Table 2.

Recommendations for diagnosing and managing IEC-associated enterocolitis.

Diagnosing IEC-associated enterocolitis
Recommendation	Rationale
Consider this entity in patients with unexplained diarrhea following CAR-T, particularly if > 1 month afterward	In our series, the median time to symptom onset (typically Grade 3+ non-bloody diarrhea) was 3 months after CAR-T infusion
(If applicable) Re-refer the patient to the CAR-T treatment center if no longer being followed there actively	Diagnosis of this delayed toxicity requires close consultation between the patient’s primary oncologist and the CAR-T treatment center
Perform endoscopic evaluation with biopsies that are specifically reviewed by a hematopathologist	Infectious causes (e.g., CMV colitis) can occur without viremia, and enteral T-cell malignancies have been reported in this setting [9]
(If applicable) Work with product manufacturers to test for CAR presence on enteral biopsies	If a lymphoproliferative process is suspected, the product manufacturer will be able to assist with CAR staining to evaluate causality

Managing IEC-associated enterocolitis
Recommendation	Rationale
Consult with GI and ID specialists on management and strategies to avoid treatment-related infections	Given the rarity of this toxicity and the immunosuppressive nature of its management, a collaborative approach is imperative
Consider minimizing the use of long-term corticosteroids, particularly if symptoms do not resolve quickly	Long-term corticosteroids can potentially predispose patients to complications such as adrenal insufficiency or bowel perforation
Consider irAE-type management with early infliximab or vedolizumab if symptoms do not resolve quickly	In our series, these biological agents occasionally led to symptom resolution in steroid-refractory cases after 1–3 doses
If symptoms do not resolve with the above steps, revisit the diagnosis of a potential lymphoproliferative process	For patients with lymphoproliferative T-cell processes involving the gut, drugs like cyclosporine may be more effective [12]
For life-threatening cases, consider IEC-HS management strategies including ruxolitinib or chemotherapy	While these agents have not been studied in this setting, they are options in refractory cases of IEC-HS based on expert opinion [4]

All recommendations are based on our experience to date. Further research into diagnostic modalities and therapeutic interventions, ideally studied in a prospective manner, will be important steps to advance our understanding of IEC-associated enterocolitis.

CAR chimeric antigen receptor, CAR-T chimeric antigen receptor T-cell therapy, CMV cytomegalovirus, GI gastroenterology, ID infectious diseases, IEC immune effector cell, irAE immune-related adverse event.