PD-1抑制劑致肌炎伴重癥肌無力1例分析

郭凱 朱斌 汪豐

摘 要 PD-1抑制劑的廣泛臨床使用在改善腫瘤治療效果的同時(shí)，其日漸增多的嚴(yán)重免疫相關(guān)不良反應(yīng)也值得關(guān)注。本文對(duì)1例國產(chǎn)PD-1抑制劑（信迪利單抗）在肺癌患者治療兩周期后出現(xiàn)全身酸痛，伴胸悶、氣促的案例進(jìn)行了討論分析。該患者考慮為PD-1抑制劑治療后引起免疫相關(guān)性肌炎累及心肌、橫紋肌溶解伴重癥肌無力的重疊綜合征。予以激素沖擊聯(lián)合免疫球蛋白抗炎治療、溴吡斯的明對(duì)癥治療，期間行血漿置換治療，患者治療結(jié)果好轉(zhuǎn)。因此，及時(shí)、足量的糖皮質(zhì)激素，聯(lián)合免疫球蛋白以及溴吡斯的明可以用于PD-1抑制劑引起的免疫相關(guān)性多發(fā)肌炎伴重癥肌無力的治療。

關(guān)鍵詞 PD-1抑制劑 肌炎/心肌炎 重癥肌無力 信迪利單抗 不良反應(yīng)

中圖分類號(hào)：R979.19； R969.3 文獻(xiàn)標(biāo)志碼：C 文章編號(hào)：1006-1533（2020）03-0056-04

A case report of myositis and myasthenia gravis induced by PD-1 inhibitors treatment

GUO Kai*， ZHU Bin， WANG Feng**

（Department of Pharmacy， Shanghai Cancer Center， Fudan University； Department of Oncology， Shanghai Medical College， Fudan University， Shanghai 200032， China）

ABSTRACT The clinical widespread use of PD-1 inhibitors not only improves the therapeutic effect of tumors， but also its increasing number of serious immune-related adverse reactions is also worthy of attention. Some severe， potentially lifethreatening adverse reactions such as systemic soreness with chest tightness， shortness of breath and discomfort and ECG changes， rise of creatine kinase and myocardial markers occurred in a non-small cell lung cancer treated with home-made sintilimab for two treatment courses were analyzed. This patient was considered to be immune-related myositis involving myocardium and rhabdomyolysis with myasthenia gravis （MG） overlap syndrome caused by PD-1 inhibitor treatment and was treated with steroid， immunoglobulin and symptomatic treatment of pyridostigmine and meanwhile plasma exchange was performed. The patients condition was improved after treatment. Therefore， the occurrence of severe immune-related adverse reactions should be alerted when PD-1 inhibitors need to be used. Timely and sufficient glucocorticoids combined with immunoglobulins and pyridostigmine should be used for the treatment of immune-related polymyositis with myasthenia gravis caused by PD-1 inhibitor therapy.

KEY WORDS PD-1 inhibitors； myositis/myocarditis； myasthenia gravis； sintilimab； adverse events

近年來，免疫檢查點(diǎn)抑制劑（immune checkpoint inhibitors， ICIs）的臨床應(yīng)用顯示出了巨大的優(yōu)勢(shì)和發(fā)展?jié)摿Γ瑢?duì)于腫瘤免疫治療具有重大意義。程序性死亡受體-1（programmed cell death protein-1， PD-1）是重要的免疫檢查點(diǎn)之一[1]。PD-1抑制劑能夠特異性結(jié)合T細(xì)胞表面的PD-1分子，從而阻斷導(dǎo)致腫瘤免疫耐受的PD-1/程序性死亡受體配體-1（programmed death ligand-1， PDL1）通路、重新激活免疫細(xì)胞的抗腫瘤活性，達(dá)到治療腫瘤的目的。目前，國內(nèi)上市的PD-1抑制劑有納武利尤單抗（歐狄沃）、帕博利珠單抗（可瑞達(dá)），以及國產(chǎn)特瑞普利單抗（拓益）、信迪利單抗（達(dá)伯舒）和卡瑞利珠單抗（艾立妥）。

ICIs在改善腫瘤治療效果的同時(shí)也產(chǎn)生了許多免疫相關(guān)不良反應(yīng)（immune-related adverse events， irAEs）[2]。一些威脅生命的免疫相關(guān)不良事件，包括心肌炎、心力衰竭，橫紋肌溶解、繼發(fā)呼吸困難肌炎以及致死性重癥肌無力（myasthenia gravis， MG）的病例在PD-1抑制劑治療中有報(bào)道[3-6]。……