Thromboembolism in Patients with Metastatic Urothelial Cancer Treated with Immune Checkpoint Inhibitors.
Thromboembolism in Patients with Metastatic Urothelial Cancer Treated with Immune Checkpoint Inhibitors.
复制标题
使用免疫检查点抑制剂治疗的转移性尿路上皮癌患者的血栓栓塞。
DOI：
10.1007/s11523-022-00905-x
复制
发表时间：
2022
影响因子：
5.4
通讯作者：
Khorana,AlokA
中科院分区：
文献类型：
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作者：
Sheng,IrisY;Gupta,Shilpa;Reddy,ChandanaA;Angelini,Dana;Funchain,Pauline;Sussman,TamaraA;Sleiman,Joseph;Ornstein,MosheC;McCrae,Keith;Khorana,AlokA
背景免疫治疗已成为转移性尿路上皮癌治疗的主要手段之一。目前尚不清楚免疫检查点抑制剂治疗是否会增加血栓栓塞症(TE)的风险。目的研究在接受免疫检查点抑制剂治疗的转移性尿路上皮癌患者中，动脉血栓栓塞症(ATE)和静脉血栓栓塞症(VTE)事件的发生率及其相关转归。Kaplan-Meier方法评估总体生存率，Cox比例风险回归评估TE对总体生存率的影响。结果在279名患者中，72%的男性(62%)为纯尿路上皮癌患者，他们开始使用阿替唑单抗(40%)、尼伏卢单抗(3%)或培布罗单抗(57%)。平均随访5.6个月(0.3~51.6个月)，42例患者发生TE(VTEn=37，13%，ATEN=5，2%)。免疫检查点抑制剂治疗后6个月和12个月的TE累积发生率分别为9.1%(95%可信区间6.0~13.0)和13.6%(95%可信区间9.6~18.4)。大多数TE(VTE 62%，ATE 100%)发生在免疫检查点抑制剂启动后6个月内(中位数为5，范围1-59)，大多数(VTE 81%，ATE 100%)导致住院(中位数分别为5天和4天)。血栓栓塞症(危险比2.296，p=0.0004)、Bajorin评分1或2(危险比1.490，p=0.0315)和Bajorin评分2(危险比3.5，p<；0.0001)与较差的总体生存相关。血栓栓塞症与存活率恶化以及其他不良结局有关。需要进一步研究免疫检查点抑制因子相关TE的机制。
BackgroundImmunotherapy has become one of the mainstays for metastatic urothelial carcinoma treatment. Whether immune checkpoint inhibitor therapy increases thromboembolism (TE) risk is unknown.ObjectiveWe investigated the incidence of arterial thromboembolism (ATE) and venous thromboembolism (VTE) events and its associated outcomes in patients with metastatic urothelial cancer treated with immune checkpoint inhibitors.MethodsPatients with urothelial cancer treated with immune checkpoint inhibitors at the Cleveland Clinic from 1/1/2015 to 12/31/2019 were identified. The Kaplan–Meier method estimated overall survival and Cox proportional hazards regression evaluated the impact of TE on overall survival.ResultsOf 279 patients, 72% were men with pure urothelial cancer (62%) who started atezolizumab (40%), nivolumab (3%), or pembrolizumab (57%). At a median follow-up of 5.6 months (range 0.3–51.6), 42 patients developed a TE (VTEn= 37, 13%, ATEn= 5, 2%). The cumulative incidence of TE after immune checkpoint inhibitor therapy was 9.1% (95% confidence interval 6.0–13.0) at 6 months and 13.6% (95% confidence interval 9.6–18.4) at 12 months. Most TE (VTE 62%, ATE 100%) occurred within 6 months of immune checkpoint inhibitor initiation (median doses 5, range 1–59), and the majority (VTE 81%, ATE 100%) resulted in hospitalization (median: 5 days, 4 days, respectively). Thromboembolism (hazard ratio 2.296,p= 0.0004), Bajorin score 1 or 2 (hazard ratio 1.490,p= 0.0315), and Bajorin score 2 (hazard ratio 3.50,p< 0.0001) were associated with worse overall survival.ConclusionsImmune checkpoint inhibitors are associated with a high TE risk. Thromboembolism is associated with worsened survival, among other poor outcomes. Further investigation into the mechanism behind immune checkpoint inhibitor-associated TE is needed.