Lin Jinhe, Li Wenxing, Zhang Xin, Zhou Kai, Yang Yanqi, Cheng Shaoli, Sun Ruifang, Dang Chengxue, Diao Dongmei
Department of Oncology Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Department of Pathology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Thromb Res. 2025 Feb;246:109243. doi: 10.1016/j.thromres.2024.109243. Epub 2024 Dec 22.
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.
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.
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.
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.
免疫检查点抑制剂（ICIs）带来了前所未有的治疗优势，彻底改变了癌症治疗方式。然而，与ICIs相关的血栓栓塞事件（TEEs）风险仍不明确。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中TEEs的发生率。
我们检索了2021年1月至2023年12月期间的随机临床试验（RCTs），不限制癌症类型。系统提取TEEs的百分比。进行了一项NMA，比较阿替利珠单抗、西米普利单抗、度伐利尤单抗、伊匹木单抗、纳武利尤单抗、帕博利珠单抗、传统疗法（主要由化疗、靶向治疗、安慰剂及其组合组成）、两种ICI药物、一种ICI药物与传统疗法联合以及两种ICI药物与传统疗法联合。此外，根据癌症类型进行了亚组分析。
纳入了83项涉及54736名患者的RCTs。接受ICIs的患者发生动脉血栓栓塞（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。与两种ICI药物联合传统疗法相比，纳武利尤单抗（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）发生静脉血栓栓塞（VTE）的风险最低。伊匹木单抗发生肺栓塞（PE）的风险（OR 4.09，95% CI 1.13至15.51）高于纳武利尤单抗。在亚组分析中，对于黑色素瘤，与两种ICI药物相比，纳武利尤单抗显著降低了VTE的风险（OR 0.07，95% CI 0.00至0.76）。在单ICI方案中，度伐利尤单抗与ATE、MI和CVAs的发生率最高相关；伊匹木单抗的VTE和PE发生率最高；帕博利珠单抗的DVT发生率最高。一种ICI药物与传统疗法联合发生TEEs（MI除外）的风险显著高于两种ICI药物联合。
癌症患者中各种ICI方案在TEEs风险方面存在临床上的显著差异。纳武利尤单抗在VTE方面表现出良好的安全性，而伊匹木单抗发生VTE和PE的风险最高。不同的ICI方案需要量身定制的风险管理策略以减少TEEs。
