Correlation between cutaneous adverse events and prognosis in patients with melanoma treated with nivolumab: A single institutional retrospective study

Treatment for patients with unresectable melanoma has been dramatically changed by the use of immunocheckpoint inhibitors (ICI). In this study, we reviewed patients with unresectable stage III/IV melanoma, who were treated with nivolumab between July 2014 and March 2017 at the Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, and retrospectively recorded cutaneous adverse events (cAE), development of vitiligo, clinical characteristics and clinical responses. We identified 128 patients, 61 (47.7%) of whom showed cAE, including 30 (23.4%) with development or exacerbation of vitiligo. The prognosis of patients with melanoma treated with ICI correlated with cAE, including development of vitiligo. Patients with cAE showed better objective responses (41.0% vs 6.0%, P < 0.001), progression-free survival (PFS) (377 vs 61 days, P < 0.001) and overall survival (OS) (763 vs 209 days, P < 0.001) than did patients without cAE. Patients who developed vitiligo showed better objective responses (53.3% vs 29.0% vs 6.0%, P < 0.001), PFS (median, not reached vs 317 vs 65 days, P < 0.001) and OS (not reached vs 689 vs 209 days, P < 0.001) than did patients with other cAE and patients without cAE. Landmark analysis showed development of vitiligo starting 20 weeks after starting nivolumab correlated with better OS. In multivariate analysis, OS correlated with performance status, number of metastasized organs, cAE other than vitiligo and development of vitiligo. Despite the fact that the correlation between other cAE and OS was less than that of vitiligo, cAE may be a simple marker of favorable prognosis.