免疫抑制剂对晚期黑色素瘤患者免疫检查点抑制剂疗效的影响：一项真实世界、多中心、回顾性研究。

The impact of immunosuppressive agents on immune checkpoint inhibitor efficacy in patients with advanced melanoma: A real-world, multicenter, retrospective study.

作者信息

Lev-Ari Shaked, Serzan Michael, Wu Tianmin, Ip Andrew, Pascual Lauren, Sinclaire Brittany, Adams Shari, Marafelias Michael, Ayyagari Lakshmi, Gill Sarvarinder K, Ma Barbara, Zaemes Jacob P, Della Pia Alexandra, Alaoui Adil, Madhavan Subha, Belouali Anas, Pecora Andrew, Ahn Jaeil, Atkins Michael B, Shah Neil J

机构信息

Department of Oncology, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC, USA.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

出版信息

Cancer. 2023 Jun 15;129(12):1885-1894. doi: 10.1002/cncr.34742. Epub 2023 Mar 23.

DOI:10.1002/cncr.34742

PMID:36951119

Abstract

BACKGROUND

Immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) are often managed via immunosuppressive agents (ISAs); however, their impact on ICI efficacy is not well studied. The impact of the use of ISAs on ICI efficacy in patients with advanced melanoma was therefore investigated.

METHODS

This is a real-world, multicenter, retrospective cohort study of patients with advanced melanoma who received ICIs (n = 370). Overall survival (OS) and time to treatment failure (TTF) from the time of ICI initiation were compared among patients in subgroups of interest by unadjusted and 12-week landmark sensitivity-adjusted analyses. The association of irAEs and their management with OS and TTF were evaluated using univariate and multivariable Cox proportional hazards regression models.

RESULTS

Overall, irAEs of any grade and of grade ≥3 occurred in 57% and 23% of patients, respectively. Thirty-seven percent of patients received steroids, and 3% received other ISAs. Median OS was longest among patients receiving both (not reached [NR]), shorter among those receiving only systemic steroids (SSs) (84.2 months; 95% CI, 40.2 months to NR), and shortest among those who did not experience irAEs (10.3 months; 95% CI, 6-20.1 months) (p < .001). Longer OS was significantly associated with the occurrence of irAEs and the use of SSs with or without ISAs upon multivariable-adjusted analysis (p < .001). Similar results were noted with anti-programmed death 1 (PD-1) monotherapy and combination anti-PD-1 plus anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) therapy, and with 12-week landmark sensitivity analysis (p = .01).

CONCLUSIONS

These findings in patients with melanoma who were treated with ICIs suggest that the use of SSs or ISAs for the management of irAEs is not associated with inferior disease outcomes, which supports the use of these agents when necessary.

摘要

背景

免疫检查点抑制剂（ICI）相关的免疫相关不良事件（irAEs）通常通过免疫抑制药物（ISA）进行管理；然而，其对 ICI 疗效的影响尚未得到充分研究。因此，研究了 ISA 在晚期黑色素瘤患者中的使用对 ICI 疗效的影响。

方法

这是一项真实世界、多中心、回顾性队列研究，纳入了接受 ICI（n=370）治疗的晚期黑色素瘤患者。通过未调整和 12 周时间点敏感性调整分析，比较了感兴趣亚组患者的起始 ICI 时间后的总生存（OS）和治疗失败时间（TTF）。采用单变量和多变量 Cox 比例风险回归模型评估 irAEs 及其管理与 OS 和 TTF 的关系。

结果

总体而言，任何级别和≥3 级的 irAEs 分别发生在 57%和 23%的患者中。37%的患者接受了类固醇治疗，3%的患者接受了其他 ISA 治疗。同时接受 ISA 和 SS 治疗的患者中位 OS 最长（未达到[NR]），仅接受 SS 治疗的患者中位 OS 较短（84.2 个月；95%CI，40.2 个月至 NR），未发生 irAEs 的患者中位 OS 最短（10.3 个月；95%CI，6-20.1 个月）（p<0.001）。多变量调整分析显示，OS 较长与 irAEs 的发生以及 SS 联合或不联合 ISA 的使用显著相关（p<0.001）。在接受抗 PD-1 单药治疗和抗 PD-1 联合 CTLA-4 治疗的患者中，以及在 12 周时间点敏感性分析中，也观察到了类似的结果（p=0.01）。