Background

Chimeric antigen receptor T-cell (CAR-T) therapy has significantly improved survival rates for patients with hematologic malignancies, including leukemia, who were previously difficult to treat with conventional drugs. Recently, its application has expanded to autoimmune diseases such as lupus and systemic sclerosis, garnering widespread attention in the medical community. However, due to its mechanism of strongly activating the patient's immune system, unexpected adverse effects can occur. The most common toxic reactions include cytokine release syndrome (CRS), which causes systemic inflammation due to excessive immune response, and immune effector cell-associated neurotoxicity syndrome (ICANS), which causes central nervous system dysfunction. These syndromes are well-known in clinical practice, and their management has become relatively easier due to the establishment of standard response protocols. In contrast, gastrointestinal mucosal inflammation, which has recently been reported, is considered an unknown area due to its unclear pathophysiology. Immune effector cell-mediated enterocolitis (IEC-EC), in which the intestinal mucosa is directly attacked by immune cells, has a low incidence but is a life-threatening toxic reaction that rapidly worsens the patient's prognosis. The medical community is continuously striving to systematically understand the pathophysiology and clinical course of this enterocolitis to ensure patient safety and successfully expand the scope of treatment.

Key Findings

Based on a comprehensive analysis of previously reported patient cases, IEC-EC was found to occur primarily in patients who received B-cell maturation antigen (BCMA)-targeted CAR-T therapy. This enterocolitis is observed in up to 6% of patients treated with BCMA-targeted therapy and is characterized by uncontrolled diarrhea and malabsorption. Examination of the patients' condition through endoscopy and histopathological examination revealed widespread ulcers and severe inflammatory cell infiltration in the intestinal mucosa. Unlike typical infectious enteritis, it shows a tendency to be unresponsive to conventional supportive therapy, such as fluid and nutritional support, making it a highly dangerous condition. Therefore, medical professionals should quickly rule out infectious causes and apply appropriate supportive therapy, including nutritional support, when symptoms occur. For patients whose symptoms persist, a stepwise approach using biological agents or small molecule drugs, which are used in the treatment of inflammatory bowel disease (IBD), is considered an effective solution. Early recognition of adverse effects and the establishment of a collaborative system between hematologists/oncologists and gastroenterologists are critical factors in improving patient prognosis.

Significance and Prospects

This clinical report analysis represents a significant advancement in establishing diagnostic criteria and treatment guidelines for CAR-T adverse effects, which were previously not clearly defined in clinical practice. It demonstrates that even highly effective immunotherapies that lead to patient cure can pose a risk to the gastrointestinal barrier, providing evidence to enhance the safety of the therapy. However, a limitation remains in that there is still no reliable biomarker to predict the risk of IEC-EC. Subsequent genomic analysis studies should be actively conducted to identify which patients are more susceptible to mucosal damage and are likely to experience adverse effects. Furthermore, social discussions should follow to improve treatment guidelines and rationalize reimbursement requirements so that biological agents, which are emerging as an alternative in clinical practice, can be rapidly prescribed for the purpose of alleviating adverse effects. By enhancing collaboration between hematologists/oncologists and gastroenterologists and establishing a monitoring system, it is expected to make a significant contribution to improving patients' long-term survival.