免疫检查点阻断疗法对伴有或不伴有淋巴结转移的黑色素瘤行转移灶的疗效——一项多中心队列研究。

The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study.

作者信息

Holmberg Carl-Jacob, Ny Lars, Hieken Tina J, Block Matthew S, Carr Michael J, Sondak Vernon K, Örtenwall Christoffer, Katsarelias Dimitrios, Dimitriou Florentia, Menzies Alexander M, Saw Robyn Pm, Rogiers Aljosja, Straker Richard J, Karakousis Giorgos, Applewaite Rona, Pallan Lalit, Han Dale, Vetto John T, Gyorki David E, Tie Emilia Nan, Vitale Maria Grazia, Ascierto Paulo A, Dummer Reinhard, Cohen Jade, Hui Jane Yc, Schachter Jacob, Asher Nethanel, Helgadottir H, Chai Harvey, Kroon Hidde, Coventry Brendon, Rothermel Luke D, Sun James, Carlino Matteo S, Duncan Zoey, Broman Kristy, Weber Jeffrey, Lee Ann Y, Berman Russell S, Teras Jüri, Ollila David W, Long Georgina V, Zager Jonathan S, van Akkooi Alexander, Olofsson Bagge Roger

机构信息

Sahlgrenska Center for Cancer Research, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden; Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.

Sahlgrenska Center for Cancer Research, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.

出版信息

Eur J Cancer. 2022 Jul;169:210-222. doi: 10.1016/j.ejca.2022.03.041. Epub 2022 May 26.

DOI:10.1016/j.ejca.2022.03.041

PMID:35644725

Abstract

PURPOSE

Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics.

METHODS

A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions.

RESULTS

A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively.

CONCLUSION

Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.

摘要

目的

尽管尚无专门针对局限性皮肤转移（ITM）疾病的前瞻性试验的疗效数据，但关于黑色素瘤局限性皮肤转移的指南仍推荐免疫检查点抑制剂（ICI）作为一线治疗选择。本研究旨在基于来自国际转诊诊所的大量患者数据，分析接受ICI治疗的ITM患者的预后。

方法

一项多中心回顾性队列研究，研究对象为2015年1月至2020年12月期间在澳大利亚、欧洲和美国接受治疗的患者，评估ICI治疗有无淋巴结受累（AJCC8 N1c、N2c和N3c）且无远处疾病（M0）的ITM情况。治疗采用PD-1抑制剂（纳武单抗或派姆单抗）和/或CTLA-4抑制剂（伊匹单抗）。根据针对皮肤病变修改后的RECIST标准评估反应。

结果

共纳入来自8个国家21个机构的287例患者。免疫治疗是64例（22%）患者的一线治疗。分别有233例（81%）和23例（8%）患者接受了PD-1或CTLA-4抑制剂单药治疗，而31例（11%）患者接受了两者联合治疗。总缓解率为56%，完全缓解（CR）率为36%，疾病进展（PD）率为32%。中位无进展生存期为10个月（95%CI 7.4-12.6个月），1年、2年和5年无进展生存率分别为48%、33%和18%。中位总生存期未达到，1年、2年和5年总生存率分别为95%、83%和71%。