Department of Dermatology, University of Tsukuba, Japan.
Department of Dermatology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Japan.
J Dermatol Sci. 2018 Jan;89(1):60-66. doi: 10.1016/j.jdermsci.2017.10.009. Epub 2017 Oct 25.
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.
Investigate the outcome of ipilimumab switching in Japanese patients.
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.
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.
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.
由于耐药性和免疫相关不良事件（irAE），一些黑色素瘤患者在接受纳武利尤单抗治疗后需要使用伊匹单抗。然而，对于这种转换的结果知之甚少。
研究日本患者中伊匹单抗转换的结果。
我们回顾性收集了来自日本 9 家机构的 60 名接受纳武利尤单抗治疗后使用伊匹单抗的患者。收集了原发肿瘤、治疗、反应、irAE）和生存信息。
在我们的队列中，肢端黑色素瘤和黏膜黑色素瘤占病例的 53%。开始使用伊匹单抗的最常见原因是疾病进展（93%）。末次纳武利尤单抗给药至首次伊匹单抗给药的中位间隔为 29 天。只有 38%的患者完成了 4 次伊匹单抗注射。最佳总缓解率为 3.6%。irAE 发生在 78%的患者中，70%为 3/4 级（G3/4），31%的患者发生 2 次或以上 irAE。末次纳武利尤单抗给药与伊匹单抗给药之间间隔 28 天或更短与 G3/4 发热和 3 次或更多 irAE 的发生相关，但 irAE 的发生并不影响生存。多变量分析显示，内分泌 irAE（相对风险=0.22，P=0.015）和皮肤 irAE（相对风险=2.78，P=0.048）是与生存相关的显著因素。
在我们的研究中，纳武利尤单抗后使用伊匹单抗的反应率不理想，且与严重 irAE 的发生率高相关。由于纳武利尤单抗治疗失败后 BRAF 野生型晚期黑色素瘤患者的二线治疗选择很少，如果开始使用伊匹单抗，应密切监测患者。
