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[泌尿系统癌症患者免疫检查点抑制剂相关肌炎的临床特征]

[Clinical features of immune checkpoint inhibitor-related myositis in patients with urological cancer].

作者信息

Ying Y C, Tang Q, Yang K W, Mi Y, Fan Y, Yu W, Song Y, He Z S, Zhou L Q, Li X S

机构信息

Department of Urology, Peking University First Hospital; Institute of Urology, Peking University; National Urological Cancer Center, Beijing 100034, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2022 Aug 18;54(4):644-651. doi: 10.19723/j.issn.1671-167X.2022.04.010.

Abstract

OBJECTIVE

Immune checkpoint inhibitors (ICI) have significantly improved the treatment efficacy of a variety of malignant tumors. However, patients may experience a series of special side effects during treatments with ICI. Immune-related myositis after ICI treatment is characterized by autoimmune rheumatic and musculoskeletal damage, which is relatively rare. To analyze the clinical characteristics and outcomes of ICI-associated myositis in urological tumors, we summarized the clinical manifestations, electrophysiological and pathological characteristics, treatments and outcomes in 8 patients.

METHODS

The clinical data of the 8 patients with immune-related myositis after ICI treatment for urological tumors treated in the Department of Urology, Peking University First Hospital from March 2018 to March 2022 were retrospectively analyzed for demographic characteristics, drug regimen, clinical symptoms, laboratory indices, electromyography examination, pathological manifestations and outcomes.

RESULTS

The eight patients included 2 females and 6 males with a median age of 68 years, all treated with ICI for urological neoplasms, including 2 upper tract urothelial carcinoma (UTUC), 3 renal cell carcinoma (RCC), and 3 bladder cancer (BCa). The median time between the first ICI treatment and the detection of immune-related myositis was 39.5 days, and the median duration of treatment was 2 sessions. The main symptoms were muscle pain and weakness, 5 cases with ptosis, 3 cases with secondary rhabdomyolysis, 5 cases with myocarditis, 1 case with myasthenia gravis, and 1 case with enterocolitis. Among them, patients with immune-related myocarditis had a shorter interval from the first anti-programmed cell death protein-1 (PD-1) therapy to the onset of immune-related myositis (=0.042) compared with patients without myocarditis. The 8 patients had significant elevation of transaminases and muscle enzyme profile indexes, and 5 patients showed positive auto-antibodies. 3 patients had perfected muscle biopsies and showed typical skeletal muscle inflammatory myopathy-like pathological changes with CD3, CD4, CD8, CD20 lymphocytes and CD68 macrophage infiltration. After the diagnosis of immune-related myositis, all the 8 patients immediately discontinued ICI therapy and improved after intravenous administration of methylprednisolone alone or in combination with gamma-globulin.

CONCLUSION

Immune-related myositis after ICI treatment is an immune-related adverse reactions (irAEs) with unique clinical and pathological features, commonly combined with cardiovascular adverse reactions. Immediate discontinuation of ICI and initiation of glucocorticoid therapy may improve the patient's condition in a timely manner.

摘要

目的

免疫检查点抑制剂(ICI)显著提高了多种恶性肿瘤的治疗效果。然而,患者在接受ICI治疗期间可能会出现一系列特殊的副作用。ICI治疗后的免疫相关性肌炎以自身免疫性风湿和肌肉骨骼损伤为特征,相对罕见。为分析泌尿系统肿瘤中ICI相关性肌炎的临床特征及转归,我们总结了8例患者的临床表现、电生理和病理特征、治疗方法及转归。

方法

回顾性分析2018年3月至2022年3月在北京大学第一医院泌尿外科接受ICI治疗泌尿系统肿瘤后发生免疫相关性肌炎的8例患者的临床资料,包括人口统计学特征、用药方案、临床症状、实验室指标、肌电图检查、病理表现及转归。

结果

8例患者中,女性2例,男性6例,中位年龄68岁,均接受ICI治疗泌尿系统肿瘤,其中上尿路尿路上皮癌(UTUC)2例,肾细胞癌(RCC)3例,膀胱癌(BCa)3例。首次ICI治疗至免疫相关性肌炎检测的中位时间为39.5天,中位治疗疗程为2个疗程。主要症状为肌肉疼痛和无力,5例有上睑下垂,3例继发横纹肌溶解,5例有心肌炎,1例有重症肌无力,1例有小肠结肠炎。其中,与无心肌炎的患者相比,免疫相关性心肌炎患者从首次抗程序性细胞死亡蛋白1(PD-1)治疗至免疫相关性肌炎发病的间隔时间更短(=0.042)。8例患者转氨酶和肌酶谱指标显著升高,5例患者自身抗体呈阳性。3例患者完善了肌肉活检,显示典型的骨骼肌炎性肌病样病理改变,有CD3、CD4、CD8、CD20淋巴细胞和CD68巨噬细胞浸润。诊断为免疫相关性肌炎后,8例患者均立即停用ICI治疗,单独静脉注射甲泼尼龙或联合γ-球蛋白后病情改善。

结论

ICI治疗后的免疫相关性肌炎是一种具有独特临床和病理特征的免疫相关不良反应(irAEs),常合并心血管不良反应。立即停用ICI并启动糖皮质激素治疗可能及时改善患者病情。

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