Immune checkpoint inhibitors (ICIs) have transformed the landscape of oncological therapy, but at the price of immune related adverse events. Among these, checkpoint inhibitor related autoimmune diabetes (CIADM) entails substantial long-term morbidity due to the complex nature of its glycaemic management.
We sought to characterise the disease phenotype of CIADM. Patients who developed CIADM after ICI use were retrospectively identified across Westmead Hospital, Blacktown Hospital, Melanoma Institute Australia and Royal North Shore Hospital. CIADM was defined as new onset hyperglycaemia (random BGL≧11.1mmol/L or HbA1c≧6.5%) and insulin deficiency (C-peptide <0.4nmol/L). Electronic medical records were reviewed.
25 patients with CIADM were identified, making this the second largest series ever reported internationally. Median age was 66 years (IQR 49-83). 68% of patients had melanoma as the primary malignancy. All patients had either anti-PD1 or anti-PDL1 therapy and 44% had this in combination with anti-CTLA4 therapy. 72% of patients had complete or partial oncological response. Median time from ICI commencement to CIADM onset was 19 weeks. 20% had pre-existing type 2 diabetes requiring diet control and/or oral hypoglycaemic agents only. 60% presented with diabetic ketoacidosis at CIADM onset and required ICU admission. 38% of patients were positive for traditional T1D autoantibodies. 10 patients had HLA typing with 3 patients carrying a T1D-risk haplotype and 2 patients with protective haplotypes for T1D. 28% had elevated lipase at presentation. Infliximab was trialled at diagnosis in one patient but was unsuccessful at reversing insulin dependence. All patients remain on insulin, with 3 patients managed with insulin pumps.
CIADM leads to fulminant T1D with a high incidence of diabetic ketoacidosis. In comparison with T1D, there is a lower incidence of T1D autoantibodies and T1D associated haplotypes.