Pathologic changes in ipilimumab-related hepatitis in patients with metastatic melanoma

Dig Dis Sci. 2012 Aug;57(8):2233-40. doi: 10.1007/s10620-012-2140-5. Epub 2012 Mar 21.

Abstract

Ipilimumab is a fully human monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, an immune checkpoint molecule that down-regulates pathways of T-cell activation. Ipilimumab has demonstrated a statistically significant improvement in overall survival in two randomized controlled phase III trials of patients with metastatic melanoma. A main complication of ipilimumab therapy is the development of inflammatory events which can occur in various organs, including the liver (i.e., hepatitis). Hepatic injury is a concern because it can develop with little warning and may potentially be severe. We analyzed liver biopsy findings in 4 cases of ipilimumab treatment-related hepatitis and compared them to a fifth, previously reported case. All 5 patients had a histologic pattern of injury that was similar to what is observed with acute viral and autoimmune hepatitis; however, the findings are not specific and require clinicopathologic correlation. Pathologic evidence of hepatitis resolved in all 5 patients with appropriate immunosuppressive therapy. Although a relatively uncommon adverse event with ipilimumab, patients should be monitored at regular intervals for biochemical/pathological evidence of hepatitis.

Publication types

  • Case Reports
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects*
  • Chemical and Drug Induced Liver Injury / pathology*
  • Fatal Outcome
  • Female
  • Humans
  • Ipilimumab
  • Liver / pathology*
  • Male
  • Melanoma / drug therapy*
  • Middle Aged

Substances

  • Antibodies, Monoclonal
  • Ipilimumab