Ipilimumab improves survival in patients with advanced melanoma.,The activity and safety of ipilimumab outside of a clinical trial was assessed in an expanded access programme (EAP).,Ipilimumab was available upon physician request for patients aged 16 or over with pretreated stage III (unresectable)/IV melanoma, for whom no other therapeutic option was available.,Patients received ipilimumab 3 mg/kg every 3 weeks for four doses.,Patients with stable disease or an objective response to ipilimumab were eligible for retreatment upon disease progression.,Tumour assessments were conducted at baseline and week 12.,Patients were monitored for adverse events (AEs) within 3 to 4 days of each scheduled visit.,Of 855 patients participating in the EAP in Italy, 833 were evaluable for response.,Of these, 13% had an objective immune response, and the immune-related disease control rate was 34%.,Median progression-free survival and overall survival were 3.7 and 7.2 months, respectively.,Efficacy was independent of BRAF and NRAS mutational status.,Overall, 33% of patients reported an immune-related AE (irAE).,The frequency of irAEs was not associated with response to ipilimumab.,Outside of a clinical trial setting, ipilimumab is a feasible treatment option in patients with pretreated metastatic melanoma, regardless of BRAF and NRAS mutational status.,Data from this large cohort of patients support clinical trial evidence that ipilimumab can induce durable disease control and long-term survival in patients who have failed to respond to prior treatment.
Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear.,Here we use a mammalian model to investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses.,We show that melanoma induction by ultraviolet A (320-400 nm) requires the presence of melanin pigment and is associated with oxidative DNA damage within melanocytes.,In contrast, ultraviolet B radiation (280-320 nm) initiates melanoma in a pigment-independent manner associated with direct ultraviolet B DNA damage.,Thus, we identified two ultraviolet wavelength-dependent pathways for the induction of CMM and describe an unexpected and significant role for melanin within the melanocyte in melanomagenesis.,Exposure to ultraviolet light is responsible for a large proportion of melanomas but the molecular mechanisms are unknown.,In this study, melanoma is found to be induced in mice by UVA and UVB light in a pigment-dependent and -independent manner, respectively, resulting in different types of DNA damage.