Long-term survival and immunological parameters in metastatic melanoma patients who responded to ipilimumab 10 mg/kg within an expanded access programme

Cancer Immunol Immunother. 2013 Jun;62(6):1021-8. doi: 10.1007/s00262-013-1418-6. Epub 2013 Apr 17.


Background: Ipilimumab can result in durable clinical responses among patients with advanced melanoma. However, no predictive marker of clinical activity has yet been identified. We provide preliminary data describing the correlation between immunological parameters and response/survival among patients with advanced melanoma who received ipilimumab 10 mg/kg in an expanded access programme.

Methods: Patients received ipilimumab 10 mg/kg every 3 weeks (Q3W) for four doses (induction) and Q12W from week 24 (W24) as maintenance therapy. Tumor assessments were conducted Q12W. Expression of inducible T cell costimulator (ICOS) on CD4(+) and CD8(+) T cells was assessed at baseline, W7, W12 and W24, and the ratio between absolute neutrophils (N) and lymphocytes (L) determined at baseline, W4, W7 and W10.

Results: Median overall survival among 27 patients was 9.6 months (95 % CI 3.2-16.1), with 3- and 4-year survival rates of 20.4 %. Five patients survived >4 years. Patients with an increase in the number of circulating ICOS(+) T cells at W7 were more likely to experience disease control and have improved survival. An N/L ratio below the median at W7 and W10 was also associated with better survival compared with an N/L ratio above the median.

Conclusions: Ipilimumab can induce long-term survival benefits in heavily pretreated patients with metastatic melanoma. Changes in the number of circulating ICOS(+) T cells or N/L ratio during ipilimumab treatment may represent early markers of response. However, given the limited sample size, further investigation is required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Female
  • Humans
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Ipilimumab
  • Lymphocyte Count
  • Male
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Melanoma / mortality*
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Inducible T-Cell Co-Stimulator Protein
  • Ipilimumab