SUN-LB036 Diabetic Ketoacidosis: A Rare Side Effect of Nivolumab Induced Insulin Dependent Diabetes Mellitus

Abstract

Introduction: Nivolumab, is a monoclonal antibody directed against programmed cell death-1 receptor (anti PD-1), and is used in adjuvant treatment of melanoma. With the widespread use of immunotherapies, the incidence of autoimmune diseases referred to as immune related adverse events (irAE) is also increasing. Our case highlights a rare side effect of autoimmune insulin dependent diabetes mellitus (IDDM) related to immunotherapy, in a patient with no detectable diabetes related antibodies. We also review management of this rare side effect. Clinical Case: A 52-year-old woman with a diagnosis of stage IIIC malignant melanoma and no previous history of diabetes mellitus presented with abdominal pain and nausea. She had received 10 doses of Nivolumab as adjuvant therapy for melanoma. She denied any family history of diabetes or autoimmune disorders. Physical exam including vital signs was normal. Lab work up was significant for blood glucose of 280 mg/dl and glycated hemoglobin (HbA1c) was 7.4%, and additional blood work up showed low serum C-peptide 0.5 ng/ml (normal range 1.1-4.4 ng/mL) and negative results were obtained for all islet cell autoantibodies. Arterial blood gas (ABG) revealed high anion gap metabolic acidemia with pH 7.11, pCO2 25 mm Hg, bicarbonate (HCO3) 12 mmol/L, high anion gap 22 and serum lactate 0.8 mmol/L, consistent with diabetic ketoacidosis (DKA). Prior to initiation of Nivolumab, her HbA1c was 5.7%. The patient was diagnosed with DKA due to autoimmune-mediated IDDM secondary to Nivolumab therapy. She was treated with an insulin drip and intravenous fluids after which the anion gap and her symptoms resolved. She was discharged home with a subcutaneous basal bolus insulin regimen. Conclusion: Immunotherapies such as Nivolumab can cause new onset IDDM by inducing autoimmune response. Most likely mechanism of developing IDDM in patients treated with Nivolumab is inappropriate activation of T cells leading to destruction of pancreatic islet cells. Our patient had low serum C-peptide level which correlates with low insulin secretion suggestive of islet cell destruction. Median time of onset of IDDM is 4.4 months after starting Nivolumab. Most common endocrinopathies associated with Nivolumab are hypophysitis, thyroiditis or primary adrenal insufficiency. New onset IDDM is very uncommon irAE, and so far it has been reported in less than 1% of patients. In contrast to other irAE such as colitis there is limited data regarding role of high dose steroids in autoimmune diabetes and it can even exacerbate hyperglycemia and DKA.