Review Article: Immune Effector Cell-Mediated Enterocolitis Following CAR-T Cell Therapy-Clinical Features, Pathophysiology and Management.

BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionised the treatment of hematologic malignancies, and its use is expanding rapidly into numerous other disease states including autoimmune diseases. However, CAR-T therapy is associated with a spectrum of immune-related toxicities. In addition to the already well characterized cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, it has become apparent that rarely, CAR-T can cause gastrointestinal mucosal inflammation, termed immune effector cell-mediated enterocolitis (IEC-EC). AIMS: This state-of-the-art review highlights the CAR-T mechanism and details the epidemiology, pathophysiology, clinical manifestations, endoscopic and histopathologic features, and management of IEC-EC. METHODS: This review presents the current state of knowledge through a comperhensive and detailed synthesis of all case series reported in the literature to date. RESULTS: Occurring in up to approximately 6% of patients typically following B cell maturation antigen-targeted CAR-T therapy, IEC-EC presents with severe diarrhoea and malabsorption, responds poorly to treatment, and portends a dire prognosis. Multi-disciplinary management should centre on early diagnosis, supportive cares, assessment and treatment of infections, and step-up pharmacotherapy, often featuring biologics and small molecules drawn from the inflammatory bowel disease pharmacologic armamentarium. CONCLUSIONS: Clinicians should maintain a high degree of vigilance for IEC-EC in patients presenting with gastrointestinal symptoms following CAR-T treatment. Early recognition and multi-disciplinary treatment may improve patient outcomes.