2734 Immunotherapy-Mediated Hemorrhagic Gastritis After Ipilimumab and Nivolumab Therapy

Abstract

INTRODUCTION: Combined checkpoint inhibitor immunotherapy with ipilimumab (anti-cytotoxic T-lymphocyte antigen 4 antibody) and nivolumab (anti-programmed cell death receptor 1 antibody) has greatly advanced the treatment of multiple malignancies but is associated with increased immune-related toxicities. Gastrointestinal toxicity is one of the most frequent adverse effects, and while lower GI tract toxicity, such as anti-CTLA-4-mediated colitis, is well known, severe toxicity of the upper GI tract is rare and not well described. We report a case of severe hemorrhagic gastritis in a patient after initiation of ipilimumab and nivolumab therapy for metastatic renal cell carcinoma. CASE DESCRIPTION/METHODS: A 70-year-old man with history of metastatic renal cell carcinoma and recent immune-related myocarditis initially presented with myasthenic weakness after receiving single doses of ipilimumab and nivolumab 5 weeks prior. His presentation was most consistent with seronegative, immune-mediated myasthenia gravis-like syndrome. He was treated with intravenous steroids and plasmapheresis. After 9 days of steroid therapy, he developed large volume melena requiring 4 units of blood despite twice-daily proton pump inhibitor therapy. Endoscopic evaluation revealed diffuse, severe inflammation with hemorrhage characterized by adherent blood and erythematous, friable gastric mucosa in the body, antrum, and prepyloric regions. Hemostatic spray was applied as a temporizing measure to control bleeding. Biopsy specimens demonstrated neutrophilic microabscesses with intraglandular apoptotic bodies, increased lymphocytes and scattered neutrophils in lamina propria, and reactive mucosal features. These findings were compatible with checkpoint inhibitor-induced acute gastritis. Immunohistochemical stains for H. pylori and cytomegalovirus were negative. Despite immunosuppressive therapy with high dose steroids, mycophenalate mofetil, and trial of infliximab, he continued to decline with ongoing anemia and progressive weakness. He was transitioned to comfort measures and died soon afterward. DISCUSSION: To our knowledge, this is the first reported case of severe hemorrhagic, non-infectious gastritis as a rare complication of immunotherapy with ipilimumab and nivolumab. Physicians should be aware that checkpoint inhibitor-induced toxicity of the upper GI tract can occur early after initiation of therapy and have a severe, refractory course. Management includes exclusion of infectious process and immunosuppressive therapy.