INCIDENCE RATES of cutaneous melanoma are continuing to increase in white populations worldwide.¹ To the contrary, recent figures of melanoma-related mortality show a tendency to level off in many countries.² This apparent discrepancy between incidence and mortality can be explained by the fact that only the incidence rates of "thin" melanomas, associated with a favorable prognosis, are increasing.^3,4 This finding derives, at least in part, from the improvement of early diagnosis of melanoma achieved in past decades.⁵

In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination. This analysis captured the 3-year outcome of MM patients who received ipilimumab combined with fotemustine as first- or second-line treatment. Median overall survival (OS), 3-year survival rates, immune-related (ir) progression-free survival (irPFS), brain PFS, and ir duration of response (irDOR) for the entire population and for patients with brain metastases were assessed. Clinical results were correlated with circulating CD3⁺CD4⁺ICOS⁺CD45RO⁺ or CD45RA⁺ T cells, neutrophil/lymphocyte (N/L) ratios, and tumorBRAF-V600 mutational status. Eighty-six MM patients, including 20 with asymptomatic brain metastases that had been pre-treated with radiotherapy in 7 subjects, were enrolled in the study. With a median follow-up of 39.9 months, median OS and 3-year survival rates were 12.9 months [95% confidence interval (CI) 7.1–18.7 months] and 28.5% for the whole study population, and 12.7 months (95% CI 2.7–22.7 months) and 27.8% for patients with brain metastases, respectively. Long-term ir adverse events consisting of G1 rush and pruritus occurred in 21% of patients. The absolute increase from baseline to week 12 in ‘memory’ but not in ‘naïve’ T cells identified patients with a better survival (P = 0.002). The N/L ratio correlated with a significantly better survival at early time points. BRAF status did not correlate with clinical outcome. Long-term analysis of the NIBIT-M1 trial continues to demonstrate efficacy of ipilimumab combined with fotemustine in MM patients. Fotemustine does not seem to impair the immunologic activity of ipilimumab. 2010-019356-50. NCT01654692.

Purpose: To evaluate the prognostic significance of sentinel node biopsy in the management of stage IB and II melanoma patients, and to evaluate the status of nonsentinel nodes as a “second step key factor” to assess the prognosis of these patients. Patients and Methods: We conducted an analysis of data collected in a prospective database. Results: From February 1994 to June 2005, 1,108 consecutive patients with stage IB and II melanoma were submitted to sentinel node biopsy; 176 patients (15.9%) had occult node metastases. The frequency of positive nodes increased with increasing Breslow's thickness. The largest diameter of metastatic foci and their localization within the lymph node were associated with the risk of nonsentinel node metastases only. The 5-year survival of patients with positive sentinel nodes was 81.4% in patients with one positive node and 39.6% in patients with two positive nodes (P = .056). Multivariate analysis indicated that status of sentinel nodes is a key factor and that sex and Breslow's thickness maintain statistically significant relevance. Ulceration, which was associated with survival when considered as single factor (P < .001) had no impact on survival in the multivariate analysis (P = .10). To evaluate the relevance of metastases to nonsentinel nodes, we identified four groups of patients. Conclusion: Evaluation of the sentinel node is a useful procedure to identify patients to be submitted for complete lymph node dissection. The procedure makes it possible to assess the best prognosis of patients.