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.