Pembrolizumab is a monoclonal IgG antibody against Programmed Cell Death (anti-PD 1). It is used in the treatment of metastatic melanoma, metastatic non-small cell lung cancer, Hodgkin lymphoma, and squamous cell carcinoma. It functions by inhibiting apoptosis of lymphocytes and macrophages resulting in a boosted immune response to neoplasmic antigens. Although it is effective against many malignancies, it has been associated with increased risk of developing autoimmune conditions, including thyroid, liver and colon. In this poster, we describe a case of an 84 year old Caucasian woman on Pembrolizumab for metastatic melanoma who developed autoimmune diabetes mellitus. We will briefly review the proposed pathological mechanism of Pembrolizumab induced autoimmunity. We also performed a comprehensive literature search and review of similar case reports.
Our patient presented to the emergency department with polyuria, polydipsia and fatigue after more than 20 cycles of Pembrolizumab. On admission, she had a BSL of 25 mmol/L without ketoacidosis and an HbA1C of 12.3%. Six month prior to presentation she had pre-diabetes with an HbA1c of 6.3%. Her C-peptide was low and she had elevated GAD antibodies. She was commenced on basal bolus insulin, but continued with Pembrolizumab and maintained an ECOG of 1.
To date, there have been only a small number of case reports on Pembrolizumab induced autoimmune diabetes. Our case differs from most of the literature due to the slower onset and progression of diabetes. Other treatment options described in the literature included ceasing Pembrolizumab, which has restored beta cell function in one case. Using corticosteroids to reduced autoimmune destruction of pancreatic beta cells, has been shown to be ineffective.