P52 Immune-mediated diabetes secondary to the use of immune checkpoint inhibitors

Abstract

Introduction: The use of immune check point inhibitors (ICIs) modified the focus of cancer therapy. ICIs are monoclonal auto-antibodies directed against inhibitory T cell receptors (immune checkpoints), which act as negative co-regulators to limit immune activation. Adverse events related to the endocrine system (irAE) are observed between 4-30%. Immune-mediated diabetes mellitus (DM) is the least frequent complication (less than 1%) but is potentially fatal.

Objectives: To describe the characteristics and frequency of immune-mediated DM in patients with ICIs.

Materials and methods: Retrospective, descriptive, observational study. It included patients of both genders older than 18 years in treatment with ICIs from 2018 to date. Hormone profile and fasting plasma glucose were requested in basal conditions and prior to each infusion. Categorical variables are expressed as a percentage and continuous variables, as median and intercuratil range (IQR).

Results: 72 patients were analyzed, 58% male, median age 66 years (55-74). In our series, immune-mediated DM occurred in 2 patients (2.7%) under combined treatment with ipilimumab + nivolumab. Case 1: 53-year-old female patient. She was diagnosed with diabetic ketoacidosis (DKA) and elevated amylase and lipase x 2, 3 months after starting the ICIs. Lab results were: A1c 6.9%, and a history of altered glucose levels in fasting months before. Case 2: 69-year-old female patient. She was diagnosed with DKA 6 months after starting the ICIs, A1c of 9.3%. History of normal fasting blood glucose levels. Both cases had low C-peptide and negative anti-GAD, anti-insulin, and anti-pancreatic islet antibodies, and neither had pancreatic metastases.

Conclusions: The development of diabetes due to ICIs is rare. The acute evolution of hyperglycemia, in one of our cases coinciding with a fulminant form, associated with DKA and absence of C-peptide, could show the rapid destruction of pancreatic beta cells. The concomitant elevation of pancreatic enzymes could suggest inflammation of the pancreas as a triggering mechanism.It is important to consider this rare but lifethreatening complication of ICIs. In addition, interdisciplinary follow-up, serial blood glucose measurement, and patient education on hyperglycemic guidelines would be good practice for preventing the severity of the condition.