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Open Access Publications from the University of California

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

  • Author(s): Stamatouli, Angeliki M
  • Quandt, Zoe
  • Perdigoto, Ana Luisa
  • Clark, Pamela L
  • Kluger, Harriet
  • Weiss, Sarah A
  • Gettinger, Scott
  • Sznol, Mario
  • Young, Arabella
  • Rushakoff, Robert
  • Lee, James
  • Bluestone, Jeffrey A
  • Anderson, Mark
  • Herold, Kevan C
  • et al.

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.

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