Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy

S. Bowyer, P. Prithviraj, P. Lorigan, J. Larkin, G. McArthur, V. Atkinson, M. Millward, M. Khou, S. Diem, S. Ramanujam, B. Kong, E. Liniker, A. Guminski, P. Parente, M. C. Andrews, S. Parakh, J. Cebon, G. V. Long, M. S. Carlino, O. Klein

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Background:Recent phase III clinical trials have established the superiority of the anti-PD-1 antibodies pembrolizumab and nivolumab over the anti-CTLA-4 antibody ipilimumab in the first-line treatment of patients with advanced melanoma. Ipilimumab will be considered for second-line treatment after the failure of anti-PD-1 therapy.Methods:We retrospectively identified a cohort of 40 patients with metastatic melanoma who received single-agent anti-PD-1 therapy with pembrolizumab or nivolumab and were treated on progression with ipilimumab at a dose of 3 mg kg -1 for a maximum of four doses.Results:Ten percent of patients achieved an objective response to ipilimumab, and an additional 8% experienced prolonged (>6 months) stable disease. Thirty-five percent of patients developed grade 3-5 immune-related toxicity associated with ipilimumab therapy. The most common high-grade immune-related toxicity was diarrhoea. Three patients (7%) developed grade 3-5 pneumonitis leading to death in one patient.Conclusions:Ipilimumab therapy can induce responses in patients who fail the anti-PD-1 therapy with response rates comparable to previous reports. There appears to be an increased frequency of high-grade immune-related adverse events including pneumonitis that warrants close surveillance.

Original languageEnglish
Pages (from-to)1084-1089
Number of pages6
JournalBritish Journal of Cancer
Issue number10
Publication statusPublished - 10 May 2016
Externally publishedYes


  • immune-mediated adverse event
  • ipilimumab
  • metastatic melanoma
  • nivolumab
  • pembrolizumab

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