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PD-1/PD-L1抑制剂单药治疗期间皮肤免疫相关不良事件(irAEs)与多系统irAEs之间的关联。

Association between skin immune-related adverse events (irAEs) and multisystem irAEs during PD-1/PD-L1 inhibitor monotherapy.

作者信息

Yamaguchi Atsushi, Saito Yoshitaka, Narumi Katsuya, Furugen Ayako, Takekuma Yoh, Shinagawa Naofumi, Shimizu Yasushi, Dosaka-Akita Hirotoshi, Sugawara Mitsuru, Kobayashi Masaki

机构信息

Department of Pharmacy, Hokkaido University Hospital, Kita-14-Jo, Nishi-5-Chome, Kita-Ku, Sapporo, 060-8648, Japan.

Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-0812, Japan.

出版信息

J Cancer Res Clin Oncol. 2023 Apr;149(4):1659-1666. doi: 10.1007/s00432-022-04425-z. Epub 2022 Nov 8.

Abstract

PURPOSE

Patients treated with immune checkpoint inhibitors (ICIs) often develop immune-related adverse events (irAEs) in various organs of the body. However, the patient factors associated with the development of multisystem irAEs are not well known. Skin irAEs most frequently occur and appear early after ICI treatment initiation. They may be a predictive marker for the development of multisystem irAEs, and their occurrence should be evaluated.

METHODS

Data of patients receiving ICI monotherapy for lung cancer, melanoma, and head and neck cancer treatment were retrospectively evaluated (n = 207); the single irAE development group (n = 69) was compared with the multisystem irAE development group (n = 37). The primary endpoint was the comparison of the incidence of skin irAEs between the two groups.

RESULTS

Skin, thyroid, and hepatic irAEs were associated with the development of multisystem irAEs (odds ratio: 3.30, 95% confidence interval: 1.27-8.52, p = 0.01 for skin; 5.07, 2.09-12.3, p = 0.0003 for thyroid; 10.63, 1.19-94.7, p = 0.03 for hepatic). Skin irAEs were the most common type (65.0% of total participants) and appeared earlier than other irAEs, except for gastrointestinal and ocular irAEs (median time to onset of skin irAEs: 7.5 weeks). Skin irAEs occurred more frequently in the multisystem irAE group (81.0%) than in the single irAE group (56.5%, p = 0.02).

CONCLUSION

Skin irAEs can be a useful predictive marker for multisystem irAE development due to ICI treatment. Consequently, patients with skin irAEs should be treated and monitored for other types of irAEs.

摘要

目的

接受免疫检查点抑制剂(ICI)治疗的患者身体各器官常出现免疫相关不良事件(irAE)。然而,与多系统irAE发生相关的患者因素尚不明确。皮肤irAE最常出现且在ICI治疗开始后早期出现。它们可能是多系统irAE发生的预测标志物,应对其发生情况进行评估。

方法

回顾性评估接受ICI单药治疗肺癌、黑色素瘤和头颈癌的患者数据(n = 207);将单发irAE发生组(n = 69)与多系统irAE发生组(n = 37)进行比较。主要终点是两组皮肤irAE发生率的比较。

结果

皮肤、甲状腺和肝脏irAE与多系统irAE的发生相关(比值比:皮肤为3.30,95%置信区间:1.27 - 8.52,p = 0.01;甲状腺为5.07,2.09 - 12.3,p = 0.0003;肝脏为10.63,1.19 - 94.7,p = 0.03)。皮肤irAE是最常见类型(占总参与者的65.0%),且除胃肠道和眼部irAE外,比其他irAE出现更早(皮肤irAE的中位发病时间:7.5周)。皮肤irAE在多系统irAE组中的发生率(81.0%)高于单发irAE组(56.5%,p = 0.02)。

结论

皮肤irAE可能是ICI治疗导致多系统irAE发生的有用预测标志物。因此,患有皮肤irAE的患者应接受治疗并监测其他类型的irAE。

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