Severe Refractory Immune Effector Cell-Associated Enterocolitis After Ciltacabtagene Autoleucel With Clonal Persistence of CAR-T Construct-Positive T Cells in the Gastrointestinal Tract: A Case Report

Immune effector cell–associated enterocolitis is an emerging delayed toxicity after BCMA-directed CAR-T therapy for multiple myeloma. We report a 69-year-old man with kappa free light chain multiple myeloma and AL amyloidosis who developed severe watery diarrhea, abdominal cramping, anorexia, weight loss, and debility six weeks after ciltacabtagene autoleucel. Initial infectious evaluation was negative. Colonoscopy showed patchy erythema, friability, abnormal vascularity, and ulceration. Biopsies demonstrated epithelial apoptosis, crypt withering and loss, focal active colitis, and no viral inclusions. Subsequent duodenal biopsy showed a prominent CD3-positive mucosal and submucosal T-cell infiltrate with an atypical CD2-positive, CD4-positive, CD5-positive, CD7-loss, CD8-negative immunophenotype. CMV immunohistochemistry was negative. Next-generation sequencing of gastrointestinal tissue detected CAR-T construct fusion transcripts, including TNFRSF9/CD137/4-1BB::CD247 and CD8A::TNFRSF9, with T-cell clonality involving TRBV7-3 and no B-cell clonality. These findings supported clonal persistence or expansion of CAR-T construct–positive T cells in the gastrointestinal tract, although they did not establish overt CAR-T cell lymphoma. His course was complicated by steroid-refractory enterocolitis, pneumatosis intestinalis, pneumoperitoneum, malnutrition, electrolyte derangements, and need for exploratory laparotomy without gross necrosis or frank perforation. He required prolonged bowel rest, total parenteral nutrition, intravenous immunoglobulin, and multimodal immunosuppression including infliximab, vedolizumab, ruxolitinib, tacrolimus, budesonide, systemic corticosteroids, and cyclophosphamide. He gradually improved and was discharged with ongoing parenteral nutrition and immunosuppressive therapy. This case highlights severe refractory immune effector cell–associated enterocolitis after ciltacabtagene autoleucel with biopsy-proven clonal persistence of CAR-T construct–positive T cells in the gut. Tissue-based CAR-T construct testing and T-cell clonality assessment should be considered in severe or refractory post–CAR-T enterocolitis, particularly when biopsies show atypical T-cell infiltrates.