Complications Of Checkpoint Inhibitors Research Articles

Immune-Related Neuromuscular Complications of Checkpoint Inhibitors

Immune checkpoint inhibition for treatment of metastatic cancers is recognized to cause diverse immune-mediated neurological syndromes. This review will discuss current knowledge about the frequency and varied presentation of these syndromes affecting the peripheral nervous system as well as detail important diagnostic and management considerations. Immune-related adverse events affect the peripheral nervous system more often than the central nervous system, and rates are likely underestimated. Most data regarding neurological immune–related adverse events are retrospective, and prospective studies are needed. These immune-mediated peripheral nervous system syndromes can be severe and contribute to mortality. Discontinuation of ICI therapy combined with aggressive medical management can improve outcomes. Data to inform evidence-based treatment approaches, particularly in moderate to severe events, are needed. It is important to recognize the association between immune-mediated peripheral nervous system syndromes and immune checkpoint therapy. These syndromes can be phenotypically diverse, but conditions such as acquired demyelinating neuropathy, myositis, and myasthenia gravis predominate. It is important for neurologists to recognize and promptly diagnose these conditions and manage these patients in a multidisciplinary setting to improve outcomes.

2752 Nivolumab-Induced Hemorrhagic Gastroduodenitis

INTRODUCTION: Immune Checkpoint Inhibitors are a growing class of cancer immunotherapy agents used to treat a range of malignancies including melanoma, lung cancer, & Hodgkin’s lymphoma. With their increased use, a number of gastrointestinal side effects have been recognized with the most common being colitis and pancreatitis. Few previous case reports have characterized gastroduodenitis as a complication of checkpoint inhibitors. We describe a case of severe hemorrhagic gastroduodenitis secondary to nivolumab, a PD-1 checkpoint inhibitor. CASE DESCRIPTION/METHODS: A 66-year-old female with history of Stage IV non-small cell lung cancer having recently received her fourth dose of nivolumab presented with one week of nausea, vomiting, and abdominal pain. The pain was sharp, 8 out of 10 in intensity, epigastric, non-radiating, and episodic. It was associated with nausea and non-bloody, non-bilious vomiting. There was no history of NSAID or alcohol use. Upon arrival to emergency department her blood pressure was 104/62 mmHg, heart rate 88 bpm, and temperature 36.7 degrees Celsius. She had epigastric tenderness without rebound or guarding. Laboratory workup revealed a normal complete metabolic profile and complete blood count. Her lipase was elevated at 394 IU/L (78 IU/L upper limit of normal.) A CT abdomen/pelvis demonstrated moderate diffuse gastric wall thickening with mucosal hyperenhancement, and mild peripancreatic edema. Patient was initially treated for pancreatitis with intravenous fluids and pain control. She continued to have severe epigastric pain on Day 4 of admission, thus upper endoscopy was pursued. Upper endoscopy showed diffuse severe inflammation with hemorrhage characterized by congestion, erythema, and friability in the entire examined stomach, and moderately diffuse erythema without hemorrhage in the duodenal bulb. Biopsies showed severe chronic active gastritis and were negative for H. pylori. She was started on prednisone 1 mg/kg daily, and symptoms improved. She was discharged to home with close oncology follow up. DISCUSSION: The increasing use of immune checkpoint inhibitors has led to a rising rate of immune-related adverse events affecting the gut. While gastroduodenitis is an uncommon side effect in comparison to colitis or pancreatitis, more cases are being reported in the literature. Early recognition of symptoms in relation to immunotherapy is important in providing timely removal of offending agent and treating appropriately.