JA Damianos et al. Alimentary Pharmacology & Therapeutics, 2026; 0:1–12. Open Access! 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 revolutionized 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…it has become apparent that rarely, CAR-T can cause gastrointestinal mucosal inflammation, termed immune effector cell-mediated enterocolitis (IEC-EC).”

Other treatments affecting the immune system can result in gastrointestinal inflammation. “Immune checkpoint inhibitors, including cytotoxic T lymphocyte associated anti-gen 4 (CTLA- 4) inhibitors, programmed death-1 (PD1) inhibitors, and PD-ligand 1 (PDL-1) inhibitors have been associated with colitis (with or without enteritis) in up to 54% of patients treated with these agents”

Key points:

• “Occurring in up to approximately 6% of patients typically following B cell maturation antigen-targeted CAR-T therapy, IEC-EC presents with severe diarrhea and malabsorption, responds poorly to treatment, and portends a dire prognosis.”
• “Step-up pharmacotherapy, often featuring biologics and small molecules drawn from the inflammatory bowel disease pharmacologic armamentarium.” Figure 6 presents an algorithm for evaluation and management.
• “Patients typically present 1–3 months after CAR-T infusion with persistent watery, non-bloody diarrhea, often Grade 3 or higher [33]. Diarrhea is often severe and persistent, frequently accompanied by malnutrition and significant weight loss, and may necessitate prolonged parenteral nutritional support [25]. Diagnosis is often delayed due to the rarity and novelty of this condition, and the fact that patients receiving CAR-T have numerous other potential reasons to experience diarrhea.”

My take: There are a growing number of individuals needing CAR-T cell therapy. Recognizing this delayed complication quickly may help improve outcomes.

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