Tian Chia-Yi, Ou Yang-Hao, Chang Shih-Liang, Lin Chih-Ming
Department of Neurology, Changhua Christian Hospital, No. 135, Nanxiao Street, Changhua, 500, Taiwan.
Department of Medicinal Botanicals and Health Applications, Da-Yeh University, No.168, University Road, Changhua, Taiwan.
J Med Case Rep. 2021 Apr 30;15(1):244. doi: 10.1186/s13256-021-02722-8.
Pembrolizumab and other immune checkpoint inhibitors are the emerging treatment for selected, high-grade malignancies. However, a small number of patients are unable to tolerate its adverse effects, leading to discontinuation of this potentially life-changing therapy. In this study, we present a case of high-grade urothelial carcinoma patient, who experienced neurocomplications during the first pembrolizumab administration. However, we were able to limit the adverse effect by concomitant use of low-dose oral steroids.
A 75-year-old Taiwanese female with high-grade urothelial carcinoma of the left ureter came to the neurology clinic with complaints of acute onset of bilateral ptosis 16 days after her first infusion of pembrolizumab. It was found that she developed complete bilateral ptosis and limited extraocular muscle movements. Myasthenia gravis-related antibodies and repetitive stimulation test were negative. We diagnosed her with pembrolizumab-induced myasthenia gravis-like disorder and myositis based on clinical symptoms and elevation of muscle enzymes. We commenced methylprednisolone pulse therapy followed by oral steroid therapy with gradual resolution of the symptoms. Three months later, the patient received a second cycle of pembrolizumab with low-dose oral steroids without any complications.
Pembrolizumab exerts its antitumor activity by interfering with the binding of programmed death 1 and its ligand, programmed death ligand 1. As a result, enhanced cytotoxic T cells can recognize tumor cells and induce cellular death. However, neurological complications may be severe and require prompt recognition and treatment. Our case demonstrated that concomitant use of low-dose steroids and pembrolizumab might prevent such complications.
帕博利珠单抗和其他免疫检查点抑制剂是针对特定高级别恶性肿瘤的新兴治疗方法。然而，少数患者无法耐受其不良反应，导致这种可能改变生命的治疗中断。在本研究中，我们报告了一例高级别尿路上皮癌患者，其在首次使用帕博利珠单抗期间出现了神经并发症。然而，我们通过同时使用低剂量口服类固醇能够限制不良反应。
一名75岁的台湾女性，患有左侧输尿管高级别尿路上皮癌，在首次输注帕博利珠单抗16天后因双侧上睑下垂急性发作前来神经科就诊。发现她出现了完全性双侧上睑下垂和眼外肌运动受限。重症肌无力相关抗体和重复刺激试验均为阴性。基于临床症状和肌肉酶升高，我们诊断她为帕博利珠单抗诱导的重症肌无力样疾病和肌炎。我们开始进行甲泼尼龙冲击治疗，随后进行口服类固醇治疗，症状逐渐缓解。三个月后，患者接受了第二个周期的帕博利珠单抗治疗，并同时使用低剂量口服类固醇，未出现任何并发症。
帕博利珠单抗通过干扰程序性死亡1与其配体程序性死亡配体1的结合发挥其抗肿瘤活性。结果，增强的细胞毒性T细胞可以识别肿瘤细胞并诱导细胞死亡。然而，神经并发症可能很严重，需要及时识别和治疗。我们的病例表明，同时使用低剂量类固醇和帕博利珠单抗可能预防此类并发症。
