Title : A rare case of pembrolizumab-induced severe gastritis
Abstract:
First approved in the United States in 2011, immune checkpoint inhibitors (ICIs) represent a significant advancement in treating various malignancies. The mechanism of action is to prevent inhibition of the host's T cells, thereby allowing them to attack and destroy malignant cells. These therapies have an unprecedented potential benefit of enabling long-term survival in patients with metastatic disease. Notably, ICIs are often associated with potential toxicities that can impact multiple organ systems, which are often autoimmune. Familiarity with these potential immune-related adverse events (irAEs) is crucial for physicians to recognize and intervene early and avoid severe or long-lasting sequelae of such events. For example, we report a rare case of pembrolizumab-induced severe gastritis in a patient with metastatic cervical carcinoma.
The 45-year-old presented to the emergency department in Jan 2017 with dysuria and severe abdominal pain. A CT scan at the time demonstrated a large necrotic right pelvic mass with iliac node involvement. Further biopsy confirmed a well-differentiated, P16-negative squamous cell carcinoma with keratinization and extensive necrosis. She subsequently underwent one course of radiotherapy with concurrent cisplatin therapy and seven cycles of carboplatin/paclitaxel therapy with disease stability until 2018.
Malignancy recurred in 2019, prompting the initiation of pembrolizumab. After completing 19 cycles of pembrolizumab, she developed occasional nausea and vomiting, initially managed effectively with meclizine. However, after initiation of the 40th cycle of pembrolizumab, daily vomiting re-occurred. She was subsequently initiated on omeprazole daily and ondansetron administered before her pembrolizumab infusions. Despite this, her vomiting persisted, with associated dyspepsia and early satiety, which over 12 weeks resulted in a 14-pound unintentional weight loss. She was referred to a gastroenterologist, who initially up-titrated her pre-existing PPI dosage.
However, the patient's symptoms progressed and resulted in her being admitted to the PAH in 2022 for severe vomiting and failure to thrive. Upper endoscopy at the time showed diffuse inflammation, with erythematous, friable, and ulcerated mucosa & overlying white exudate in the gastric body and antrum. Biopsies obtained in the gastric body and the distal gastric antrum and immunohistochemistry confirmed grade lll gastritis.
She was initiated on IV methylprednisolone and IV pantoprazole twice daily with inadequate response to treatment. She was subsequently treated with infliximab 5mg/kg. Given her inability to thrive, she was initiated on total parenteral nutrition. She responded and was discharged home with an oral prednisone taper. Repeat endoscopy demonstrated stable findings, with biopsy results consistent with inflammation due to checkpoint inhibitors. She was diagnosed with severe immune-related gastritis and continued on an oral steroid taper with infliximab therapy.
ICIs have revolutionized the treatment of metastatic malignancies; however, they can trigger various organ - specific irAEs, such as those discussed in this case report. Colitis is ICI therapy's most common gastrointestinal complication; this report represents a rare case of severe gastritis refractory to steroid and biological treatment. A systematic review of all irAEs from 2016 reported 251 irAEs, with 39.7% being gastrointestinal toxicities; however, no GI toxicities were observed in patients taking pembrolizumab. In addition, Hayama et al. report a similar case of pembrolizumab-associated gastritis in a patient who had received 25 cycles of pembrolizumab for a pulmonary adenocarcinoma; in this case, symptoms were relieved by stopping pembrolizumab and initiating oral prednisone.
Audience Take Away:
- Will prompt early investigation of an endoscopic workup for patients on immune-checkpoint inhibitors with atypical symptoms
- Provides multi-disciplinary approach including oncologists, gastroenterologists, and pathologists in involvement of care of patients on immune checkpoint inhibitors
- Provides opportunities for medical and pharmaceutical staff for joined care/collaboration regarding dosing and pharmacokinetics monitoring while on biological agents
- Provides a standardized approach to care with patients on biological agents and checkpoint inhibitors
