Chimeric antigen receptor (CAR) T-cell therapy-related gastrointestinal toxicity: Histologic features and morphologic mimics

Abstract

Chimeric antigen receptor (CAR) T-cell therapy is a contemporary treatment modality for hematologic malignancies, with potential future applications in solid tumors. While the clinical side effects of CAR T-cell therapy are well-documented, histologic correlations of gastrointestinal (GI) toxicity remain underreported. This study prospectively identified 5 sets of GI biopsies from 3 patients presenting with CAR T-cell therapy-associated GI toxicity. Patients exhibited symptoms such as abdominal pain, hematochezia, non-bloody diarrhea, weight loss, and fever/chills, occurring 1.5–8 months post-therapy. Histologic examination revealed a graft versus host disease (GVHD)-like pattern of injury in colon biopsies, characterized by epithelial apoptosis, crypt dropout, and neuroendocrine cell nests. One duodenal biopsy showed intraepithelial lymphocytosis and villous blunting, mimicking celiac disease. A notable paucity of CD20-positive B-cells and CD38-positive plasma cells was observed in both colonic and small intestinal biopsies. Two patients required biologic agents for treatment, while one patient improved with corticosteroids but succumbed to an upper respiratory infection. The findings underscore the necessity of correlating symptom onset with therapy timing to achieve accurate diagnosis of CAR T-cell therapy-associated GI toxicity.