Ipilimumab-induced colitis in patients with metastatic melanoma

Melanoma Res. 2015 Aug;25(4):321-7. doi: 10.1097/CMR.0000000000000165.

Abstract

Ipilimumab is used for the treatment of metastatic melanoma and is associated with serious immune-related colitis. We aimed to report the clinical features, treatment, and outcomes of patients with ipilimumab-induced colitis. In this retrospective observational study, we identified patients with unresectable melanoma treated with ipilimumab between March 2011 and September 2013. Diarrhea was assessed using the Common Terminology Criteria for Adverse Events, v3.0. Colitis was defined by diarrhea (grade≥2) requiring steroids with or without endoscopic/histologic/radiologic evidence of colitis. A total of 103 patients with metastatic melanoma treated with ipilimumab were identified. Of these, 30 patients (29%) developed diarrhea (all grades), and 23 patients (22%) developed colitis requiring systemic corticosteroid therapy. The median number of ipilimumab doses before onset of diarrhea was 2 (range, 1-4). Six of 23 patients responded to less than 1 mg/kg daily prednisone alone. Fifteen patients required high-dose oral and/or intravenous prednisone (1-2 mg/kg body weight). Six patients had diarrhea refractory to prednisone; five required rescue therapy with budesonide (9-12 mg daily) and one was treated with infliximab (5 mg/kg, three doses). There was one case of severe diarrhea (grade 3) treated successfully with high-dose budesonide (12 mg) monotherapy. Ipilimumab-induced colitis requires early and aggressive medical therapy. Most patients can be successfully managed with systemic corticosteroids. High-dose budesonide is an attractive steroid-sparing agent, however further studies of its efficacy in this setting are needed. Infliximab should be used in refractory cases to avoid colectomy.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Budesonide / therapeutic use
  • Colitis / chemically induced*
  • Colitis / diagnosis
  • Colitis / drug therapy*
  • Diarrhea / chemically induced
  • Female
  • Humans
  • Infliximab / therapeutic use
  • Ipilimumab
  • Male
  • Melanoma / drug therapy*
  • Middle Aged
  • Prednisone / therapeutic use
  • Retrospective Studies
  • Skin Neoplasms / drug therapy*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Ipilimumab
  • Budesonide
  • Infliximab
  • Prednisone