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

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, Yuki Yamamoto

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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 29 days. 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 28 days 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.

Original languageEnglish
Pages (from-to)60-66
Number of pages7
JournalJournal of Dermatological Science
Volume89
Issue number1
DOIs
Publication statusPublished - Jan 2018

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Melanoma
Retrospective Studies
Survival
ipilimumab
nivolumab
Disease Progression
Tumors
Skin
Japan
Fever
Therapeutics
Multivariate Analysis
Extremities
Injections
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology

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Retrospective study of advanced melanoma patients treated with ipilimumab after nivolumab : Analysis of 60 Japanese patients. / Fujisawa, Yasuhiro; Yoshino, Koji; Otsuka, Atsushi; Funakoshi, Takeru; Uchi, Hiroshi; Fujimura, Taku; Matsushita, Shigeto; Hata, Hiroo; Okuhira, Hisako; Tanaka, Ryota; Nagai, Kojiro; Ishida, Yoshihiro; Nakamura, Yoshio; Furudate, Sadanori; Yamamura, Kentaro; Imafuku, Keisuke; Yamamoto, Yuki.

In: Journal of Dermatological Science, Vol. 89, No. 1, 01.2018, p. 60-66.

Research output: Contribution to journalArticle

Fujisawa, Y, Yoshino, K, Otsuka, A, Funakoshi, T, Uchi, H, Fujimura, T, Matsushita, S, Hata, H, Okuhira, H, Tanaka, R, Nagai, K, Ishida, Y, Nakamura, Y, Furudate, S, Yamamura, K, Imafuku, K & Yamamoto, Y 2018, 'Retrospective study of advanced melanoma patients treated with ipilimumab after nivolumab: Analysis of 60 Japanese patients', Journal of Dermatological Science, vol. 89, no. 1, pp. 60-66. https://doi.org/10.1016/j.jdermsci.2017.10.009
Fujisawa, Yasuhiro ; Yoshino, Koji ; Otsuka, Atsushi ; Funakoshi, Takeru ; Uchi, Hiroshi ; Fujimura, Taku ; Matsushita, Shigeto ; Hata, Hiroo ; Okuhira, Hisako ; Tanaka, Ryota ; Nagai, Kojiro ; Ishida, Yoshihiro ; Nakamura, Yoshio ; Furudate, Sadanori ; Yamamura, Kentaro ; Imafuku, Keisuke ; Yamamoto, Yuki. / Retrospective study of advanced melanoma patients treated with ipilimumab after nivolumab : Analysis of 60 Japanese patients. In: Journal of Dermatological Science. 2018 ; Vol. 89, No. 1. pp. 60-66.
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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 29 days. 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 28 days 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.",
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AU - Fujisawa, Yasuhiro

AU - Yoshino, Koji

AU - Otsuka, Atsushi

AU - Funakoshi, Takeru

AU - Uchi, Hiroshi

AU - Fujimura, Taku

AU - Matsushita, Shigeto

AU - Hata, Hiroo

AU - Okuhira, Hisako

AU - Tanaka, Ryota

AU - Nagai, Kojiro

AU - Ishida, Yoshihiro

AU - Nakamura, Yoshio

AU - Furudate, Sadanori

AU - Yamamura, Kentaro

AU - Imafuku, Keisuke

AU - Yamamoto, Yuki

PY - 2018/1

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N2 - 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 29 days. 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 28 days 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.

AB - 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 29 days. 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 28 days 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.

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