泌尿肿瘤免疫检查点抑制剂相关性肌炎的临床特征

目的: 分析泌尿肿瘤免疫检查点抑制剂(immune checkpoint inhibitor, ICI)相关性肌炎的临床特征及治疗转归。方法: 选择2018年3月—2022年3月北京大学第一医院泌尿外科诊治的8例泌尿肿瘤ICI治疗后免疫相关性肌炎患者的临床资料进行回顾性分析,对人口学特征、用药方案、临床症状、实验室指标、肌电图检查、病理表现、治疗转归等信息进行分析。结果: 8例患者包含女性2例、男性6例,中位年龄68岁,均因泌尿肿瘤接受ICI治疗,包括2例上尿路尿路上皮癌(upper tract urothelial carcinoma,UTUC)、3例肾细胞癌(renal cell carcinoma,RCC)和3例膀胱癌(bladder cancer, BCa)。首次ICI治疗至发现免疫相关性肌炎的中位时间为39.5 d,中位疗程为2个疗程。主要症状为肌肉酸痛乏力,5例伴眼睑下垂,3例继发横纹肌溶解,5例合并心肌炎,1例合并重症肌无力,1例合并肠炎。发现合并免疫相关性心肌炎的患者首次接受ICI治疗至肌炎起病的间隔时间更短(P=0.042)。8例患者均有转氨酶及肌酶谱指标显著升高,5例患者出现自身抗体阳性。3例患者完善了肌肉活检,表现出典型的骨骼肌炎性肌病样病理改变,伴CD3⁺、CD4⁺、CD8⁺、CD20⁺淋巴细胞和CD68⁺巨噬细胞浸润。诊断免疫相关性肌炎后8例患者均立即停用ICI治疗,使用甲泼尼龙单独或合并丙种球蛋白静脉注射后病情均好转。结论: ICI治疗后免疫相关性肌炎是具有独特临床及病理特征的免疫相关不良反应(immune-related adverse events, irAEs),常见合并心血管不良反应,立即停用ICI并开始糖皮质激素治疗可以及时改善患者病情。

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

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 (P=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.