SAT-661 The Lesser Evil: Pembrolizumab Induced Remission of Metastatic Melanoma with Autoimmune Diabetes, Hypothyroidism, and Colitis

Abstract

Background: Immune checkpoint inhibitors (ICI) are a new class of immunotherapy agents that empower the innate immune system to destroy cancer cells by overcoming checkpoints against autoimmunity and self-tolerance. ICI use against certain cancers has yielded impressive results. Pembrolizumab, an ICI approved by the FDA in 2014 for treatment of metastatic melanoma, is a monoclonal antibody which binds the programmed cell death protein 1 (PD1) receptor, blocking it’s activation. Recent case reports have demonstrated a link between pembrolizumab and severe immunotherapy related adverse events including the incidence of autoimmune disorders. Clinical Case: A 68-year-old male with hypertension and a past medical history of cutaneous melanoma treated fifteen years earlier with tumor resection was started on pembrolizumab after identification of new metastases to the lung and bones. After 3 cycles of therapy he began to experience dizziness, lightheadedness, and vision changes with diarrhea. Outpatient labs demonstrated hyperkalemia with hyponatremia. He was directed to the emergency department by his oncologist for presumed adrenal insufficiency, where he received one dose of IV dexamethasone (4 mg). Repeat labs demonstrated severe diabetic ketoacidosis with elevated blood glucose 981 (70-99 mg/dL), pH 7.19 (7.32-7.42), anion gap of 37 (4-15 mmol/L), and betahydroxybutyrate > 9.00 (0.00-0.40 mmol/L). Following endocrinology consultation steroids were discontinued in favor of iv insulin and fluid resuscitation, with admission to the medical intensive care unit. Further lab testing demonstrated low C-peptide levels and positive IA-2 and GAD-65 antibodies, confirming autoimmune diabetes. Endoscopic biopsy was also consistent with autoimmune colitis, and TSH one month after discharge was 123.70 (0.30-5.00 mcIU/mL) with free T4 < 0.1 (0.6-1.6 ng/dL). Despite early discontinuation of anti-PD1 therapy the melanoma has remained in remission for three years, suggesting a sustained immune response. He continues to require insulin and thyroid hormone replacement, though the autoimmune colitis has resolved. Conclusion: This case demonstrates the overall benefit of immune checkpoint inhibitor therapy in the treatment of metastatic melanoma, while highlighting a potentially lethal therapy complication with the concurrent onset of multiple autoimmune processes affecting separate organ systems. Increased awareness of the potential for DKA in patients not previously diagnosed with diabetes is needed to avoid delays in care and improve outcomes. This case also suggests a potential benefit to integrating routine blood glucose monitoring in immune checkpoint inhibitor treatment protocols, the utility of which should be further investigated.