Immune effector cell-associated enterocolitis following chimeric antigen receptor T-cell therapy in multiple myeloma.

Immune effector cell-associated enterocolitis following chimeric antigen receptor T-cell therapy in multiple myeloma. Blood cancer journal Fortuna, G. G., Banerjee, R., Savid-Frontera, C., Song, J., Morán-Segura, C. M., Nguyen, J. V., Lekakis, L., Fernandez-Pol, S., Samraj, A. N., Naresh, K. N., Vazquez-Martinez, M., Baz, R. C., Spiegel, J. Y., Mikkilineni, L., Gubatan, J. M., Sidana, S., de Menezes Silva Corraes, A., Kalariya, N. M., Patel, K. K., Shim, K. G., Fonseca, R., Ferreri, C., Voorhees, P. M., Richard, S., Valdes, C. R., Wolf, J. L., Cowan, A. J., Sborov, D. W., Locke, F. L., Lin, Y., Wang, Y., Hansen, D. K. 2024; 14 (1): 180

Abstract

We report 14 cases of immune effector cell (IEC)-associated enterocolitis following chimeric antigen receptor T-cell (CAR-T) therapy in multiple myeloma, with a 1.2% incidence overall (0.2% for idecabtagene vicleucel and 2.2% for ciltacabtagene autoleucel). Patients developed acute-onset symptoms (typically non-bloody Grade 3+ diarrhea) with negative infectious workup beginning a median of 92.5 days (range: 22-210 days) after CAR-T therapy and a median of 85 days after cytokine release syndrome resolution. Gut biopsies uniformly demonstrated inflammation, including intra-epithelial lymphocytosis and villous blunting. In one case where CAR-specific immunofluorescence stains were available, CAR T-cell presence was confirmed within the lamina propria. Systemic corticosteroids were initiated in 10 patients (71%) a median of 25.5 days following symptom onset, with symptom improvement in 40%. Subsequent infliximab or vedolizumab led to improvement in 50% and 33% of corticosteroid-refractory patients, respectively. Five patients (36%) have died from bowel perforation or treatment-emergent sepsis. In conclusion, IEC-associated enterocolitis is a distinct but rare complication of CAR-T therapy typically beginning 1-3 months after infusion. Thorough diagnostic workup is essential, including evaluation for potential T-cell malignancies. The early use of infliximab or vedolizumab may potentially hasten symptom resolution and lower reliance on high-dose corticosteroids during the post-CAR-T period.

View details for DOI 10.1038/s41408-024-01167-8

View details for PubMedID 39414769

View details for PubMedCentralID 8873238