Department of Neurology, Mayo Clinic, Rochester, MN.
J Immunother. 2018 May;41(4):208-211. doi: 10.1097/CJI.0000000000000196.
Programmed death-1 (PD-1) inhibitors are increasingly used in cancer immunotherapy. Various immune-related adverse events are reported, including infrequent individual case reports of myositis or rhabdomyolysis. The frequency and diagnostic spectrum of immune-related adverse events affecting skeletal muscle in PD-1 inhibitor-treated patients are unknown. We searched the Mayo Clinic Pharmacy database (2014-2016) to identify patients who developed myopathies during or after PD-1 inhibitor therapy. Among 654 cancer patients received PD-1 inhibitors (pembrolizumab=389; nivolumab=264; both=1), we identified 5 patients (pembrolizumab=5) with biopsy-proven myopathies (2 necrotizing myopathy, 1 early dermatomyositis, and 2 nonspecific myopathy). Four patients developed concomitant autoimmune disorders. Weakness occurred after a median of 2 treatments (range, 1-4). All patients had proximal or axial weakness. Four patients had either bulbar or extraocular weakness, but only 1 patient had acetylcholine receptor antibodies. Creatine kinase levels were elevated in 3 patients (necrotizing myopathy=2; nonspecific myopathy=1). Brain magnetic resonance imaging revealed abnormal T2 signal and enhancement of extraocular muscles in 1 patient with ophthalmoparesis. Pembrolizumab was discontinued in all patients. All patients received immunosuppressive therapy, with fatal outcome in 2 necrotizing myopathy patients and favorable outcome in others. We conclude that myopathy is a rare, but unique complication of PD-1 inhibitors with frequent involvement of extraocular or bulbar muscles, mimicking myasthenia gravis. Muscle biopsy is an important test for PD-1 inhibitor-treated patients who develop oculobulbar weakness and hyperCKemia, to distinguish patients with necrotizing myopathy from myasthenia gravis. Necrotizing myopathy patients may require more aggressive immunotherapy due to their grave prognosis.
程序性死亡受体-1（PD-1）抑制剂在癌症免疫治疗中的应用越来越广泛。各种免疫相关不良反应均有报道，包括肌炎或横纹肌溶解症的罕见个别病例报告。PD-1 抑制剂治疗患者中影响骨骼肌的免疫相关不良反应的频率和诊断谱尚不清楚。我们检索了梅奥诊所药房数据库（2014-2016 年），以确定在 PD-1 抑制剂治疗期间或之后发生肌病的患者。在接受 PD-1 抑制剂（派姆单抗=389；纳武单抗=264；两者均=1）治疗的 654 例癌症患者中，我们发现 5 例（派姆单抗=5 例）患者存在活检证实的肌病（2 例坏死性肌病，1 例早期皮肌炎，2 例非特异性肌病）。4 例患者同时发生自身免疫性疾病。中位时间为 2 次治疗后（范围，1-4 次）出现无力。所有患者均有近端或轴性无力。4 例患者有球部或眼外肌无力，但仅有 1 例患者有乙酰胆碱受体抗体。3 例患者的肌酸激酶水平升高（坏死性肌病=2；非特异性肌病=1）。1 例眼肌麻痹患者的脑磁共振成像显示眼外肌异常 T2 信号和增强。所有患者均停用派姆单抗。所有患者均接受免疫抑制治疗，2 例坏死性肌病患者死亡，其他患者预后良好。我们得出结论，肌病是 PD-1 抑制剂的一种罕见但独特的并发症，常累及眼外肌或球部肌肉，类似于重症肌无力。对于出现眼-球肌无力和肌酸激酶升高的接受 PD-1 抑制剂治疗的患者，肌肉活检是一项重要的检查，可区分坏死性肌病与重症肌无力患者。由于其严重的预后，坏死性肌病患者可能需要更积极的免疫治疗。
