Persistence of mucosal CAR-T cells and inflammatory remodeling in enterocolitis associated with BCMA CAR-T cell therapy

Multimodal profiling of patients with multiple myeloma who developed enterocolitis after BCMA-directed CAR-T cell therapy showed that the complication is driven by local expansion and persistence of cytotoxic CAR-T cells in the intestinal mucosa, not merely by plasma cell and B cell depletion. The analysis revealed coordinated dysregulation across epithelial, immune and stromal compartments of the gut, pointing to an active inflammatory process rather than a passive immunodeficiency. The inflammatory signatures identified converge on JAK-STAT signalling, providing a mechanistic rationale for JAK inhibitors as a treatment option for this emerging toxicity.