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Cancer Immunology, Immunotherapy

, Volume 66, Issue 11, pp 1399–1410 | Cite as

Autoimmune diabetes induced by PD-1 inhibitor—retrospective analysis and pathogenesis: a case report and literature review

  • Marie-Léa GauciEmail author
  • Pauline Laly
  • Tiphaine Vidal-Trecan
  • Barouyr Baroudjian
  • Jérémy Gottlieb
  • Nika Madjlessi-Ezra
  • Laetitia Da Meda
  • Isabelle Madelaine-Chambrin
  • Martine Bagot
  • Nicole Basset-Seguin
  • Cécile Pages
  • Samia Mourah
  • Philippe Boudou
  • Céleste Lebbé
  • Jean-François Gautier
Original Article

Abstract

Anti-PD-1 antibody treatment is approved in advanced melanoma and provides median overall survival over 24 months. The main treatment-related side effects are immune-related adverse events, which include rash, pruritus, vitiligo, thyroiditis, diarrhoea, hepatitis and pneumonitis. We report a case of autoimmune diabetes related to nivolumab treatment. A 73-year-old man was treated in second line with nivolumab at 3 mg/kg every two weeks for metastatic melanoma. At 6 weeks of treatment, he displayed diabetic ketoacidosis. Nivolumab was withheld 3.5 weeks and insulin therapy was initiated, enabling a normalization of glycaemia and the disappearance of symptoms. Laboratory investigations demonstrated the presence of islet cell autoantibodies, while C-peptide was undetectable. Retrospective explorations on serum banked at week 0 and 3 months before the start of nivolumab, already showed the presence of autoantibodies, but normal insulin, C-peptide secretion and glycaemia. Partial response was obtained at month 3, and nivolumab was then resumed at the same dose. The clinical context and biological investigations before, at and after nivolumab initiation suggest the autoimmune origin of this diabetes, most likely induced by anti-PD-1 antibody in a predisposed patient. The role of PD-1/PD-L1 binding is well known in the pathogenesis of type 1 diabetes. Therefore, this rare side effect can be expected in a context of anti-PD-1 treatment. Glycaemia should be monitored during PD-1/PD-L1 blockade. The presence of autoantibodies before treatment could identify individuals at risk of developing diabetes, but systematic titration may not be relevant considering the rarity of this side effect.

Keywords

Melanoma Anti-PD-1 antibody Autoimmune diabetes Adverse events 

Abbreviations

BMS

Bristol–Myers Squibb

BRAF

Murine sarcoma viral oncogene homolog B1

GADA

Glutamic acid decarboxylase antibody

HbA1c

Glycated haemoglobin Insulinoma antigen-2 antibody

IA2A

Insulinoma antigen-2 antibody

MEK

Mitogen activated protein kinase kinase

NOD

Non-obese diabetic

ZnT8A

Zinc transporter 8 antibody

Notes

Author Contributions

Marie-Léa Gauci, Philippe Boudou, Céleste Lebbé and Jean-François Gautier had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors made substantial contributions to study conception, and subsequent acquisition, analysis and interpretation of data. All authors made substantial scientific and intellectual contributions to the drafting and rewriting of the initial and revised manuscript.

Funding sources

This research did not receive any specific grant from any funding agencies in the public, commercial or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from the participant in the study.

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Marie-Léa Gauci
    • 1
    • 2
    Email author
  • Pauline Laly
    • 1
    • 2
  • Tiphaine Vidal-Trecan
    • 5
    • 6
  • Barouyr Baroudjian
    • 1
    • 2
  • Jérémy Gottlieb
    • 1
    • 2
  • Nika Madjlessi-Ezra
    • 1
    • 2
  • Laetitia Da Meda
    • 1
    • 2
  • Isabelle Madelaine-Chambrin
    • 2
    • 7
  • Martine Bagot
    • 1
    • 2
  • Nicole Basset-Seguin
    • 1
    • 2
  • Cécile Pages
    • 1
    • 2
  • Samia Mourah
    • 2
    • 8
  • Philippe Boudou
    • 3
    • 4
  • Céleste Lebbé
    • 1
    • 2
  • Jean-François Gautier
    • 5
    • 6
  1. 1.AP-HP Dermatology DepartmentSaint-Louis HospitalParis Cedex 10France
  2. 2.INSERM U976, Université Paris Diderot-Paris VIISorbonne Paris CitéParisFrance
  3. 3.AP-HP Hormonology DepartmentSaint-Louis HospitalParisFrance
  4. 4.Université Paris Diderot-Paris VIISorbonne Paris CitéParisFrance
  5. 5.AP-HP Diabetology DepartmentLariboisière HospitalParisFrance
  6. 6.INSERM U1138, Université Paris Diderot-Paris VIISorbonne Paris CitéParisFrance
  7. 7.AP-HP Pharmacology DepartmentSaint-Louis HospitalParisFrance
  8. 8.AP-HP Pharmacogenomic LaboratorySaint-Louis HospitalParisFrance

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