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

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.

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Publication Details

Journal
Blood Cancer Journal
Published
2024-10-16
DOI
https://doi.org/10.1038/s41408-024-01167-8
Citations
40
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
11.30

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article

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

Rafaël Fonseca, Jeffrey L. Wolf, Carlos Moran Segura, Jinming Song et al.
40 citations
Blood Cancer Journal
CAR-T cell therapy research
11.30
article

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

Rafaël Fonseca, Jeffrey L. Wolf, Carlos Moran Segura, Jinming Song, Surbhi Sidana, Frederick Lundry Locke, Rahul Kumar Banerjee, Cesar Rodriguez Valdes, Annie N. Samraj, Gliceida Galarza Fortuna, Kikkeri N. Naresh, Lekha Mikkilineni, Jay Y. Spiegel, Shambavi Richard, Doris K. Hansen, Douglas W. Sborov, Sebastian Fernandez‐Pol, Sireesha Asoori, Krina K. Patel, John Gubatan, Kevin G. Shim, Peter Michael Voorhees, Nilesh Kalariya, Rachid Baz, Lazaros J. Lekakis, Christopher J. Ferreri, Constanza Savid-Frontera, Jonathan V. Nguyen, Mariola Vazquez‐Martinez, Yi Lin, Andre De Menezes Silva Corraes, Yinghong Wang, Andrew J. Cowan
article en
40 citations

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.

Blood Cancer JournalVol. 14(1)
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), The University of Texas MD Anderson Cancer Center (US), University of Miami (US), Palo Alto University (US), University of California, San Francisco (US), University of Washington (US), University of Utah (US), Huntsman Cancer Institute (US), Moffitt Cancer Center (US), Fred Hutch Cancer Center (US), Levine Cancer Institute (US), Mayo Clinic in Arizona (US), Tisch Hospital (US), Sylvester Comprehensive Cancer Center (US), Tisch Cancer Institute, Stanford University (US)
Moffitt Cancer Center, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 1%
CAR-T cell therapy research
11.30
DOIOpen Access PDFOpenAlex
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