Sussman Tamara A, Giobbie-Hurder Anita, Dryg Ian D, Manos Michael, Weirather Jason L, LeBoeuf Nicole R, Hodi F Stephen, Connors Jean M
Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
J Immunother Cancer. 2025 May 7;13(5):e010761. doi: 10.1136/jitc-2024-010761.
The relationship between venous thromboembolism (VTE) and immune checkpoint inhibitor therapy (ICI) is unclear. This analysis investigates the incidence of and risk factors for VTE in VTE-naive patients with cancer receiving ICI treatment.
A retrospective cohort study of patients receiving any type or combination of ICI from 2009 to 2022 at Dana-Farber Cancer Institute was conducted to identify VTE occurring after initiation of ICI treatment. Cumulative incidences of VTE were determined using Fine and Gray's methods. Associations between VTE, ICI regimens, and clinical risk factors were evaluated using propensity-score stratified, multivariable Cox proportional hazards models.
In 10,638 patients without a prior history of VTE, the 6-month cumulative incidence of VTE was 7.6% (95% CI: 7.1% to 8.1%) and 11.1% (95% CI: 10.5% to 11.8%) at 12 months. Clinical risk factors included: age 15-59 (HR 1.27; 95% CI: 1.12 to 1.43; p=0.002), obesity (HR: 1.41; 95% CI: 1.16 to 1.71) and history of anticoagulation prior to ICI start (HR: 1.43; 95% CI: 1.26 to 1.61). Compared with pembrolizumab, treatment with ipilimumab/nivolumab increased the risk of VTE (HR: 1.36; 95% CI: 1.02 to 1.82), while durvalumab conveyed lower risk (HR: 0.52; 95% CI: 0.31 to 0.87). Treatment with programmed cell death ligand 1 had significantly reduced risk of VTE (HR: 0.79; 95% CI: 0.63 to 0.99) compared with programmed cell death 1 monotherapy. Dual ICI blockade with cytotoxic T lymphocyte antigen 4/PD-1 significantly increased the risk of VTE (HR: 1.43; 95% CI 1.12 to 1.84). Initiation of anticoagulation after starting ICI for indications other than VTE reduced the risk by 40% (HR: 0.60, 95% CI: 0.48 to 0.73).
ICI treatment appears to be independently associated with a high incidence of VTE in patients with cancer warranting further investigation.
静脉血栓栓塞症（VTE）与免疫检查点抑制剂疗法（ICI）之间的关系尚不清楚。本分析调查了接受ICI治疗的初发VTE癌症患者中VTE的发生率及危险因素。
对2009年至2022年在丹娜-法伯癌症研究所接受任何类型或组合ICI治疗的患者进行回顾性队列研究，以确定ICI治疗开始后发生的VTE。使用Fine和Gray方法确定VTE的累积发生率。使用倾向评分分层多变量Cox比例风险模型评估VTE、ICI方案和临床危险因素之间的关联。
在10638例无VTE既往史的患者中，VTE的6个月累积发生率为7.6%（95%CI：7.1%至8.1%），12个月时为11.1%（95%CI：10.5%至11.8%）。临床危险因素包括：年龄15 - 59岁（HR 1.27；95%CI：1.12至1.43；p = 0.002）、肥胖（HR：1.41；95%CI：1.16至1.71）以及ICI开始前的抗凝史（HR：1.43；95%CI：1.26至1.61）。与帕博利珠单抗相比，伊匹木单抗/纳武利尤单抗治疗增加了VTE风险（HR：1.36；95%CI：1.02至1.82），而度伐利尤单抗的风险较低（HR：0.52；95%CI：0.31至0.87）。与程序性死亡蛋白1（PD - 1）单药治疗相比，程序性死亡配体1（PD - L1）治疗显著降低了VTE风险（HR：0.79；95%CI：0.63至0.99）。细胞毒性T淋巴细胞相关抗原4/PD - 1双重ICI阻断显著增加了VTE风险（HR：1.43；95%CI 1.12至1.84）。在因VTE以外的适应症开始ICI治疗后开始抗凝可使风险降低40%（HR：0.60，95%CI：0.48至0.73）。
ICI治疗似乎与癌症患者中VTE的高发生率独立相关，值得进一步研究。
