Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors

Author:

Stamatouli Angeliki M.1,Quandt Zoe2,Perdigoto Ana Luisa1,Clark Pamela L.3,Kluger Harriet4,Weiss Sarah A.4,Gettinger Scott4,Sznol Mario4,Young Arabella2,Rushakoff Robert2,Lee James5,Bluestone Jeffrey A.26,Anderson Mark2,Herold Kevan C.13ORCID

Affiliation:

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

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.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

Leona M. and Harry B. Helmsley Charitable Trust

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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