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Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors

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 sol...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054443/
https://www.ncbi.nlm.nih.gov/pubmed/29937434
http://dx.doi.org/10.2337/dbi18-0002
Descripción
Sumario: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.