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免疫相关不良事件对有和无心血管疾病患者的预后影响:一项回顾性研究。

Prognostic impact of immune-related adverse events on patients with and without cardiovascular disease: a retrospective review.

作者信息

Kazama Shingo, Morimoto Ryota, Kimura Yuki, Shibata Naoki, Ozaki Reina, Araki Takashi, Mizutani Takashi, Oishi Hideo, Arao Yoshihito, Kuwayama Tasuku, Hiraiwa Hiroaki, Kondo Toru, Furusawa Kenji, Shimokata Tomoya, Okumura Takahiro, Bando Yasuko K, Ando Yuichi, Murohara Toyoaki

机构信息

Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.

Department of Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan.

出版信息

Cardiooncology. 2021 Jul 6;7(1):26. doi: 10.1186/s40959-021-00112-z.

Abstract

BACKGROUND

The emergence of immune checkpoint inhibitors (ICIs) has brought about a paradigm shift in cancer treatment as the use of these drugs has become more frequent and for a longer duration. As a result of T-cell-mediated inflammation at the programmed cell death-1, programmed death-ligand-1, and cytotoxic T-lymphocyte antigen-4 pathways, immune-related adverse events (irAEs) occur in various organs and can cause a rare but potentially induced cardiotoxicity. Although irAEs are associated with the efficacy of ICI therapy and better prognosis, there is limited information about the correlation between irAEs and cardiotoxicity and whether the benefits of irAEs apply to patients with underlying cardiovascular disease. This study aimed to investigate the association of irAEs and treatment efficacy in patients undergoing ICI therapy with and without a cardiovascular history.

METHODS

We performed a retrospective review of the medical records of 409 consecutive patients who received ICI therapy from September 2014 to October 2019.

RESULTS

Median patient age was 69 years (29.6% were female). The median follow-up period was 278 days. In total, 69 (16.9%) patients had a history of any cardiovascular disease and 14 (3.4%) patients experienced cardiovascular irAEs after ICI administration. The rate of cardiovascular irAEs was higher in patients with prior non-cardiovascular irAEs than without. The prognosis of patients with irAEs ( +) was significantly better than that of the patients without irAEs (P < 0.001); additionally, this tendency did not depend on the presence or absence of a cardiovascular history. Furthermore, the Cox proportional hazards analysis revealed that irAEs were an independent predictor of mortality.

CONCLUSIONS

Although cardiovascular irAEs may be related to prior non-cardiovascular irAEs under ICI therapy, the occurrence of irAEs had a better prognostic impact and this tendency was not affected by cardiovascular history.

摘要

背景

免疫检查点抑制剂(ICI)的出现使癌症治疗发生了范式转变,因为这些药物的使用越来越频繁且持续时间更长。由于在程序性细胞死亡蛋白1、程序性死亡配体1和细胞毒性T淋巴细胞相关抗原4通路处发生T细胞介导的炎症,免疫相关不良事件(irAE)会在各个器官发生,并可能导致一种罕见但可能诱发的心脏毒性。尽管irAE与ICI治疗的疗效及更好的预后相关,但关于irAE与心脏毒性之间的相关性以及irAE的益处是否适用于有潜在心血管疾病的患者的信息有限。本研究旨在调查有或无心血管病史的接受ICI治疗的患者中irAE与治疗疗效之间的关联。

方法

我们对2014年9月至2019年10月连续接受ICI治疗的409例患者的病历进行了回顾性分析。

结果

患者年龄中位数为69岁(29.6%为女性)。中位随访期为278天。共有69例(16.9%)患者有任何心血管疾病史,14例(3.4%)患者在接受ICI治疗后发生了心血管irAE。有既往非心血管irAE的患者发生心血管irAE的比率高于无既往非心血管irAE的患者。有irAE(+)的患者的预后明显好于无irAE的患者(P<0.001);此外,这种趋势并不取决于有无心血管病史。此外,Cox比例风险分析显示irAE是死亡率的独立预测因素。

结论

尽管在ICI治疗下心血管irAE可能与既往非心血管irAE有关,但irAE的发生对预后有更好的影响,且这种趋势不受心血管病史的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/830d/8259377/f90179fdafec/40959_2021_112_Fig1_HTML.jpg

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