Cancer Immunology, Immunotherapy

, Volume 62, Issue 6, pp 1021–1028

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

  • Anna Maria Di Giacomo
  • Luana Calabrò
  • Riccardo Danielli
  • Ester Fonsatti
  • Erica Bertocci
  • Isabella Pesce
  • Carolina Fazio
  • Ornella Cutaia
  • Diana Giannarelli
  • Clelia Miracco
  • Maurizio Biagioli
  • Maresa Altomonte
  • Michele Maio
Original Article

DOI: 10.1007/s00262-013-1418-6

Cite this article as:
Di Giacomo, A.M., Calabrò, L., Danielli, R. et al. Cancer Immunol Immunother (2013) 62: 1021. doi:10.1007/s00262-013-1418-6

Abstract

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.

Keywords

BiomarkerExpanded access programmeIpilimumabLong-term survivalMetastatic melanoma

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Anna Maria Di Giacomo
    • 1
  • Luana Calabrò
    • 1
  • Riccardo Danielli
    • 1
  • Ester Fonsatti
    • 1
  • Erica Bertocci
    • 1
  • Isabella Pesce
    • 1
  • Carolina Fazio
    • 1
  • Ornella Cutaia
    • 1
  • Diana Giannarelli
    • 2
  • Clelia Miracco
    • 3
  • Maurizio Biagioli
    • 4
  • Maresa Altomonte
    • 1
  • Michele Maio
    • 1
  1. 1.Division of Medical Oncology and Immunotherapy, Department of Oncology, Istituto Toscano TumoriUniversity Hospital of SienaSienaItaly
  2. 2.Statistical UnitRegina Elena National Cancer InstituteRomeItaly
  3. 3.Department of PathologyUniversity Hospital of SienaSienaItaly
  4. 4.Department of DermatologyUniversity Hospital of SienaSienaItaly