皮肤免疫相关不良事件与接受免疫检查点抑制剂治疗的晚期癌症患者更长的总生存期相关：一项多机构队列研究。

Cutaneous immune-related adverse events are associated with longer overall survival in advanced cancer patients on immune checkpoint inhibitors: a multi-institutional cohort study.

作者信息

Zhang Shijia, Tang Kimberly, Wan Guihong, Nguyen Nga, Lu Chenyue, Ugwu-Dike Pearl, Raval Neel, Seo Jayhyun, Alexander Nora A, Jairath Ruple, Phillipps Jordan, Leung Bonnie W, Roster Kathleen, Chen Wenxin, Zubiri Leyre, Boland Genevieve, Chen Steven T, Tsao Hensin, Demehri Shadmehr, LeBoeuf Nicole R, Reynolds Kerry L, Yu Kun-Hsing, Gusev Alexander, Kwatra Shawn G, Semenov Yevgeniy R

出版信息

medRxiv. 2023 Jan 18:2023.01.16.23284635. doi: 10.1101/2023.01.16.23284635.

DOI:10.1101/2023.01.16.23284635

PMID:36711758

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9882466/

Abstract

BACKGROUND

Cutaneous immune-related adverse events (cirAEs) occur in up to 40% of immune checkpoint inhibitor (ICI) recipients. However, the association of cirAEs with survival remains unclear.

OBJECTIVE

To investigate the association of cirAEs with survival among ICI recipients.

METHODS

ICI recipients were identified from the Mass General Brigham healthcare system (MGB) and Dana-Farber Cancer Institute (DFCI). Patient charts were reviewed for cirAE development within 2 years after ICI initiation. Multivariate time-varying Cox proportional hazards models, adjusted for age, sex, race/ethnicity, Charlson Comorbidity Index, ICI type, cancer type, and year of ICI initiation were utilized to investigate the impact of cirAE development on overall survival.

RESULTS

Of the 3,731 ICI recipients, 18.1% developed a cirAE. 6-month landmark analysis and time-varying Cox proportional hazards models demonstrated that patients who developed cirAEs were associated with decreased mortality (HR=0.87,p=0.027), particularly in melanoma patients (HR=0.67,p=0.003). Among individual morphologies, lichenoid eruption (HR=0.51,p<0.001), psoriasiform eruption (HR=0.52,p=0.005), vitiligo (HR=0.29,p=0.007), isolated pruritus without visible manifestation of rash (HR=0.71,p=0.007), acneiform eruption (HR =0.34,p=0.025), and non-specific rash (HR=0.68, p<0.001) were significantly associated with better survival after multiple comparisons adjustment.

LIMITATIONS

Retrospective design; single geography.

CONCLUSION

CirAE development is associated with improved survival among ICI recipients, especially melanoma patients.

CAPSULE SUMMARY

Patients on immune checkpoint inhibitors (ICIs) who developed cutaneous immune-related adverse events (cirAEs) had favorable outcomes. This was especially notable for melanoma patients who had cirAEs, both those with vitiligo and other morphologies.Development of cirAEs in ICI-treated patients can be used to prognosticate survival and guide treatment decisions.

摘要

背景

高达40%的免疫检查点抑制剂（ICI）接受者会发生皮肤免疫相关不良事件（cirAE）。然而，cirAE与生存率之间的关联仍不清楚。

目的

探讨ICI接受者中cirAE与生存率的关联。

方法

从麻省总医院布莱根医疗系统（MGB）和丹娜法伯癌症研究所（DFCI）中确定ICI接受者。回顾患者病历，以确定ICI开始后2年内cirAE的发生情况。采用多变量时变Cox比例风险模型，并对年龄、性别、种族/民族、查尔森合并症指数、ICI类型、癌症类型和ICI开始年份进行调整，以研究cirAE的发生对总生存期的影响。

结果

在3731名ICI接受者中，18.1%发生了cirAE。6个月的标志性分析和时变Cox比例风险模型表明，发生cirAE的患者死亡率降低（风险比[HR]=0.87，P=0.027），尤其是黑色素瘤患者（HR=0.67，P=0.003）。在个体形态中，苔藓样皮疹（HR=0.51，P<0.001）、银屑病样皮疹（HR=0.52，P=0.005）、白癜风（HR=0.29，P=0.007）、无可见皮疹表现的单纯瘙痒（HR=0.71，P=0.007）、痤疮样皮疹（HR =0.34，P=0.025）和非特异性皮疹（HR=0.68，P<0.001）在多次比较调整后与更好的生存率显著相关。