CAR T-cell therapy linked to severe inflammatory complications

Researchers are uncovering the biological mechanisms behind severe inflammatory complications associated with CAR T-cell therapy. A study from the Icahn School of Medicine at Mount Sinai, published in Nature Medicine, identified that CAR-T cells can persist in intestinal tissue long after treatment, contributing to enterocolitis in some patients. This condition often manifests as diarrhea, abdominal pain, nausea, and weight loss, particularly in those treated for multiple myeloma.

Separately, clinical data indicates that severe hyperinflammation, specifically immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), remains a fatal complication for some patients. In a study of 301 adults treated with CD19- or BCMA-directed products, IEC-HS occurred in 4.7% of cases. This complication typically emerges around ten days after infusion, often following cytokine release syndrome.

Key predictors for these toxicities include high tumor burden, elevated serum ferritin, and high levels of CAR T-cell expansion. Clinical manifestations often involve hepatic dysfunction, severe cytopenias, and infectious complications such as bacterial bloodstream infections or fungal infections.