Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies
Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies
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DOI：
10.1212/wnl.0000000000008091
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发表时间：
2019-09-10
期刊：
影响因子：
9.9
通讯作者：
Guidon, Amanda C.
中科院分区：
文献类型：
--
作者：
Dubey, Divyanshu;David, William S.;Guidon, Amanda C.
目的描述与免疫检查点抑制剂（ICIs）相关的神经病变的谱、临床过程和治疗。方法对ci相关性神经病变（irNeuropathy）患者进行诊断，并将其临床特征与细胞毒性神经病变进行比较。结果19例非神经性病变患者。ici包括反程序性死亡-1 (PD1), 9；抗细胞毒性t淋巴细胞相关抗原-4 (CTLA4), 2；抗ctla4和抗pd1,8的组合。神经病变发病前ICI剂量的中位数为4。ICI治疗后神经病变发生率为0.7%。潜在的恶性肿瘤包括黑色素瘤（n = 15）、肺腺癌（n = 3）和胆管癌（n = 1）。神经病变表型为伴或不伴脑膜炎的颅神经病变（n = 7），伴或不伴颅神经受累的非长度依赖性多根神经病变（n = 6），小纤维/自主神经病变（n = 2）， anca相关的多发性单神经炎（n = 1），感觉神经病变（n = 1），长度依赖性感觉运动轴索多神经病变（n = 1）和神经痛性肌萎缩（n = 1）。涉及其他器官系统的免疫相关不良事件很常见（58%）。使用皮质类固醇治疗神经病变与改良兰金量表中位评分（1比0，p = 0.001）和炎性神经病变病因与治疗致残评分（2比0.5,p = 0.012） （IV类）的改善相关。与化疗引起的中毒性神经病相比，急性或亚急性和非长度依赖性表现的irNeuropathy的比例明显更高（p < 0.001），并且irNeuropathy的住院率也更高（p = 0.002）。结论神经病变是一种罕见的免疫抑制并发症。认识到其广泛的表型谱和独特的临床特征，并及时使用皮质类固醇治疗可能会导致良好的结果。
ObjectiveTo describe the spectrum, clinical course, and management of neuropathies associated with immune checkpoint inhibitors (ICIs).MethodsPatients with ICI-related neuropathy (irNeuropathy) were identified and their clinical characteristics compared to neuropathy attributed to cytotoxic agents.ResultsWe identified 19 patients with irNeuropathies. ICIs included anti-programmed death-1 (PD1), 9; anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), 2; and combination of anti-CTLA4 and anti-PD1, 8. Median number of ICI doses prior to neuropathy onset was 4. Rate of neuropathies following ICI therapy was 0.7%. Underlying malignancies included melanoma (n = 15), lung adenocarcinoma (n = 3), and cholangiocarcinoma (n = 1). Neuropathy phenotypes were cranial neuropathies with or without meningitis (n = 7), nonlength-dependent poly-radiculoneuropathies with and without cranial nerve involvement (n = 6), small-fiber/autonomic neuropathy (n = 2), ANCA-associated mononeuritis multiplex (n = 1), sensory neuronopathy (n = 1), length-dependent sensorimotor axonal polyneuropathy (n = 1), and neuralgic amyotrophy (n = 1). Immune-related adverse events involving other organ systems were common (58%). Corticosteroid use for management of neuropathy was associated with improvement in median modified Rankin Scale score (1 vs 0, p = 0.001) and Inflammatory Neuropathy Cause and Treatment Disability score (2 vs 0.5, p = 0.012) (Class IV). Significantly higher proportion of irNeuropathies had acute or subacute and nonlength-dependent presentations (p < 0.001) and rate of hospitalization for irNeuropathy was also higher (p = 0.002) compared to toxic neuropathy from chemotherapy.ConclusionNeuropathy is a rare complication of ICIs that often responds to immunosuppression. Recognition of its wide phenotypic spectrum and distinct clinical characteristics and prompt management with corticosteroids may lead to favorable outcomes.