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Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors

2018; American Diabetes Association; Volume: 67; Issue: 8 Linguagem: Inglês

10.2337/dbi18-0002

1939-327X

Angeliki M. Stamatouli, Zoe Quandt, Ana Luisa Perdigoto, Pamela Clark, Harriet M. Kluger, Sarah A. Weiss, Scott Gettinger, Mario Sznol, Arabella Young, Robert J Rushakoff, James Lee, Jeffrey A. Bluestone, Mark S. Anderson, Kevan C. Herold,

Metabolism, Diabetes, and Cancer

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.