Comparison of intestinal histopathological changes following teclistamab, BCMA ‐directed CAR T, CD19 ‐directed CAR T and rituximab therapies

Abstract

Aims Immunotherapy‐associated intestinal tract injury is increasingly recognized; however, histological patterns associated with specific agents remain incompletely defined. Data directly comparing CD19‐ and BCMA‐directed CAR T therapies with other B‐cell‐targeted treatments are limited, and histological findings associated with teclistamab in the gastrointestinal tract have not been well described. Methods and results We retrospectively reviewed intestinal biopsies from patients treated with BCMA‐directed CAR T ( n = 23), teclistamab ( n = 8), CD19‐directed CAR T ( n = 31) and rituximab ( n = 11), identifying distinct but overlapping histological patterns. Lamina propria plasma cell depletion was the most prominent finding in BCMA‐targeted therapies (74% BCMA CAR T, 88% teclistamab), occurring at significantly lower rates in CD19 CAR T (32%) and rituximab (27%) cohorts ( P < 0.001). Crypt apoptotic bodies (65% BCMA CAR T, 88% teclistamab, 48% CD19 CAR T, 45% rituximab) and active inflammation (48% BCMA CAR T, 38% teclistamab, 35% CD19 CAR T, 9% rituximab) were also observed. Intraepithelial lymphocytosis, villous blunting, goblet cell depletion and erosion were infrequent. No significant histopathological differences were identified between agents sharing a similar target. Conclusion Intestinal biopsies from patients treated with plasma cell and B‐cell‐targeted immunotherapies showed distinct but overlapping histological patterns. Lamina propria plasma cell depletion was most prominent in BCMA‐directed therapies, while crypt apoptotic bodies and active inflammation were identified across all treatment groups.