The development of immunotherapy has provided patients with metastatic melanoma with improved tumour response and overall survival rates1. However, these medications are associated with unique adverse event profiles, unlike other chemotherapeutic agents.
A 61year male presented in diabetic ketoacidosis (DKA) following sequential therapy with ipilimumab and pembrolizumab for the treatment of metastatic melanoma. He had completed four cycles of ipilimumab and had commenced pembrolizumab following disease progression six weeks prior to his presentation. There was no past history or family history of Type 1 diabetes or other autoimmune conditions.
He was managed according to a standard DKA protocol and subsequently changed to a basal bolus insulin regimen. Antibodies to GAD or IA-2 were negative and C-peptide was 57pmol/L (300-2350pmmol/L). There was biochemical evidence of mild hyperthyroidism (TSH 0.01, T4 26.4) with negative thyroid antibodies. He had normal pituitary function. He was commenced on high doses of glucocorticosteroids (GCS), conventional immunosuppressive therapy for pembrolizumab induced autoimmune adverse effects, in an attempt to salvage beta cell function. His insulin requirements significantly declined with weaning of GCS doses suggesting potential recovery.
Ipilimumab is a monoclonal antibody against CTLA-4 and pembrolizumab, against the Programmed death-1 (PD-1) receptor. They amplify the host cell response against tumoural antigens and have shown superior response rates and overall survival in patients with metastatic melanoma. They are associated with unique immune related adverse effects (IRAE) from non-specific stimulation of the immune system.
The IRAE's are typically managed with high doses of GCS and are mostly reversible. There are only a handful of case reports of pembrolizumab induced T1DM. Beta cell recovery following administration of GCS has not previously been described.
Here we describe a case of DKA in a patient receiving novel immunotherapy for metastatic melanoma . Glucocorticosteroids were used in an attempt to reverse the islet cell IRAE.