SAT-565 - A Checkpoint Gone Awry: Autoimmune Diabetes Following Cemiplimab Therapy

Introduction:
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that enhance antitumor immunity by blocking inhibitory immune pathways. Cemiplimab is a programmed cell death protein-1 (PD-1) inhibitor that augments T-cell–mediated immune responses by preventing T-cell inactivation. While ICIs provide substantial oncologic benefit, they are associated with immune-related adverse events (IrAEs), including endocrinopathies affecting the pituitary, thyroid, adrenal glands, and pancreas. Autoimmune diabetes mellitus is a rare endocrine IrAE. We present a case of autoimmune diabetes presenting as diabetic ketoacidosis (DKA) shortly after initiation of cemiplimab therapy.

Case Presentation:
A 75-year-old woman with cutaneous squamous cell carcinoma of the bilateral lower extremities presented with a one day history of altered mental status and slurred speech. Family reported she was at baseline the prior evening but awoke confused with hallucinations and dysarthria. Examination revealed lethargy, orientation to self and time but not place, dry mouth, and polyuria. She denied prior history of diabetes. One month earlier, cemiplimab therapy was initiated for cutaneous squamous cell carcinoma.
Vital signs demonstrated tachycardia. Laboratory evaluation showed glucose 623 mg/dL, bicarbonate 5.1 mmol/L, anion gap 28, beta-hydroxybutyrate >8.0 mmol/L, and hemoglobin A1c 8.4%, consistent with DKA. Autoimmune testing revealed elevated glutamic acid decarboxylase-65 antibodies and low C-peptide, with negative IA-2 and insulin antibodies. Stroke evaluation was negative.
Clinical Course:
The patient was treated with standard DKA protocol with resolution of metabolic abnormalities and improvement in mental status. Cemiplimab was discontinued with plans for alternative chemotherapy. She was discharged on basal-bolus insulin therapy and remains insulin dependent.

Discussion:
Endocrine IrAEs from ICIs are thought to result from immune-mediated endocrine destruction due to loss of immune tolerance driven by enhanced T-cell activation and impaired regulatory T-cell function. PD-1 inhibition may precipitate cytotoxic T-cell–mediated pancreatic beta-cell apoptosis, resulting in abrupt insulin deficiency. Thyroid dysfunction is the most common cemiplimab related endocrinopathy at ~11%, while ICI associated diabetes remains rare at < 1%. When present, diabetes typically has an acute onset with DKA, low or absent C-peptide, and pancreatic autoantibodies in a subset of cases.
Teaching Point:
ICI–associated diabetes may present abruptly without prior dysglycemia and rapidly progress to diabetic ketoacidosis; early recognition, routine glucose monitoring after ICI initiation, and timely management are essential to reduce morbidity and prevent life-threatening complications.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*