• Yasuhiro Fujisawa, Koji Yoshino, Atsushi Otsuka, Takeru Funakoshi, Hiroshi Uchi, Taku Fujimura, Shigeto Matsushita, Hiroo Hata, Hisako Okuhira, Ryota Tanaka, Kojiro Nagai, Yoshihiro Ishida, Yoshio Nakamura, Sadanori Furudate, Kentaro Yamamura, Keisuke Imafuku, and Yuki Yamamoto.
• Department of Dermatology, University of Tsukuba, Japan. Electronic address: fujisan@md.tsukuba.ac.jp.
• J. Dermatol. Sci. 2018 Jan 1; 89 (1): 60-66.

BackgroundDue to resistance and immune-related adverse events (irAE) some melanoma patients require ipilimumab after nivolumab therapy. However, little is known about the result of this switching.ObjectiveInvestigate the outcome of ipilimumab switching in Japanese patients.MethodsWe retrospectively collected 60 patients who were treated with ipilimumab after nivolumab from 9 institutes in Japan. Information of the primary tumor, treatment, response, irAE), and survival was collected.ResultsIn our cohort, acral lentiginous and mucosal melanoma accounted for 53% of the cases. The most common reason for initiating ipilimumab was disease progression (93%). Median interval from the last nivolumab administration to first ipilimumab administration was 29days. Only 38% of patients completed 4 injections of ipilimumab. The best overall response was 3.6%. IrAE occurred in 78% of patients and 70% of those were of grade 3/4 (G3/4) and 31% of patients experienced 2 or more irAEs. An within interval of 28days or less between the last nivolumab administration and ipilimumab administration was correlated with the development of G3/4 pyrexia and 3 or more irAEs, but irAE occurrence did not affect survival. Multivariate analysis showed that endocrine irAE (relative risk=0.22, P=0.015) and skin irAE (relative risk=2.78, P=0.048) were significant factors associated with survival.ConclusionIn our study, the response ratio to ipilimumab after nivolumab was unsatisfactory and associated with a high frequency of severe irAEs. As there are few second-line treatment options for patients with BRAF wild-type advanced melanoma after nivolumab failure, patients should be closely monitored if ipilimumab is initiated.Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

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