8099 Pembrolizumab Induced Autoimmune Diabetes: An Abrupt Virulent Onset

Abstract Disclosure: H.F. Belal: None. N. Shaykh: None. A. Rajesh: None. J.M. Chehade: None. Background: Pembrolizumab is a programmed cell death protein 1 inhibitors (PD-1i) approved for the treatment of many solid cancers. Although thyroid abnormalities are among the most common endocrine adverse effects associated with PD-1i, insulin-dependent diabetes mellitus can also occur in up to 1% of patients treated with PD1-i.[1] Clinical Case: A 70-year-old female with past medical history of non-toxic multi-nodular goiter and surgical hypothyroidism was diagnosed with gastric cancer. She had no pancreatic abnormality on PET scan. Her management included four cycles of neo-adjuvant chemotherapy: fluorouracil, cisplatin, trastuzumab and pembrolizumab. She had no personal history of gestational diabetes. Prior to initiating neo-adjuvant chemotherapy her A1c was 5.9%. She was not prescribed any anti-diabetic medications. Her grandmother had type 2 diabetes mellitus. On exam her BMI was 23.73 kg/m². She had no acanthosis nigrans, skin tags or abdominal striae. Eighteen days after completing her second cycle of neo-adjuvant chemotherapy, she presented to the emergency department with nausea, vomiting, polyuria and confusion and was found to be in DKA. Her A1c during admission was 7.1%. Imaging revealed no pancreatitis. Labs showed suppressed C-peptide <0.1 ng/mL (1.1-4.4) in the setting of blood glucose 283 mg/dL (71-99). Her GAD-65 antibody was elevated at 902 U/mL (0.0-5.0). She was diagnosed with PD-1i induced autoimmune diabetes mellitus (PD-1i DM) and subsequently treated with basal and prandial insulin. Conclusion: The mechanism of PD-1i DM is unclear. A proposed mechanism is aberrant T cell activation towards pancreatic islet cells. One study found that 59% of patients with PD-1i DM presented with DKA.[1] In this study, the median time of PD-1i DM onset was 20 weeks after the first treatment cycle. Additionally, 40% of these patient had at least one positive pancreatic autoantibody. A recent meta-analysis found the relative risk of PD-1i DM to be 1.56 (95% CI = 0.95-2.57, P = 0.08).2 This relative risk increased to 2.06 (95% CI = 0.48-8.86, P = 0.33) when PD-1i were combined with cytotoxic T lymphocyte antigen-4 inhibitors. References: 1. Stamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H, Weiss SA, Gettinger S, Sznol M, Young A, Rushakoff R, Lee J, Bluestone JA, Anderson M, Herold KC. Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors. Diabetes. 2018 Aug;67(8):1471-1480. doi: 10.2337/dbi18-0002. Epub 2018 Jun 24. PMID: 29937434; PMCID: PMC6054443. 2. Vardarli I, Tan S, Brandenburg T, Weidemann F, Görges R, Herrmann K, Führer D. Risk and incidence of endocrine immune related adverse effects under checkpoint inhibitor mono or combination therapy in solid tumors: a meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2023 Nov 15:dgad670. doi: 10.1210/clinem/dgad670. Epub ahead of print. PMID: 37967245. Presentation: 6/2/2024