Thromboembolic events associated with immune checkpoint inhibitors in cancer patients: A Bayesian network meta-analysis.

IF 3.7 3区医学 Q1 HEMATOLOGY Thrombosis research Pub Date : 2025-02-01 Epub Date: 2024-12-22 DOI:10.1016/j.thromres.2024.109243

Jinhe Lin, Wenxing Li, Xin Zhang, Kai Zhou, Yanqi Yang, Shaoli Cheng, Ruifang Sun, Chengxue Dang, Dongmei Diao

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引用次数: 0

Abstract

Background: Immune checkpoint inhibitors (ICIs), which offer previously unknown therapeutic advantages, have revolutionized cancer treatment. However, the risk of thromboembolic events (TEEs) associated with ICIs remains unclear. The aim of this network meta-analysis (NMA) was to evaluate the incidence of TEEs in cancer patients receiving different treatment regimens.

Methods: We searched for randomized clinical trials (RCTs) between January 2021 and December 2023 without restricting the cancer type. The percentages of TEEs were systematically extracted. An NMA was performed comparing atezolizumab, cemiplimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, conventional therapy (which consists mainly of chemotherapy, targeted therapy, placebo, and their combinations), two ICI drugs, one ICI drug combined with conventional therapy, and two ICI drugs combined with conventional therapy. Additionally, subgroup analysis was conducted based on cancer type.

Results: Eighty-three RCTs involving 54,736 patients were included. Patients receiving ICIs demonstrated comparable risks of arterial thromboembolism (ATE), deep vein thrombosis (DVT), myocardial infarction (MI), and cerebrovascular accidents (CVAs). Nivolumab (OR 0.39, 95 % CI 0.19 to 0.80) and two ICI drugs (OR 0.52, 95 % CI 0.29 to 0.89) had the lowest risk of venous thromboembolism (VTE) compared to two ICI drugs with conventional therapy. The risk of pulmonary embolism (PE) was greater for ipilimumab (OR 4.09, 95 % CI 1.13 to 15.51) than for nivolumab. For melanoma in the subgroup analysis, nivolumab significantly reduced the risk of VTE (OR 0.07, 95 % CI 0.00 to 0.76) compared to two ICI drugs. Among the single-ICI regimens, durvalumab was associated with the highest incidence of ATE, MI, and CVAs; ipilimumab had the highest incidence of VTE and PE; and pembrolizumab had the highest incidence of DVT. The combination of one ICI drug with conventional therapy was associated with a significantly greater risk of TEEs (except for MI) than the combination of two ICI drugs.

Conclusions: Various ICI regimens in cancer patients exhibit clinically significant differences in the risks of TEEs. Nivolumab exhibited a favorable safety profile regarding VTE, while ipilimumab had the highest risk of both VTE and PE. Different ICI regimens require tailored risk management strategies to reduce TEEs.

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癌症患者中与免疫检查点抑制剂相关的血栓栓塞事件：贝叶斯网络荟萃分析。

背景：免疫检查点抑制剂（ICIs）提供了以前未知的治疗优势，已经彻底改变了癌症治疗。然而，与ICIs相关的血栓栓塞事件（tee）的风险仍不清楚。本网络荟萃分析（NMA）的目的是评估接受不同治疗方案的癌症患者tee的发生率。方法：我们检索了2021年1月至2023年12月期间不限制癌症类型的随机临床试验（rct）。系统地提取tee的百分比。对atezolizumab、cemiplimab、durvalumab、ipilimumab、nivolumab、pembrolizumab、常规治疗（主要包括化疗、靶向治疗、安慰剂及其联合治疗）、两种ICI药物、一种ICI药物联合常规治疗和两种ICI药物联合常规治疗进行NMA比较。此外，根据癌症类型进行亚组分析。结果：纳入83项随机对照试验，共54,736例患者。接受ICIs治疗的患者出现动脉血栓栓塞（ATE）、深静脉血栓形成（DVT）、心肌梗死（MI）和脑血管意外（CVAs）的风险相当。纳武单抗（OR 0.39, 95% CI 0.19至0.80）和两种ICI药物（OR 0.52, 95% CI 0.29至0.89）与两种ICI药物联合常规治疗相比，静脉血栓栓塞（VTE）的风险最低。伊匹单抗的肺栓塞（PE）风险高于纳武单抗（OR 4.09, 95% CI 1.13至15.51）。在黑色素瘤亚组分析中，与两种ICI药物相比，nivolumab显著降低了VTE的风险（OR 0.07, 95% CI 0.00至0.76）。在单ici方案中，杜伐单抗与ATE、MI和cva的最高发生率相关；伊匹单抗组VTE和PE发生率最高；而派姆单抗组的DVT发生率最高。一种ICI药物联合常规治疗与tee（心肌梗死除外）的风险显著高于两种ICI药物联合治疗。结论：肿瘤患者不同的ICI方案在tee风险上有显著的临床差异。Nivolumab在VTE方面表现出良好的安全性，而ipilimumab在VTE和PE方面都具有最高的风险。不同的ICI方案需要量身定制的风险管理策略来减少tee。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Thrombosis research 医学-外周血管病

CiteScore

14.60

自引率

4.00%

发文量

364

审稿时长

31 days

期刊介绍： Thrombosis Research is an international journal dedicated to the swift dissemination of new information on thrombosis, hemostasis, and vascular biology, aimed at advancing both science and clinical care. The journal publishes peer-reviewed original research, reviews, editorials, opinions, and critiques, covering both basic and clinical studies. Priority is given to research that promises novel approaches in the diagnosis, therapy, prognosis, and prevention of thrombotic and hemorrhagic diseases.