Diabetes mellitus induced by PD-1 and PD-L1 inhibitors: description of pancreatic endocrine and exocrine phenotype
Résumé
AIMS: Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors restore antitumor immunity, but many autoimmune side-effects have been described. Diabetes mellitus is a rare complication, and little data concerning its pathophysiology and phenotype have been published. This study aimed to describe both pancreatic endocrine and exocrine functions, immunological features and change in pancreas volume in subjects with diabetes mellitus induced by PD-1 and PD-L1 inhibitors. METHODS: We analyzed the data of six subjects treated with immunotherapy who presented acute diabetes. RESULTS: There were five men and one woman. Median age was 67 years (range 55-83). Three subjects were treated with nivolumab, two with pembrolizumab and one with durvalumab. Median time to diabetes onset after immunotherapy initiation was 4 months (range 2-13). Four patients presented fulminant diabetes (FD); none of these had type 1 diabetes (T1D)-related autoantibodies, none of them had T1D or FD-very high-risk HLA class II profiles. The bi-hormonal endocrine and exocrine pancreatic failure previously reported for one FD patient was not found in other FD subjects, but glucagon response was blunted in another FD patient. Pancreas volume was decreased at diabetes onset in 2 FD patients, and all patients presented a subsequent decrease of pancreas volume during follow-up. CONCLUSIONS: In the patients presented herein, immunotherapy-induced diabetes was not associated with T1D-related autoantibodies. The hormonal and morphological analysis of the pancreatic glands of these six cases contributes to the understanding of the underlying and probably heterogeneous mechanisms. There is a need to find biomarkers to identify patients at risk to develop these new forms of diabetes at early stages of the process to prevent ketoacidosis and to evaluate preventive strategies.
Mots clés
Aged
80 and over
Alpha-cell pancreatic function
Anti-PD-1
Anti-PD-L1
Antibodies
Monoclonal
Humanized/adverse effects
Monoclonal/adverse effects
Autoantibodies/blood
Autoimmune diabetes
B7-H1 Antigen/antagonists & inhibitors/*immunology
Beta-cell pancreatic function
Diabetes mellitus
Diabetes Mellitus/*chemically induced/pathology
Exocrine pancreatic function
Female
Fulminant diabetes
Humans
Immune checkpoint inhibitors side-effects
Immunotherapy
Immunotherapy/*adverse effects
Islets of Langerhans/*drug effects/metabolism/pathology
Male
Middle Aged
Mixed meal test
Nivolumab/adverse effects
Pancreas volume
Pancreas
Exocrine/*drug effects/metabolism/pathology
Phenotype
Programmed Cell Death 1 Receptor/antagonists & inhibitors/*immunology
Programmed cell death-1
Programmed death ligand 1