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

Blood Cancer J. 2024 Oct 16;14(1):180. doi: 10.1038/s41408-024-01167-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Enterocolitis* / etiology
  • Enterocolitis* / immunology
  • Enterocolitis* / therapy
  • Female
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Male
  • Middle Aged
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / immunology
  • Multiple Myeloma* / therapy
  • Receptors, Chimeric Antigen / immunology
  • Receptors, Chimeric Antigen / therapeutic use

Substances

  • Receptors, Chimeric Antigen