9185 Pembrolizumab-Induced New-Onset Type 1 Diabetes Mellitus: A Case Report

Abstract Disclosure: D. Teng: None. T.L. Connelly: None. M. Ahmad: None. R. Saeed: None. Introduction: Immune checkpoint inhibitors are becoming essential in the treatment of various cancers. Pembrolizumab is a monoclonal antibody that binds PD-1 receptors, thereby enabling an anti-tumor response by preventing T-cell suppression. Common side effects associated with pembrolizumab include thyroid disorders, hepatitis, pneumonitis, and acute kidney injury, among others. We describe an interesting case of a woman presenting with diabetic ketoacidosis (DKA) in the setting of pembrolizumab-associated new-onset type 1 diabetes mellitus, which was reported at 0.1% during initial clinical trials but is now being increasingly recognized as a complication of immune checkpoint therapy. Case Description: The patient is a 70-year-old female with past medical history notable for stage IIIA vulvar squamous cell carcinoma initially diagnosed and treated in 2017, with recurrence in 2022 and in 2023, at which point pembrolizumab therapy was initiated. Approximately one month after her first dose, the patient presented to the emergency department with palpitations, nausea, non-bloody vomiting, polydipsia, and non-bloody diarrhea. On arrival, the patient’s vital signs were as follows: 97.2 °F, BP 128/74 mmHg, heart rate 80 bpm, respiratory rate 18 per minute, and SpO2 100% on room air. No acute findings were noted on physical exam. Initial blood work was notable for: pH 7.146, lactate 2.4 mmol/L, bicarbonate 8 mmol/L, anion gap 37 mmol/L, creatinine 1.59 mg/dL, glucose 563 mg/dL, C-peptide 0.16 ng/mL, HbA1c 6.9%, and WBC 18.8 B/L with neutrophilic predominance. Urinalysis was notable for 4+ glucose and 4+ ketones. The patient was admitted to the progressive care unit and DKA protocol was initiated including the administration of IV fluids, insulin infusion, and electrolyte replacement. Additional blood work was unrevealing, including insulin autoantibodies <0.4 U/mL, negative islet cell IgG cytoplasmic autoantibodies, and negative anti-GAD65 antibodies. The patient was eventually discharged with outpatient Endocrinology follow-up. Discussion: Immunotherapy is quickly redefining the standard of care in the treatment of several types of malignancies through the leveraging of the body’s immune defense apparatus. Pembrolizumab prevents the deactivation of T-cells via the PD-1/PD-L1 pathway. Unfortunately, this also predisposes non-cancerous cells to autoimmune destruction by these T-cells. It is proposed that such is the mechanism by which pancreatic beta islet cells are destroyed in the setting of pembrolizumab use, thereby resulting in a rapid reduction in insulin production capability. New-onset type 1 diabetes complicated by DKA is potentially life-threatening, and so we believe this case highlights the need for both pre-treatment counseling as well as follow-up screening following initiation of pembrolizumab therapy. Presentation: 6/2/2024