Abstract #1401677: Pembrolizumab Induced Autoimmune Diabetes Mellitus

Abstract

Immune checkpoint inhibitors (ICIs) are integral in the treatment of a myriad of malignancies. While ICIs have significantly improved outcomes and cancer survivorship, they have also been implicated in immune related adverse events (irAEs), particularly autoimmune endocrinopathies. Common ICI associated endocrine disorders include hypothyroidism, hyperthyroidism, and primary adrenal insufficiency but rarely diabetes mellitus (DM). ICI induced DM is defined as severe and persistent insulin deficiency after treatment with an ICI. Here, we present a rare case of pembrolizumab induced DM presenting with hyperglycemic hyperosmolar state (HHS). A 77-year-old male with a past medical history of prediabetes on no medical therapy and melanoma of the right upper extremity was admitted with progressive polydipsia, polyuria and acute encephalopathy. Notably, the patient completed two cycles of pembrolizumab two weeks prior to admission. Initial workup demonstrated a glucose of 837 mg/dL (65-99), anion gap of 10 (3-11), small amounts of serum acetone and beta hydroxybutyrate, and a serum osmolality of 369 mOsm/kg (279-295). Venous blood gas revealed a pH of 7.33 (7.31-7.41), pCO2 45 mmHg (41-51), HCO3 24 mEq/L (23-29). Objective data supported the diagnosis of HHS. Hemoglobin A1c prior to initiation of pembrolizumab was 6.1% (< 5.7%) and on admission was 9.1%. He improved with intravenous insulin and fluids. After transition to basal/bolus insulin the patient’s fasting glucose was 126 mg/dL (65-99) with a c-peptide level of 0.41 ng/mL (0.80-3.85), consistent with insulin insufficiency. Glutamic acid decarboxylase 65 autoantibodies were positive, while islet cell and IA-2 autoantibodies were negative. Pembrolizumab was discontinued after the diagnosis of ICI induced DM was established. Our case highlights the unique course of a patient with prediabetes on pembrolizumab who developed ICI induced DM. Pembrolizumab (anti PD-1 monoclonal antibody) can cause an abnormal cytotoxic T cell (CD8+ T cell) mediated beta cell destruction and development of ICI induced DM. ICI induced DM shares characteristics of Type 1 DM with positive autoantibodies and insulin insufficiency. Insulin deficiency often precipitates diabetic ketoacidosis which was not seen in our patient. Given low but detectable c-peptide levels, our patient was likely insulin insufficient and not yet insulin deficient. This case highlights the importance of closely monitoring patients on ICIs, especially those with a predisposition to DM. In patients receiving immunotherapy, early identification of adverse events and risk stratification is essential in reducing morbidity and providing comprehensive care.