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程序性死亡-1抑制剂帕博利珠单抗引起的免疫相关性肺炎:一例报告及文献综述

[Immune-related pneumonitis caused by programmed death-1 inhibitor Pembrolizumab: a case report and literature review].

作者信息

Chen Y L, Zhao J, Jia R, Wang H Y, Zheng J, Bai C Q, Wang M Z, Xu J M

机构信息

Department of Digestive Medical Oncology, the Affiliated Hospital of Military Medical Sciences, Beijing 100071, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2017 Oct 12;40(10):736-743. doi: 10.3760/cma.j.issn.1001-0939.2017.10.006.

Abstract

To investigate the risk factors, clinical manifestations, radiological features, diagnosis, treatment and prognosis of immune-related pneumonitis caused by programmed death-1(PD-1)/PD-L1 inhibitors. The clinical data of immune-related pneumonitis caused by PD-1 inhibitor Pembrolizumab in a patient with advanced esophageal carcinoma admitted to the 307(th) Hospital of Chinese People's Liberation Army was retrospectively analyzed and the related literatures were reviewed. We searched Medline database using the keywords"PD-1 inhibitor","PD-L1 inhibitor","Pembrolizumab","Nivolumab","Atezolizumab"combined with"Pneumonitis"by Mar 31, 2017. The patient was a 60-year-old male presented with progression disease after surgery, local radiation and couples of chemotherapy for his esophageal carcinoma. Then pembrolizumab, a kind of PD-l inhibitors, was given intravenously every 3 weeks with the average dosage 3 mg per kg. After six cycles of pembrolizumab, the patient began to have fever, cough and dyspnea, which aggravated gradually. Chest CT showed diffuse ground glass opacity, exudation and consolidation in both lungs and little pleural effusion in the right side. Cellular interstitial pneumonitis was confirmed by pathological examination. The patient's symptoms were alleviated after enough steroids and chest CT showed pulmonary infiltration was also absorbed. But the pneumonitis reoccurred twice after stopping or tapering steroids quickly and could also be controlled by using steroids again. Now the patient was still given steroids treatment and the primary esophageal cancer remained stable. 14 articles were retrieved and 88 cases of immune-related pneumonitis caused by PD-1/PD-L1 inhibitors were reported. Among these 89 cases with immune-related pneumonitis, both male and female could attack and the median age was 67 years old. Most cases were grade 1 or 2. The common clinical manifestations were dyspnea, cough, fever and other immune-related damages. And about 20% patients had no symptoms. Ground glass opacities, reticular opacities, consolidation and centrilobular nodules were the common radiological features. The commonest histologic pattern of pneumonitis associated with anti-PD-1/PD-L1 therapy on lung biopsy was organizing pneumonia. Adequate steroid and tapering slowly is the standard treatment. Immunosuppressive agents could be added in some serious cases. The prognosis was relatively good. Most patients were alleviated but few patients died of progression disease or infections during treatment. Immune-related pneumonitis associated with PD-l/PD-L1 inhibitor should be aware of; early detection, early treatment, and the prognosis could be better.

摘要

探讨程序性死亡蛋白1(PD-1)/程序性死亡配体1(PD-L1)抑制剂所致免疫相关性肺炎的危险因素、临床表现、影像学特征、诊断、治疗及预后。回顾性分析解放军第307医院收治的1例晚期食管癌患者使用PD-1抑制剂帕博利珠单抗后发生免疫相关性肺炎的临床资料,并复习相关文献。检索Medline数据库,使用关键词“PD-1抑制剂”“PD-L1抑制剂”“帕博利珠单抗”“纳武利尤单抗”“阿特珠单抗”并结合“肺炎”,检索截至2017年3月31日的文献。患者为60岁男性,食管癌术后、局部放疗及多次化疗后疾病进展。随后每3周静脉给予1种PD-1抑制剂帕博利珠单抗,平均剂量为3mg/kg。帕博利珠单抗治疗6个周期后,患者开始出现发热、咳嗽和呼吸困难,且逐渐加重。胸部CT显示双肺弥漫性磨玻璃影、渗出及实变,右侧少量胸腔积液。病理检查确诊为细胞性间质性肺炎。给予足量激素治疗后患者症状缓解,胸部CT显示肺部浸润也吸收。但在快速停用或减量激素后肺炎复发2次,再次使用激素仍可控制。目前患者仍接受激素治疗,原发性食管癌病情稳定。检索到14篇文献,共报道88例PD-1/PD-L1抑制剂所致免疫相关性肺炎。在这89例免疫相关性肺炎患者中,男女均可发病,中位年龄为67岁。多数病例为1级或2级。常见临床表现为呼吸困难、咳嗽、发热等免疫相关损害。约20%的患者无症状。磨玻璃影、网状影、实变及小叶中心结节是常见的影像学特征。肺活检中与抗PD-1/PD-L1治疗相关的肺炎最常见的组织学类型是机化性肺炎。足量激素并缓慢减量是标准治疗方法。严重病例可加用免疫抑制剂。预后相对较好。多数患者病情缓解,但少数患者在治疗期间死于疾病进展或感染。应警惕与PD-1/PD-L1抑制剂相关的免疫相关性肺炎;早期发现、早期治疗,预后可能较好。

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