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.
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Abbreviations
- Anti-GAD:
-
Anti-glutamic acid decarboxylase
- FDA:
-
Food and Drug Administration
- HLA:
-
Human leucocyte antigen
- LADA:
-
Latent autoimmune diabetes of the adult
- PD-1:
-
Programmed cell death-1
References
Ansari MJ, Salama AD, Chitnis T, Smith RN, Yagita H, Akiba H et al (2003) The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med 198(1):63–69
Guleria I, Gubbels Bupp M, Dada S, Fife B, Tang Q, Ansari MJ et al (2007) Mechanisms of PDL1-mediated regulation of autoimmune diabetes. Clin Immunol 125(1):16–25
Kochupurakkal NM, Kruger AJ, Tripathi S, Zhu B, Adams LT, Rainbow DB et al (2014) Blockade of the programmed death-1 (PD1) pathway undermines potent genetic protection from type 1 diabetes. PLoS One 9(2):e89561
Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366(26):2455–2465
Barker JM, Barriga KJ, Yu L, Miao D, Erlich HA, Norris JM et al (2004) Prediction of autoantibody positivity and progression to type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY). J Clin Endocrinol Metab 89(8):3896–3902
Conflict of interest
James Larkin has received research funding from Pfizer and Novartis. He has also been a consultant for GlaxoSmithKline, Bristol-Myers Squib, Pfizer and Novartis. The rest of the authors have no conflict of interest to disclose.
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Martin-Liberal, J., Furness, A.J., Joshi, K. et al. Anti-programmed cell death-1 therapy and insulin-dependent diabetes: a case report. Cancer Immunol Immunother 64, 765–767 (2015). https://doi.org/10.1007/s00262-015-1689-1
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DOI: https://doi.org/10.1007/s00262-015-1689-1