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01-08-2018 | Original Article

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

Authors: Marie-Léa Gauci, Philippe Boudou, Barouyr Baroudjian, Tiphaine Vidal-Trecan, Laetitia Da Meda, Isabelle Madelaine-Chambrin, Nicole Basset-Seguin, Martine Bagot, Cécile Pages, Samia Mourah, Matthieu Resche-Rigon, Sylvine Pinel, Marion Sassier, Franck Rouby, Pirayeh Eftekhari, Céleste Lebbé, Jean-François Gautier

Published in: Cancer Immunology, Immunotherapy | Issue 8/2018

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.

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Title: 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
Authors: Marie-Léa Gauci
Philippe Boudou
Barouyr Baroudjian
Tiphaine Vidal-Trecan
Laetitia Da Meda
Isabelle Madelaine-Chambrin
Nicole Basset-Seguin
Martine Bagot
Cécile Pages
Samia Mourah
Matthieu Resche-Rigon
Sylvine Pinel
Marion Sassier
Franck Rouby
Pirayeh Eftekhari
Céleste Lebbé
Jean-François Gautier
Publication date: 01-08-2018
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 8/2018
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-018-2178-0

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