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帕博利珠单抗致重症肌无力:眼部表现的文献复习及 1 例难治性病例报告

Pembrolizumab-induced Myasthenia Gravis: Literature Review of Ocular Manifestations and a Refractory Case.

机构信息

Capital Coast District Health Board.

Clinical Measurement Unit, Neurology Department.

出版信息

J Immunother. 2022;45(6):267-273. doi: 10.1097/CJI.0000000000000422. Epub 2022 May 17.

Abstract

Immune checkpoint inhibition is a new and promising therapy approved for the treatment of various malignancies. Pembrolizumab is a potent tumor suppressor that acts by upregulating the immune system to recognize cancer cells which may result in disrupted self-tolerance. We describe a case and perform a literature review of myasthenia gravis with ocular manifestations after treatment with pembrolizumab. Our case had bilateral ptosis refractory to conventional treatment, and she remained functionally blind as a result. The literature review included 28 cases of immune-related myasthenia gravis, and a 30% mortality rate excluding deaths from primary cancer progression was shown. Under half had full symptom resolution (n=13, 46%), and there was no clear correlation between specific management strategies and prognosis. Patients with isolated ocular myasthenia gravis (n=9, 32%) were twice as likely to be symptom-free after treatment compared with generalized myasthenia gravis (75% vs. 39%). Respiratory involvement was associated with twice the mortality rate (60% vs. 33%) and triple the risk of noncomplete symptom resolution (20% vs. 61%). The majority of cases had their pembrolizumab discontinued (n=20, 71%), but 3 were successfully rechallenged by utilizing prophylactic low-dose steroids. Patients with immune-related myasthenia gravis experience increased mortality and morbidity but if steroid-responsive, may benefit from the reintroduction of anti-programmed cell death protein 1 therapy for end-stage malignancy with close monitoring. A high index of clinical suspicion for immune-related adverse effects are critical in an era of rising immunotherapy use.

摘要

免疫检查点抑制是一种新的有前途的治疗方法,已被批准用于治疗各种恶性肿瘤。派姆单抗是一种有效的肿瘤抑制剂,通过上调免疫系统来识别癌细胞,从而可能导致自身耐受的破坏。我们描述了一例接受派姆单抗治疗后出现眼肌型重症肌无力的病例,并进行了文献复习。我们的病例有双侧上睑下垂,对常规治疗无效,结果导致她视力严重受损。文献复习包括 28 例免疫相关重症肌无力病例,排除了因原发性癌症进展导致的死亡,死亡率为 30%。只有不到一半的患者症状完全缓解(n=13,46%),特定管理策略与预后之间没有明显的相关性。与全身性重症肌无力(75%比 39%)相比,单纯眼肌型重症肌无力(n=9,32%)患者在治疗后无症状的可能性增加了一倍。有呼吸受累的患者死亡率增加了一倍(60%比 33%),且症状未完全缓解的风险增加了两倍(20%比 61%)。大多数患者停止了派姆单抗治疗(n=20,71%),但 3 例患者通过使用预防性低剂量类固醇成功再次治疗。免疫相关重症肌无力患者的死亡率和发病率增加,但如果对类固醇有反应,可能会受益于重新引入抗程序性细胞死亡蛋白 1 治疗终末期恶性肿瘤,同时密切监测。在免疫治疗日益普及的时代,对免疫相关不良反应的高度临床怀疑至关重要。

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