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.
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Acknowledgments
This work was supported in part by the Associazione Italiana per la Ricerca sul Cancro, the Italian Ministry of Health, via the Ricerca Finalizzata 2010, and by an investigational grant from Bristol-Myers Squibb. The EAP was sponsored by Bristol-Myers Squibb. Editorial and writing assistance was provided by StemScientific, funded by Bristol-Myers Squibb. The authors would like to thank the patients and investigators who participated in the European EAP.
Conflict of interest
Michele Maio has had an advisory role for and has received honoraria from Bristol-Myers Squibb. All other authors declared that they had no conflict of interest.
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Di Giacomo, A.M., Calabrò, L., Danielli, R. et al. 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 62, 1021–1028 (2013). https://doi.org/10.1007/s00262-013-1418-6
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DOI: https://doi.org/10.1007/s00262-013-1418-6