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免疫检查点抑制剂治疗后与眼部不良事件相关的因素。

Factors associated with ocular adverse event after immune checkpoint inhibitor treatment.

机构信息

Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Yonsei-ro 50-1, Seodaemun-gu, Seoul, Republic of Korea.

Department of Ophthalmology, Konyang University College of Medicine, Daejeon, Republic of Korea.

出版信息

Cancer Immunol Immunother. 2020 Dec;69(12):2441-2452. doi: 10.1007/s00262-020-02635-3. Epub 2020 Jun 17.

Abstract

Ocular adverse events (OAEs) including vision-threatening intraocular inflammation after immune checkpoint inhibitor (ICI) treatment have been increasingly reported; however, the risk factors associated with OAEs remain elusive. Here, we determined the factors associated with OAEs after ICI treatment. We analyzed 40 consecutive patients who experienced OAEs after ICI treatments. The OAEs included anterior uveitis, chorioretinitis, papillitis, foveal interdigitation zone thickening/serous retinal detachment (IZT/SRD), retinal vascular occlusion, and strabismus and ptosis. Of 40 patients, 18 (45%) were treated with atezolizumab, 13 (33%) with pembrolizumab, 7 (18%) with nivolumab, 1 (3%) with ipilimumab/nivolumab, and the other 1 (3%) with durvalumab/tremelimumab. BRAF/MEK inhibitors were concurrently used in 19 (48%) patients. Occurrence of intraocular inflammation was significantly associated with previous ocular surgery and trauma history (P = 0.015) and pembrolizumab use (P = 0.031). Neuro-ophthalmic complications and IZT/SRD were associated with brain metastasis (P = 0.005) and treatment with BRAF/MEK inhibitor (P < 0.001), respectively. In extensive literature review for clinical cases, we identified seven cases with intraocular inflammation, which were not observed with ipilimumab treatment, that occurred after a change of the drug to pembrolizumab. Collectively, these findings provide better understandings of OAEs after ICI treatment.

摘要

眼部不良反应(OAEs)包括免疫检查点抑制剂(ICI)治疗后威胁视力的眼内炎症,越来越多的报道;然而,与 OAEs 相关的危险因素仍不清楚。在这里,我们确定了 ICI 治疗后与 OAEs 相关的因素。我们分析了 40 例连续接受 ICI 治疗后发生 OAEs 的患者。OAEs 包括前葡萄膜炎、脉络膜炎、视乳头炎、黄斑区交织增厚/浆液性视网膜脱离(IZT/SRD)、视网膜血管闭塞和斜视及上睑下垂。40 例患者中,18 例(45%)接受阿替利珠单抗治疗,13 例(33%)接受帕博利珠单抗治疗,7 例(18%)接受纳武利尤单抗治疗,1 例(3%)接受伊匹单抗/纳武利尤单抗治疗,另 1 例(3%)接受度伐鲁单抗/替西木单抗治疗。19 例(48%)患者同时使用 BRAF/MEK 抑制剂。眼内炎症的发生与既往眼部手术和外伤史(P=0.015)和帕博利珠单抗使用(P=0.031)显著相关。神经眼科并发症和 IZT/SRD 与脑转移(P=0.005)和 BRAF/MEK 抑制剂治疗(P<0.001)相关。在对临床病例的广泛文献回顾中,我们发现了 7 例在药物更换为帕博利珠单抗后发生的、未观察到伊匹单抗治疗的眼内炎症病例。这些发现共同提供了对 ICI 治疗后 OAEs 的更好理解。

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