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皮肤免疫相关不良反应与接受免疫检查点抑制剂治疗的晚期癌症患者的总生存期延长相关: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.

机构信息

Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts.

Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

出版信息

J Am Acad Dermatol. 2023 May;88(5):1024-1032. doi: 10.1016/j.jaad.2022.12.048. Epub 2023 Feb 2.

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 and Dana-Farber Cancer Institute. 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 3731 ICI recipients, 18.1% developed a cirAE. Six-month landmark analysis and time-varying Cox proportional hazards models demonstrated that patients who developed cirAEs were associated with decreased mortality (hazardratio [HR] = 0.87, P = .027), particularly in patients with melanoma (HR = 0.67, P = .003). Among individual morphologies, lichenoid eruption (HR = 0.51, P < .001), psoriasiform eruption (HR = 0.52, P = .005), vitiligo (HR = 0.29, P = .007), isolated pruritus without visible manifestation of rash (HR = 0.71, P = .007), acneiform eruption (HR = 0.34, P = .025), and non-specific rash (HR = 0.68, P < .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 patients with melanoma.

摘要

背景

多达 40%的免疫检查点抑制剂(ICI)受者会出现皮肤免疫相关不良事件(cirAEs)。然而,cirAEs 与生存的关联尚不清楚。

目的

研究 cirAEs 与 ICI 受者生存的关系。

方法

从马萨诸塞州综合医院和丹娜-法伯癌症研究所的医疗系统中确定 ICI 受者。在 ICI 开始后 2 年内,通过患者病历回顾评估 cirAE 的发生情况。利用多变量时变 Cox 比例风险模型,调整年龄、性别、种族/民族、Charlson 合并症指数、ICI 类型、癌症类型和 ICI 开始年份,研究 cirAE 发生对总生存的影响。

结果

在 3731 名 ICI 受者中,18.1%发生 cirAE。6 个月的时间节点分析和时变 Cox 比例风险模型表明,发生 cirAEs 的患者死亡率降低(风险比[HR] = 0.87,P = 0.027),特别是黑色素瘤患者(HR = 0.67,P = 0.003)。在各个形态中,苔藓样疹(HR = 0.51,P < 0.001)、银屑病样疹(HR = 0.52,P = 0.005)、白癜风(HR = 0.29,P = 0.007)、孤立性瘙痒而无皮疹可见表现(HR = 0.71,P = 0.007)、痤疮样疹(HR = 0.34,P = 0.025)和非特异性皮疹(HR = 0.68,P < 0.001)与调整后的多重比较后生存改善显著相关。

局限性

回顾性设计;单一地理位置。

结论

cirAE 的发生与 ICI 受者的生存改善相关,特别是黑色素瘤患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a73d/10283025/5afc29ff136c/nihms-1902791-f0001.jpg

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