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Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes

Kotwal, Anupam ; Haddox, Candace ; Block, Matthew ; Kudva, Yogish C

BMJ open diabetes research & care, 2019-02, Vol.7 (1), p.e000591-e000591 [Periódico revisado por pares]

England: BMJ Publishing Group LTD

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Título:
Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes
Autor: Kotwal, Anupam ; Haddox, Candace ; Block, Matthew ; Kudva, Yogish C
Assuntos: Antibodies, Monoclonal, Humanized - adverse effects ; Antigens ; Apoptosis ; Cancer ; Clinical Care/Education/Nutrition ; Clinical trials ; CTLA-4 Antigen - therapeutic use ; Cytotoxicity ; Diabetes ; Diabetes Mellitus, Type 1 - chemically induced ; Diabetes Mellitus, Type 1 - epidemiology ; Diabetes Mellitus, Type 1 - metabolism ; Diabetes Mellitus, Type 2 - epidemiology ; Diabetes Mellitus, Type 2 - metabolism ; Female ; Glycated Hemoglobin A - metabolism ; Hemoglobin ; Humans ; Immunity, Cellular - drug effects ; Immunotherapy ; Insulin ; Ligands ; Lymphocytes ; Male ; Melanoma ; Metastasis ; Middle Aged ; Monoclonal antibodies ; Nivolumab - adverse effects ; Programmed Cell Death 1 Receptor - therapeutic use ; Proteins ; Retrospective Studies ; Systematic review ; T cell receptors ; Targeted cancer therapy ; Thyroid gland
É parte de: BMJ open diabetes research & care, 2019-02, Vol.7 (1), p.e000591-e000591
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: ObjectiveInsulin-dependent diabetes can occur with immune checkpoint inhibitor (ICI) therapy. We aimed to characterize the frequency, natural history and potential predictors of ICI-induced diabetes.Research design and methodsWe reviewed 1444 patients treated with ICIs over 6 years at our cancer center, and from the 1163 patients who received programmed cell death protein 1 (PD-1) inhibitors, we identified 21 such cases, 12 of which developed new-onset insulin-dependent diabetes and 9 experienced worsening of pre-existing type 2 diabetes.ResultsICI-induced diabetes occurred most frequently with pembrolizumab (2.2%) compared with nivolumab (1%) and ipilimumab (0%). The median age was 61 years, and body mass index was 31 kg/m2, which are both higher than expected for spontaneous type 1 diabetes. Other immune-related adverse events occurred in 62%, the most common being immune mediated thyroid disease. New-onset insulin-dependent diabetes developed after a median of four cycles or 5 months; 67% presented with diabetic ketoacidosis and 83% with low or undetectable C-peptide. Autoantibodies were elevated in 5/7 (71%) at the time of new-onset diabetes. Diabetes did not resolve during a median follow-up of 1 year.ConclusionsPD-1 inhibitors can lead to insulin deficiency presenting as new-onset diabetes or worsening of pre-existing type 2 diabetes, with a frequency of 1.8 %. The underlying mechanism appears similar to spontaneous type 1 diabetes but there is a faster progression to severe insulin deficiency. Better characterization of ICI-induced diabetes will improve patient care and enhance our understanding of immune-mediated diabetes.
Editor: England: BMJ Publishing Group LTD
Idioma: Inglês

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Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes

Kotwal, Anupam ; Haddox, Candace ; Block, Matthew ; Kudva, Yogish C

England: BMJ Publishing Group LTD

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