晚期非小细胞肺癌免疫检查点抑制剂相关性肌炎的临床病理学特征

Clinical and histopathological features of immune checkpoint inhibitor-related myositis in patients with advanced non-small cell lung cancer

目的报道晚期非小细胞肺癌免疫检查点抑制剂(ICI)相关性肌炎的临床病理学特征与治疗转归。方法回顾性分析2019年6月至2020年12月广州医科大学附属第一医院呼吸病理中心数据库的肌肉活检标本及患者的住院病历,纳入7例晚期非小细胞肺癌ICI相关性肌炎,均为男性,中位年龄64岁,年龄范围42~79岁,总结其临床特点。结果7例患者均接受ICI治疗:帕博利珠单抗及信迪利单抗治疗各3例,卡瑞利珠单抗治疗1例。首次用药至发现ICI相关性肌炎的中位时间为45 d,发病时间15~176 d。症状主要表现为肌肉酸痛和四肢乏力,4例患者伴有心肌炎。7例患者均存在肌酸激酶升高,中位值为2354.4 U/L(范围468.6~19709.2 U/L),其中4例出现肌炎相关抗体抗Ro-52抗体阳性。2例患者肌肉活检观察到广泛肌纤维变性坏死和炎症细胞浸润,其他病例只表现为点状肌纤维坏死或非特异性的肌内膜炎症细胞浸润。浸润的炎细胞主要为CD8+T细胞和CD68+的组织细胞。在明确诊断为ICI相关性肌炎后7例患者均立即停用ICI,其中6例患者口服糖皮质激素治疗,7例患者均好转。结论ICI相关性肌炎是一类具有独特的临床病理特征的疾病,部分患者可合并心血管不良反应,如处理不及时可危及生命。及时识别并停用ICI治疗并且采用糖皮质激素治疗可明显改善症状或挽救患者生命。

Objective To investigate the clinicopathologic features and outcome of myositis in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors.Methods The patients diagnosed with immune checkpoint inhibitor-related(ICI)myositis in the database of Respiratory Pathology Center of The First Affiliated Hospital,Guangzhou Medical University from June 2019 to December 2020 were retrospectively analyzed.We reported the muscle histology and main clinical manifestations of the patients in this study.Seven patients with advanced non-small cell lung cancer and ICI related myositis were examined;all of the patients were male,with a median age of 64(range 42-79)years.Results All seven patients developed myositis under therapy(three for pembrolizumab,three for sintilimab,and one for camrelizumab).Median delay between ICI initiation and myositis onset was 45(range 15-176)days.Clinical manifestations were dominated by acute or subacute myalgia and limb weakness.Four patients had evidence of myocarditis.In all of the 7 patients,creatine kinase levels were elevated(median 2354.4,range 468.6-19709.2 U/L),while myositis-associated antibodies Ro-52 were positive in four patients.Muscle biopsy showed evident multifocal necrotic myofibers and infiltration of inflammation in two patients.Other patients only showed non-specific endomysial inflammation.Infiltration of inflammation mainly consisted of CD8+T cells and CD68+histocytes.After the identification of ICI related myositis,ICI treatment was withdrawn in all patients;6 patients received corticosteroids therapy.All patients had shown marked clinical improvement.Conclusions ICI myositis presents with remarkably homogeneous and unique clinicopathologic features,and half of the patients exhibit heightened risk for adverse cardiovascular events,which can be life-threatening if not treated in time.Timely identification of these patients,ICI withdrawal and rapid initiation of corticosteroids therapy can significantly improve patient outcome and/or save patients′lives.