S4250 Development of Immune Checkpoint Inhibitor-Induced Eosinophilic Esophagitis in a Patient on Non-Eosinophilic Esophagitis Dupilumab Dosing

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but are associated with immune-related adverse events (irAEs). ICI-induced eosinophilic esophagitis (EoE) is a rare irAE. Data on managing ICI-induced EoE, particularly with dupilumab, are lacking. We present a case of ICI-induced EoE in a patient on non-EoE dosing of dupilumab, an IL-4Rα antagonist, who achieved clinical, endoscopic, and histologic remission following sustained ICI discontinuation. Case Description/Methods: A 66-year-old woman with a history of metastatic melanoma, status post nivolumab/ipilimumab initiation followed by maintenance nivolumab, and gastroesophageal reflux disease (GERD) on famotidine, presented with abnormal esophageal activity on positron emission tomography (PET)/computed tomography (CT). She had recently completed 26 ICI cycles 3 months prior. PET/CT showed moderately increased metabolic activity in the distal esophagus. Notably, ICI course was complicated by dermatitis and pruritis, managed with dupilumab 300 mg once every 2 weeks (q2w). Dupilumab was initiated for skin irAE, starting 1 year before ICI completion and continuing until 10 months post-ICI completion. In retrospect, 3 months after being on q2w dupilumab for skin irAE, she developed mild dysphagia to solids, despite GERD being controlled with famotidine. Esophagogastroduodenoscopy (EGD) performed for nausea and vomiting at 10 months on q2w dupilumab showed a normal esophagus; no esophageal biopsies were taken at that time. Five months later, for the abnormal esophageal PET/CT activity at 3 months post-ICI completion and a 1-year history of dysphagia, EGD revealed esophageal edema, furrows, and exudates; biopsies showed 40 eosinophils per high-power field (eos/hpf), consistent with EoE. Off ICI, she continued non-EoE q2w dupilumab for both skin irAE and EoE, along with famotidine for GERD. A 6-month repeat EGD at 10 months post-ICI completion showed a normal esophagus with a resolution of EoE features and histologic remission at 0-1 eos/hpf. She discontinued dupilumab subsequently but remained in clinical remission; a surveillance EGD is pending. Discussion: While studies have shown that dupilumab improves EoE histologically, even at non-EoE dosing, concurrent use of q2w dupilumab did not prevent ICI-induced EoE pathology in this case. This patient achieved clinical, endoscopic, and histologic remission only after increased time away from ICI discontinuation, suggesting that non-EoE dupilumab dosing alone may be insufficient for preventing ICI-induced EoE. Further research is needed to guide the prevention and management of ICI-induced EoE.