Review Article: Immune Effector Cell‐Mediated Enterocolitis Following
CAR
‐T Cell Therapy—Clinical Features, Pathophysiology and Management
John A. Damianos, Yi Lin, Zongming Eric Chen, Kenneth J. C. Lim, Navreet M. Chowla ABSTRACT
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.