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Review Article: Immune Effector Cell-Mediated Enterocolitis Following CAR-T Cell Therapy-Clinical Features,
John A Damianos1,2, Yi Lin3, Zongming Eric Chen4
1Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
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.
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