1806 When the Cure Is the Cause: Checkpoint Inhibitor-Induced Lymphocytic Esophagitis

Abstract

INTRODUCTION: Immune checkpoint inhibitors are a group of novel treatment agents that are used for the treatment of multiple metastatic malignancies. Among these are programmed cell death 1 receptor (PD-1) antibodies that promote T cell proliferation, activating the immune response to tumor cells as well as non-tumor cells causing immune-related adverse events (irAEs). Diarrhea and colitis are common irAEs. Upper gastrointestinal involvement is rare with esophagitis limited to only case reports. CASE DESCRIPTION/METHODS: A 74-year-old female with metastatic renal cell carcinoma developed throat pain and dysphagia after 10 doses of Nivolumab. Proton pump inhibitor (PPI) and viscous lidocaine improved her symptoms. After 20 doses of therapy she developed odynophagia and dysphagia to both liquids and solids. She underwent an esophagogastroduodenoscopy which revealed esophagitis of 13 cm in length, manifest as circumferential erythema and exudate. Biopsy confirmed active esophagitis with dyskeratotic keratinocytes and lymphoplasmacytic infiltrate. Immunohistochemistry demonstrated markedly increased polyclonal plasma cells. This was consistent with nivolumab-induced esophagitis. Nivolumab was discontinued and she was started on methylprednisolone, with rapid improvement in symptoms and subsequent transition to prednisone. She was treated with a prolonged 3-month taper, but her dysphagia to solids recurred 2 months after completing the steroids. Repeat endoscopic biopsies were consistent with reflux esophagitis. She was treated with topical steroids for suspected residual Nivolumab-induced esophagitis as well as PPI with improvement in symptoms. Ten months later, the patient developed dyspepsia and early satiety. Repeat endoscopy showed discolored, linearly eroded, friable, sloughing mucosa. Biopsies taken revealed active and chronic esophagitis with lymphocytic infiltrate again consistent with Nivolumab-induced esophagitis. The patient symptomatically improved with sucralfate and PPI, and treatment was not further escalated. DISCUSSION: This is a rare case of Nivolumab-induced esophagitis demonstrating initial improvement with prolonged steroid taper followed by recurrent symptoms and persistent endoscopic disease treated with acid suppression, sucralfate and topical steroids. For refractory symptoms of esophagitis, immunosuppressants such as Infliximab could be considered. It is important to recognize the diversity and severity of immune-related adverse events to avoid incomplete treatment or a delay in therapy.