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免疫检查点抑制剂相关心脏毒性:一项真实世界回顾性分析。

Cardiotoxicity Related to Immune Checkpoint Inhibitors: A Real-World Retrospective Analysis.

作者信息

She Jianqing, Liu Hui, Wu Haoyu, Tuerhongjiang Gulinigaer, Zheng Tao, Bai Ling

机构信息

Cardiovascular Department, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, China.

出版信息

Front Cardiovasc Med. 2022 May 31;9:838488. doi: 10.3389/fcvm.2022.838488. eCollection 2022.

Abstract

BACKGROUND

Cardiotoxicity related to immune checkpoint inhibitors (ICIs) is a rare but potentially lethal. In ICI-associated adverse events, evidence of cardiotoxicity and clinical predictive factors related to ICI is lacking. Here, we aim to assess the incidence and predictive factors of cardiotoxicity related to ICIs in real-world practice.

OBJECTIVE

We retrospectively analyzed consecutive patients who received PD-1 or PD-L1 at the First Affiliated Hospital of Xi'an Jiaotong University. Clinical characteristics and cardiac lesion markers were collected both at baseline and during longitudinal follow-up from the Biobank database. Follow-up CKMB and NT-proBNP levels and ratios were then evaluated.

RESULTS

A total of 2,304 patients with either PD-1 or PDL-1 utilization between August 2018 and April 2021 were collected. The average age was 59.44 ± 11.45 among PD-1 inhibitor utilizer and 58.97 ± 12.16 among PDL-1 inhibitor utilizer. The baseline creatine kinase isoenzyme MB (CKMB) levels were 17 ± 19 U/L in PD-1 inhibitor users and 17 ± 23 U/L in PDL-1 inhibitor users. Majority of patients were male, with advanced stage cancer, and received ICIs as second-line therapy. The longitudinal change of cardiac enzymes and NT-pro BNP were collected. Cardiac lesion as defined by three times increase of CKMB happens in only minority of patients receiving ICIs therapy. It is also identified that increased CKMB happened in PD-1 inhibitor groups, but not PDL-1 inhibitor groups.

CONCLUSION

We evaluated the profile of cardiotoxicities caused by ICIs based on real-world experience. The cardiac lesion markers are generally unaltered, but it appears that the increased CKMB happened in PD-1 inhibitor groups, but not PDL-1 inhibitor groups.

摘要

背景

与免疫检查点抑制剂(ICI)相关的心脏毒性虽罕见但可能致命。在ICI相关不良事件中,缺乏心脏毒性证据及与ICI相关的临床预测因素。在此,我们旨在评估真实世界中与ICI相关的心脏毒性的发生率及预测因素。

目的

我们回顾性分析了西安交通大学第一附属医院连续接受PD-1或PD-L1治疗的患者。从生物样本库数据库收集基线及纵向随访期间的临床特征和心脏损伤标志物。然后评估随访期间的肌酸激酶同工酶MB(CKMB)和N末端脑钠肽前体(NT-proBNP)水平及比值。

结果

共收集了2018年8月至2021年4月间使用PD-1或PD-L1的2304例患者。PD-1抑制剂使用者的平均年龄为59.44±11.45岁,PD-L1抑制剂使用者的平均年龄为58.97±12.16岁。PD-1抑制剂使用者的基线肌酸激酶同工酶MB(CKMB)水平为17±19 U/L,PD-L1抑制剂使用者为17±23 U/L。大多数患者为男性,患有晚期癌症,且接受ICI作为二线治疗。收集了心脏酶和NT-pro BNP的纵向变化。接受ICI治疗的患者中仅有少数出现CKMB升高三倍所定义的心脏损伤。还发现CKMB升高发生在PD-1抑制剂组,而非PD-L1抑制剂组。

结论

我们基于真实世界经验评估了ICI所致心脏毒性的情况。心脏损伤标志物总体未改变,但似乎CKMB升高发生在PD-1抑制剂组,而非PD-L1抑制剂组。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47ae/9193585/cd158157f274/fcvm-09-838488-g0001.jpg

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