Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma. 
Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma.  Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research.  Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available.  Patients received ipilimumab 3 mg/kg every 3 weeks for four doses.  Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria.  Patients were monitored continuously for adverse events (AEs), including immune-related AEs.  Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12.  Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %.  With a median follow-up of 24 months, median overall survival was 9.6 months.  Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12).  Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma.  Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required.