Immune-Related Esophagitis and Duodenitis Secondary to Nivolumab-Ipilimumab Combination Therapy

• Published in: The American journal of gastroenterology Vol. 113; pp. S1031 - S1032
• Main Authors: Wang, Susan, Morales, Shannon, Ren, Bing, Drinane, Mary
• Format: Journal Article
• Language: English
• Published: New York Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins 01.10.2018
• Subjects: Esophagus; Gastroenterology; Histology; Immunotherapy; Kidney cancer; Metastasis; Monoclonal antibodies; Small intestine; Targeted cancer therapy
• ISSN: 0002-9270; 1572-0241

Introduction: Nivolumab and ipilimumab are checkpoint inhibitors that have been increasingly used in advanced malignancies. Both medications commonly cause diarrhea secondary to enterocolitis; however, esophageal involvement has been rarely reported. Here, we report a case of esophagitis and duodenitis in a patient with metastatic renal cell carcinoma treated with nivolumab/ipilimumab combination therapy. Case Description: A 61 year-old man with metastatic renal cell carcinoma on nivolumab/ipilimumab reported nausea and vomiting after every infusion since initiating therapy, but developed diarrhea after his last infusion six weeks into therapy. Laboratory testing revealed a normal CBC and CMP. Infectious evaluation for Clostridium difficile and CMV was negative. CT demonstrated mildly dilated loops small bowel in the left hemi-abdomen without a focal transition point. The patient underwent esophagogastroduodenoscopy and colonoscopy which demonstrated severe esophagitis (Figure 1) and multiple small superficial ulceration in the duodenum to the third portion (Figure 2). The stomach, terminal ileum, and colon were endoscopically normal. Biopsies from the esophagus and duodenum demonstrated active inflammation with diffuse CD3+ T cells composed of both CD4 and CD8+ cells in the mucosa. Villous blunting was also noted on histology. Based on histology, the patient was suspected to have adverse event related to Nivolumab and Ipilimumab combination therapy, and was administered IV methylprednisolone (1.0 mg/kg uptitrated to 2.5mg/kg daily), PPI, and loperamide with improvement in his symptoms. Discussion: Checkpoint inhibitors are novel chemotherapy agents which have demonstrated efficacy against multiple advanced malignancies. However, immune-related adverse events may be over 50%. Ipilimumab has been demonstrated to cause dysregulation of the GI mucosal immunity including duodenum, but has not yet been implicated in a case of esophagitis. There are four case reports of nivolumab induced esophagitis with gastritis. With these agents now approved for combination use, we may start to see new patterns of GI involvement. Our case highlights that the upper GI tract, including the esophagus, can also be involved in immune-mediated adverse events. Upper GI symptoms should be investigated for patients treated with these agents since early recognition may improve response to therapy with steroids.