Clinical Report: When CAR T Cells Linger in the Gut

Overview

A tissue-based study of enterocolitis after BCMA-directed CAR T-cell therapy for multiple myeloma found inflammatory changes across intestinal T cells, myeloid cells, stromal cells, and epithelium. CAR T cells persisted in intestinal tissue for more than 2 years in one patient, while other cases lacked detectable mucosal CAR T cells, indicating that the observed cases had differing cellular findings. Two patients treated with upadacitinib had improvements in symptoms and selected clinical measures within 4 weeks.

Background

CAR T-associated enterocolitis (CAR-TEC) is a gastrointestinal complication reported after BCMA-directed CAR T-cell therapy. The study examined intestinal samples using single-cell and tissue-based analyses to characterize the local immune and tissue environment in affected patients. Its findings are relevant to understanding why enterocolitis occurs, because some treated patients without enterocolitis had similarly profound B-cell and plasma-cell depletion. The supplied related correspondence discusses whether immune effector cell-associated enterocolitis represents a CAR T-cell lymphoproliferative disorder, while the source article identifies the need for prospective sampling to clarify causality.

Data Highlights

Key Findings

• CAR-TEC samples showed inflammatory changes involving intestinal T cells, myeloid cells, stromal cells, and epithelium.
• Some patients without enterocolitis had similarly profound B-cell and plasma-cell depletion, so depletion alone did not explain the complication in the reported comparison.
• Infiltrating CAR T cells had highly cytotoxic and inflammatory profiles, with activation of interferon and JAK–STAT signaling.
• CAR T cells remained detectable in intestinal tissue for more than 2 years in one patient, although they were no longer detectable in peripheral blood or bone marrow.
• Some patients developed delayed enterocolitis without detectable mucosal CAR T-cell infiltration, consistent with the authors’ consideration of secondary immune dysregulation as another possible mechanism.
• Two patients treated with upadacitinib improved in symptoms, fecal calprotectin, and body weight within 4 weeks; in one patient, intestinal CAR T-cell density decreased from 193 to 39 cells per high-power field.

Clinical Implications

The reported findings describe distinct intestinal inflammatory patterns and do not establish that persistent mucosal CAR T cells cause every case of CAR-TEC. The authors state that prospective sampling before CAR T-cell infusion is needed to better establish causality and assess whether targeting persistent mucosal CAR T cells or downstream inflammatory pathways can improve treatment.

Conclusion

The study maps intestinal immune and tissue changes associated with CAR-TEC and documents prolonged mucosal CAR T-cell persistence in one patient. Its findings also show that detectable mucosal CAR T cells were absent in some cases, and the authors call for prospective studies to clarify mechanisms and treatment approaches.

Related Resources & Content

1. Fortuna et al., PubMed, Year not provided — Persistence of mucosal CAR-T cells and inflammatory remodeling in enterocolitis associated with BCMA CAR-T cell therapy
2. Blood Cancer Journal, 2025 — Is immune effector cell-associated enterocolitis a CAR T-cell lymphoproliferative disorder?
3. Cappell et al., The ASCO Post, 2020 — Long-Term Follow-up of Anti-CD19 CAR T-Cell Therapy in Relapsed B-Cell Malignancies
4. The ASCO Post, 2025 — Patient Immune System Characteristics and Long-Term Remission From CAR T-Cell Therapy in Multiple Myeloma
5. Blood Cancer Journal — Influence of T cell Features on the Efficacy of CAR-T Cell Therapy for Blood Cancers
6. ASTCT Consensus Grading for Toxicities after Immune Effector Cell Therapy
7. Persistence of mucosal CAR-T cells and inflammatory remodeling in enterocolitis associated with BCMA CAR-T cell therapy
8. Cilta-cel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): an updated analysis including overall survival from an open-label, multicentre, randomised, phase 3 trial - PubMed