Researchers at the Icahn School of Medicine at Mount Sinai have identified biological mechanisms that may contribute to CAR-T cell-associated enterocolitis, a rare but serious intestinal complication following CAR-T therapy for multiple myeloma.
Published in Nature Medicine, the study found that CAR-T cells can persist in intestinal tissue after treatment. Patients who developed enterocolitis also showed widespread changes in the intestinal immune environment, affecting immune cells, intestinal tissue and blood vessels.
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Researchers identified increased JAK-related inflammatory signaling as a potential therapeutic target. In two patients, treatment with the JAK1 inhibitor upadacitinib was associated with improvements in symptoms and intestinal inflammation.
“CAR-T therapy has transformed outcomes for many patients with blood cancers, but as these treatments become more widely used, we are also learning more about their long-term effects on the immune system,” said Saurabh Mehandru, MD, Professor of Medicine (Gastroenterology) at the Icahn School of Medicine at Mount Sinai and corresponding author of the study. “Our research provides the first detailed map of what happens in the intestine in patients who develop CAR-T-associated enterocolitis and identifies biological pathways that may be targeted therapeutically.”
The findings could help researchers better understand, treat and potentially prevent this complication of CAR-T therapy.
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“As we use these therapies in more patients and earlier in the course of disease, it is increasingly important to understand and manage the complications that can occur,” said Samir Parekh, MD, Professor of Medicine and Director of the Center of Excellence for Multiple Myeloma at the Icahn School of Medicine at Mount Sinai, and co-supervisor of the study. “These findings provide important insight into why rare patients develop severe intestinal inflammation and point to potential strategies for treating or preventing this complication.”
