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

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.