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帕博利珠单抗治疗转移性骨巨细胞瘤时发生肝毒性和复发性非 ST 段抬高型心肌梗死。

Hepatotoxicity and Recurrent NSTEMI While on Pembrolizumab for Metastatic Giant Cell Bone Tumor.

机构信息

Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut.

Department of Medicine, University of Illinois Chicago, Chicago, Illinois.

出版信息

Am J Med Sci. 2019 Apr;357(4):343-347. doi: 10.1016/j.amjms.2018.11.017. Epub 2018 Nov 29.

Abstract

We present the first reported case showing metastatic giant bone cell tumor being treated successfully with pembrolizumab after failing prior tyrosine kinase inhibitor therapy. Of note, the patient developed multiple systemic effects associated with checkpoint inhibitor use. One year after starting the checkpoint inhibitor (ICI), the patient also developed hepatitis that was confirmed by liver biopsy and pathology to be, in part, due to drug-mediated toxicity similar to prior ICI toxicity cases that have been reported. Additionally, although the patient had vascular risk factors (hypertension, diabetes and smoking), it was notable from a cardiology perspective that the patient developed 2 subsequent non-ST-elevation myocardial infarctions, with rapid progression of stenosis of the left circumflex artery 2 months apart. The first left heart catheterization showing minimal disease of the left circumflex, but 2 months later, presenting with chest pain, a repeat left heart catheterization showed significant stenosis of the left proximal circumflex, raising the possibilities that either ICI can promote plaque rupture and/or accelerated atherosclerosis; both phenomena have been shown to occur in animal models. The patient also developed thyroiditis with subsequent hypothyroidism, now on thyroid replacement from checkpoint inhibitor use. This case demonstrates the multiorgan adverse effects this new antioncologic agent can have and yet also its promising antitumor effects. Awareness of the side effects among primary care doctors and all specialists will be helpful in managing these potential side effects and research will help elucidate ways to prevent the adverse effects.

摘要

我们报告了首例转移性巨大骨细胞瘤病例,该患者在先前的酪氨酸激酶抑制剂治疗失败后,成功接受了帕博利珠单抗治疗。值得注意的是,该患者出现了多种与检查点抑制剂使用相关的全身效应。开始使用检查点抑制剂(ICI)一年后,该患者还出现了肝炎,通过肝活检和病理学证实,部分原因是药物介导的毒性类似于先前报告的 ICI 毒性病例。此外,尽管该患者存在血管危险因素(高血压、糖尿病和吸烟),但从心脏病学的角度来看,值得注意的是,该患者随后发生了 2 次非 ST 段抬高型心肌梗死,左回旋支狭窄在 2 个月内迅速进展。第一次左心导管检查显示左回旋支轻度病变,但 2 个月后,出现胸痛,再次进行左心导管检查显示左回旋支近端显著狭窄,提示 ICI 可能促进斑块破裂和/或加速动脉粥样硬化;这两种现象在动物模型中都有显示。该患者还出现了甲状腺炎,随后出现甲状腺功能减退,现在因使用 ICI 而需要甲状腺素替代治疗。该病例表明,这种新的抗肿瘤药物可能具有多种器官的不良反应,但也具有有前途的抗肿瘤作用。初级保健医生和所有专家对这些潜在副作用的认识将有助于管理这些潜在的副作用,研究将有助于阐明预防不良反应的方法。

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