To characterize intestinal changes associated with CAR T-associated enterocolitis (CAR-TEC) after BCMA-directed CAR T-cell therapy.
Approach:
Methods: Researchers used single-cell and tissue-based analyses of intestinal samples from patients who developed CAR-TEC after CAR T-cell therapy for multiple myeloma.
Comparison: Findings were considered alongside CAR T-treated patients without enterocolitis, including patients with substantial B-cell and plasma-cell depletion.
Key Findings:
CAR-TEC involved inflammatory changes across T cells, myeloid cells, stromal cells, and intestinal epithelium; B-cell and plasma-cell depletion alone did not explain the complication.
Intestinal samples contained infiltrating CAR T cells with cytotoxic and inflammatory profiles, alongside activation of interferon and JAK–STAT signaling.
In one patient, CAR T cells remained detectable in intestinal tissue more than 2 years after infusion despite being undetectable in blood and bone marrow.
Some patients had delayed enterocolitis without detectable mucosal CAR T-cell infiltration, suggesting that not all cases were directly driven by persistent CAR T cells.
Two patients treated with upadacitinib showed improvements in symptoms, fecal calprotectin, and body weight within 4 weeks. In one, intestinal CAR T-cell density decreased from 193 to 39 cells per high-power field.
Interpretation:
The study authors described a detailed map of intestinal changes in CAR-TEC and identified biological pathways that may be therapeutically targetable. They noted that prospective sampling is needed to establish causality and assess approaches targeting persistent mucosal CAR T cells or downstream inflammation.
Limitations:
The findings came from intestinal samples of patients who developed CAR-TEC; the context does not provide the sample size.
Upadacitinib outcomes were reported for two patients, and the context does not establish treatment efficacy.
Prospective sampling before CAR T-cell infusion is needed to better establish causality.
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