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J Dermatol Sci. 2018 Jan;89(1):60-66. doi: 10.1016/j.jdermsci.2017.10.009. Epub 2017 Oct 25.

Retrospective study of advanced melanoma patients treated with ipilimumab after nivolumab: Analysis of 60 Japanese patients.

Author information

1
Department of Dermatology, University of Tsukuba, Japan. Electronic address: fujisan@md.tsukuba.ac.jp.
2
Department of Dermatology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Japan.
3
Department of Dermatology, Kyoto University Graduate School of Medicine, Japan.
4
Department of Dermatology, Keio University School of Medicine, Japan.
5
Department of Dermatology, University of Kyushu, Japan.
6
Department of Dermatology, Tohoku University Graduate School of Medicine, Japan.
7
Department of Dermato-Oncology/Dermatology, National Hospital Organization Kagoshima Medical Center, Japan.
8
Department of Dermatology, University of Hokkaido, Japan.
9
Department of Dermatology, Wakayama Medical University, Japan.
10
Department of Dermatology, University of Tsukuba, Japan.

Abstract

BACKGROUND:

Due 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.

OBJECTIVE:

Investigate the outcome of ipilimumab switching in Japanese patients.

METHODS:

We 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.

RESULTS:

In 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.

CONCLUSION:

In 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.

KEYWORDS:

Checkpoint inhibitor; Ipilimumab; Melanoma; Nivolumab; Switching

PMID:
29079332
DOI:
10.1016/j.jdermsci.2017.10.009
[Indexed for MEDLINE]

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