Yasuhiro Fujisawa1, Koji Yoshino2, Atsushi Otsuka3, Takeru Funakoshi4, Hiroshi Uchi5, Taku Fujimura6, Shigeto Matsushita7, Hiroo Hata8, Hisako Okuhira9, Ryota Tanaka10, Kojiro Nagai2, Yoshihiro Ishida3, Yoshio Nakamura4, Sadanori Furudate6, Kentaro Yamamura7, Keisuke Imafuku8, Yuki Yamamoto9. 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.
BACKGROUND: Due to resistance and immune-related adverse events (irAE) some melanomapatients 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.
Authors: N N Alrabadi; H M Abushukair; O E Ababneh; S S Syaj; S S Al-Horani; A A Qarqash; O A Darabseh; M M Al-Sous; S R Al-Aomar; Y B Ahmed; R Haddad; F A Al Qarqaz Journal: Clin Transl Oncol Date: 2021-04-20 Impact factor: 3.405