Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma
Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma
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DOI：
10.1093/neuonc/nou001
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发表时间：
2014-04-01
期刊：
影响因子：
15.9
通讯作者：
Tummala, Sudhakar
中科院分区：
文献类型：
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作者：
Liao, Bing;Shroff, Sheetal;Tummala, Sudhakar
Ipilimumab 是 FDA 批准的一种新型重组人单克隆抗体，可阻断细胞毒性 T 淋巴细胞抗原 4，已用于治疗转移性黑色素瘤患者。免疫相关的神经系统不良反应包括炎性肌病、无菌性脑膜炎、可逆性后部脑病综合征、格林-巴尔综合征、重症肌无力综合征、感觉运动神经病和炎性肠神经病。迄今为止，尚无伊匹单抗引起的慢性炎症性脱髓鞘性多发性神经病（CIDP）、横贯性脊髓炎（TM）或并发肌炎和重症肌无力综合征的报道。我们的目标是提高对非典型神经系统不良事件的早期认识并分享我们的治疗方法。我们报告了2012年7月至2013年6月期间在MD安德森癌症中心用ipilimumab治疗的3例转移性黑色素瘤病例，其中患者分别出现CIDP、TM以及并发肌炎和重症肌无力综合征。患者同意出于出版/教育目的发布医疗信息。我们的3例转移性黑色素瘤治疗病例ipilimumab 分别导致 CIDP、TM 以及并发肌炎和重症肌无力综合征。伊匹单抗治疗后至出现免疫相关不良事件的中位时间为 1 至 2 周。由于严重的神经系统症状，伊匹单抗被停用。 CIDP合并肌炎和重症肌无力综合征的患者开始血浆置换术； TM患者接受大剂量静脉注射类固醇，并显示出显着的临床反应。伊匹单抗可引起广泛的神经系统不良反应。我们的研究结果支持停用或停用伊匹单抗的标准治疗。血浆置换或大剂量静脉注射类固醇可被视为治疗严重伊匹单抗相关神经系统不良事件的首选。神经系统症状可能会在 2 周内得到改善。
Ipilimumab is a novel FDA-approved recombinant human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 and has been used to treat patients with metastatic melanoma. Immune-related neurological adverse effects include inflammatory myopathy, aseptic meningitis, posterior reversible encephalopathy syndrome, Guillain-Barr syndrome, myasthenia gravistype syndrome, sensorimotor neuropathy, and inflammatory enteric neuropathy. To date, there is no report for ipilimumab-induced chronic inflammatory demyelinating polyneuropathy (CIDP), transverse myelitis (TM), or concurrent myositis and myasthenia gravistype syndrome. Our objective is to raise early recognition of atypical neurological adverse events and to share our therapeutic approach.We report 3 cases of metastatic melanoma treated with ipilimumab in which the patients developed CIDP, TM, and concurrent myositis and myasthenia gravistype syndrome, respectively, at the MD Anderson Cancer Center between July 2012 and June 2013. Patients consented to release of medical information for publication/educational purposes.Our 3 cases of metastatic melanoma treated with ipilimumab developed CIDP, TM, and concurrent myositis and myasthenia gravistype syndrome, respectively. The median time to onset of immune-related adverse events following ipilimumab treatment ranged from 1 to 2 weeks. Ipilimumab was discontinued due to the severe neurological symptoms. Plasmapheresis was initiated in the patients with CIDP and concurrent myositis and myasthenia gravistype syndrome; high-dose intravenous steroids were given to the patient with TM, and significant clinical response was demonstrated.Ipilimumab could induce a wide spectrum of neurological adverse effects. Our findings support the standard treatment of withholding or discontinuing ipilimumab. Plasmapheresis or high-dose intravenous steroids may be considered as the initial choice of treatment for severe ipilimumab-related neurological adverse events. Improvement of neurological symptoms may be seen within 2 weeks.