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Cancer Immunol Immunother. 2018 Aug;67(8):1197-1208. doi: 10.1007/s00262-018-2178-0. Epub 2018 May 28.

Occurrence of type 1 and type 2 diabetes in patients treated with immunotherapy (anti-PD-1 and/or anti-CTLA-4) for metastatic melanoma: a retrospective study.

Author information

1
AP-HP Dermatology Department, Saint-Louis Hospital, INSERM U976, Université Paris Diderot-Paris VII, Sorbonne Paris Cité, 1, Avenue Claude Vellefaux, 75010, Paris, France. marie-lea.gauci@hotmail.fr.
2
AP-HP Hormonology Department, Saint-Louis Hospital, Université Paris Diderot-Paris VII, Sorbonne Paris Cité, Paris, France.
3
AP-HP Dermatology Department, Saint-Louis Hospital, INSERM U976, Université Paris Diderot-Paris VII, Sorbonne Paris Cité, 1, Avenue Claude Vellefaux, 75010, Paris, France.
4
AP-HP Diabetology Department, Lariboisière Hospital, INSERM U1138; Université Paris Diderot-Paris VII, Sorbonne Paris Cité, Paris, France.
5
AP-HP Pharmacology Department, Saint-Louis Hospital, INSERM U976, Université Paris Diderot-Paris VII, Sorbonne Paris Cité, Paris, France.
6
AP-HP Pharmacogenomic Laboratory, Saint-Louis Hospital, INSERM U976, Université Paris Diderot-Paris VII, Sorbonne Paris Cité, Paris, France.
7
AP-HP Statistics Department, Saint-Louis Hospital, Université Paris Diderot-Paris VII, Sorbonne Paris Cité, Paris, France.
8
AP-HP Regional Pharmacologilance Center, Fernand Widal Hospital, Université Paris Diderot-Paris VII, Sorbonne Paris Cité, Paris, France.
9
Regional Pharmacovigilance Center of Caen, Caen University Hospital, Caen, France.
10
Department of Clinical Pharmacology, Regional Pharmacovigilance Center of Marseille, Aix-Marseille University, Marseille, France.

Abstract

Anti-PD-1 and anti-CTLA-4 antibodies cause immune-related side effects such as autoimmune type 1 diabetes (T1D). It has also been suggested that by increasing TNF-α, IL-2 and IFN-γ production, anti-PD-1 and/or anti-CTLA-4 treatment could affect pancreatic beta cell function and insulin sensitivity. This study was based on a retrospective observational analysis from 2 July 2014 to 27 June 2016, which evaluated the occurrence of T1D and changes in glycemia and C-reactive protein (CRP) plasma concentrations in patients undergoing anti-PD-1 and/or anti-CTLA-4 treatment for melanoma at the Saint Louis Hospital. All cases of T1D that developed during immunotherapy registered in the French Pharmacovigilance Database (FPVD) were also considered. Among the 132 patients included, 3 cases of T1D occurred. For the remaining subjects, blood glucose was not significantly affected by anti-PD-1 treatment, but CRP levels (mg/l) significantly increased during anti-PD-1 treatment (p = 0.017). However, 1 case of type 2 diabetes (T2D) occurred (associated with a longer therapy duration). Moreover, glycemia of patients pretreated (n = 44) or concomitantly treated (n = 8) with anti-CTLA-4 tended to increase during anti-PD-1 therapy (p = 0.068). From the FPVD, we obtained 14 cases of T1D that occurred during immunotherapy and were primarily characterized by the rapidity and severity of onset. In conclusion, in addition to inducing this rare immune-related diabetes condition, anti-PD-1 treatment appears to increase CRP levels, a potential inflammatory trigger of insulin resistance, but without any short-term impact on blood glucose level.

KEYWORDS:

Adverse events; Anti-PD-1 antibody; Insulin resistance; Melanoma; Type 1 diabetes; Type 2 diabetes

PMID:
29808365
DOI:
10.1007/s00262-018-2178-0
[Indexed for MEDLINE]

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