors such as these can induce endocrine adverse events but autoimmune diabetes has not been described to date. However, there is a strong preclinical rationale that supports this autoimmune toxicity. We describe for the first time the case of an adult patient who developed autoimmune diabetes likely as a consequence of PD-1 inhibition with pembrolizumab. The presence of high serum titres of anti-glutamic acid decarboxylase antibodies together with a suggestive clinical presentation, age of the patient and preclinical data strongly support an autoimmune aetiology of the diabetes. Moreover, the patient was found to have a well-known high-risk human leucocyte antigen type for the development of type 1 diabetes in children, so the PD-1 inhibition is very likely to have triggered the autoimmune phenomenon. Our case suggests that insulin-dependent diabetes might be a rare but important anti-PD-1 immune-related adverse event.
authors.affiliation: Renal and Melanoma Unit, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK.
authors.forename: Juan
authors.initials: J
authors.lastname: Martin-Liberal
authors.forename: Andrew Js
authors.initials: AJ
authors.lastname: Furness
authors.forename: Kroopa
authors.initials: K
authors.lastname: Joshi
authors.forename: Karl S
authors.initials: KS
authors.lastname: Peggs
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Quezada
authors.forename: James
authors.initials: J
authors.lastname: Larkin
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced* / Q000276:immunology; D005260:Female; D006801:Humans; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab
references.citation: N Engl J Med. 2012 Jun 28;366(26):2455-65
references.pmid: 22658128
references.citation: J Exp Med. 2003 Jul 7;198(1):63-9
references.pmid: 12847137
references.citation: Clin Immunol. 2007 Oct;125(1):16-25
references.pmid: 17627890
references.citation: PLoS One. 2014 Feb 28;9(2):e89561
references.pmid: 24586872
references.citation: J Clin Endocrinol Metab. 2004 Aug;89(8):3896-902
references.pmid: 15292324