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Diabetes. 2018 Aug;67(8):1471-1480. doi: 10.2337/dbi18-0002. Epub 2018 Jun 24.

Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors.

Author information

1
Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University, New Haven, CT.
2
Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, San Francisco, CA.
3
Department of Immunobiology, Yale University, New Haven, CT.
4
Section of Medical Oncology, Department of Internal Medicine, Yale University, New Haven, CT.
5
Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA.
6
Parker Institute for Cancer Immunotherapy, San Francisco, CA.
7
Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University, New Haven, CT kevan.herold@yale.edu.

Abstract

Insulin-dependent diabetes may occur in patients with cancers who are treated with checkpoint inhibitors (CPIs). We reviewed cases occurring over a 6-year period at two academic institutions and identified 27 patients in whom this developed, or an incidence of 0.9%. The patients had a variety of solid-organ cancers, but all had received either anti-PD-1 or anti-PD-L1 antibodies. Diabetes presented with ketoacidosis in 59%, and 42% had evidence of pancreatitis in the peridiagnosis period. Forty percent had at least one positive autoantibody and 21% had two or more. There was a predominance of HLA-DR4, which was present in 76% of patients. Other immune adverse events were seen in 70%, and endocrine adverse events in 44%. We conclude that autoimmune, insulin-dependent diabetes occurs in close to 1% of patients treated with anti-PD-1 or -PD-L1 CPIs. This syndrome has similarities and differences compared with classic type 1 diabetes. The dominance of HLA-DR4 suggests an opportunity to identify those at highest risk of these complications and to discover insights into the mechanisms of this adverse event.

PMID:
29937434
PMCID:
PMC6054443
DOI:
10.2337/dbi18-0002
[Indexed for MEDLINE]
Free PMC Article

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