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This case report details the first instance of colitis induced by valemetostat, an enhancer of zeste homolog 1 and 2 (EZH1/2) inhibitor. Discontinuation of the drug led to symptom resolution, suggesting a link between EZH1/2 inhibition and T cell-mediated colitis.

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EZHdiarrheadrug-induced colitisenhancer of zeste homolog 1 and 2 inhibitorimmune checkpoint inhibitor-induced colitisvalemetostat

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Area of Science:

  • Oncology
  • Gastroenterology
  • Immunology

Background:

  • Valemetostat is an enhancer of zeste homolog 1 and 2 (EZH1/2) inhibitor used in treating relapsed nodal T-follicular helper cell lymphoma.
  • Immune checkpoint inhibitors can induce colitis, characterized by gastrointestinal inflammation.
  • The specific gastrointestinal side effects of EZH1/2 inhibitors are not well-documented.

Purpose of the Study:

  • To report the first case of colitis associated with valemetostat therapy.
  • To investigate the potential mechanism of EZH1/2 inhibitor-induced colitis.
  • To highlight the importance of early diagnosis and management of drug-induced colitis.

Main Methods:

  • A case study of an 80-year-old woman with relapsed T-follicular helper cell lymphoma.
  • Clinical evaluation including colonoscopy and histological biopsy.
  • Immunohistochemical analysis of the colonic biopsy.

Main Results:

  • The patient developed severe watery diarrhea during valemetostat therapy.
  • Colonoscopy revealed diffuse mucosal erythema and edema.
  • Biopsy confirmed lymphoplasmacytic infiltration and crypt abscesses, consistent with colitis. Immunohistochemistry showed CD3-positive T cell predominance with CD8-positive cells.
  • Diarrhea resolved upon discontinuation of valemetostat.

Conclusions:

  • This is the first reported case of enhancer of zeste homolog 1 and 2 (EZH1/2) inhibitor-induced colitis.
  • EZH1/2 inhibition may cause T cell-mediated intestinal injury via epigenetic dysregulation.
  • Patients on EZH1/2 inhibitors experiencing persistent diarrhea require prompt endoscopic and histological evaluation.