Severe CMV Gastritis Associated With Pembrolizumab Therapy

Abstract

Introduction: Immunotherapy with checkpoint protein inhibitors has shown effectiveness in the management of malignancy, including metastatic melanoma. However, use of these medications has been limited by gastrointestinal complications. We report a rare case of severe CMV gastritis associated with pembrolizumab immunotherapy for malignant melanoma. Case: A 72 year old male with stage 4 malignant melanoma, with metastasis to lung and brain, was receiving immunotherapy with the PD-1 inhibitor pembrolizumab. Following 8 cycles of pembrolizumab he was admitted with several weeks of persistent epigastric pain, non-bloody, non-bilious emesis, poor oral intake, and 20 lbs weight loss over one month. A PET-CT scan done prior to admission to assess response of therapy, showed multiple small soft tissue nodules around the lesser curvatures of stomach. An EGD was performed which showed severe desquamative gastritis. The entire stomach appeared edematous, erythematous, friable and erosive, which raised suspicion for immune mediated gastritis. The esophagus and duodenum appeared normal. Pathology revealed severe acute inflammation with almost complete absence of surface mucosa and dense neutrophilic infiltration of the lamina propria and crypts. IHC for CMV was positive. Patient was initially treated with steroids (equivalent to 1 mg / kg prednisone for three weeks with gradual taper), high intensity proton pump inhibitor therapy, as well as valganciclovir for CMV. The patient's symptoms improved and immunotherapy was resumed with pembrolizumab. He had follow up EGDs after 2 months and 1 year with near resolution of gastritis and clearance of CMV gastritis.2667_A Figure 1 No Caption available.2667_B Figure 2 No Caption available.2667_C Figure 3 No Caption available.Discussion: PD-1 inhibitors like nivolumab and pembrolizumab, have been commonly implicated in severe cases of enterocolitis and rarely in esophagitis and gastritis. These adverse effects are immune mediated. Rare cases of CMV activation have also been reported with PD-1 inhibitor therapy. Our case emphasizes that role of viruses like CMV should be suspected in severe cases of gastritis or colitis due to immunotherapy. In our patient immunotherapy was resumed without recurrence of GI symptoms with one year follow-up.