Severe pneumonitis after nivolumab treatment in a patient with melanoma.
Severe pneumonitis after nivolumab treatment in a patient with melanoma.
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黑色素瘤患者接受纳武利尤单抗治疗后出现严重肺炎。
DOI：
10.1016/j.alit.2016.04.009
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Matsushita T,Kasahara K.
中科院分区：
文献类型：
--
作者：
1.5.Watanabe S;Kimura H;Takato H;Waseda Y;Hara J;Sone T;Abo M;Maeda S;Matsushita T,Kasahara K.
Nivolumab是一种免疫检查点抑制剂，可结合程序性死亡1（PD-1）受体并阻断其与PD-L1和PD-L2的相互作用，从而逆转肿瘤诱导的肿瘤特异性T细胞抑制。Nivolumab目前被批准用于治疗转移性黑色素瘤、鳞状细胞肺癌和肾细胞癌。虽然通常耐受良好，但纳武单抗可诱导免疫相关性肺炎。我们在此描述了nivolumab治疗黑色素瘤后严重肺炎的病例。一位73岁的女性转移性黑色素瘤（脑，肺）提出了我们的机构与发热，疲劳，干咳。在就诊前五个月，她开始接受纳武利尤单抗（2 mg/kg，每三周一次）治疗。经过六个周期的治疗后，在就诊前一周，她出现发热、疲劳和干咳。她的既往病史对于覆膜支架术后胸主动脉瘤状态具有重要意义。她不吸烟，没有慢性肺病史。检查时，体温为37.0 ℃，血压为121/75 mm Hg，心率为82/min，室内空气氧饱和度为95%。她的体检结果并不明显。实验室检查显示白色血细胞计数为10，970/μL，中性粒细胞占85.6%，淋巴细胞占6.1%，C反应蛋白水平为14.3 mg/dL（正常< 0.3 mg/dL），血清乳酸脱氢酶（LDH）水平为138 IU/L（正常，119 e229 IU/L），Krebs von den Lungen-6（KL-6）水平为250 U/mL（正常< 500 U/mL）。室内空气动脉血气分析显示pH值为7.479，PaCO 2为37.6 mmHg，PaO 2为61.0 mmHg。胸部X线片显示右肺浸润和右肋膈角变钝。胸部计算机断层扫描（CT）显示实变伴支气管充气征、磨玻璃样衰减和斑片状阴影，主要位于右肺。这些异常主要涉及依赖肺区域。还存在右侧胸腔积液。在左下叶发现转移性肺肿瘤，但肿瘤周围未见异常（图1）。虽然痰培养没有发现任何微生物，包括分枝杆菌和真菌，但由于她的症状和CT结果，她最初被诊断为细菌性肺炎。停用纳武利尤单抗，并开始使用他唑巴坦/哌拉西林（TAZ/PIPC）和左氧氟沙星（LVFX）抗生素，但其症状未改善。在住院第11天，TAZ/PIPC转换为美罗培南（MEPM）。然而，她出现进行性呼吸困难伴严重低氧血症，CT成像显示弥漫性实变、磨玻璃样变和胸腔积液加重，提示弥漫性肺泡损伤。在住院第16天，她被转移到重症监护室，并开始接受机械通气。血清表面活性蛋白-D水平升高至213.7 ng/mL（正常值< 110 ng/mL），但LDH（243 IU/L）和KL-6（327 U/mL）在正常范围内。支气管肺泡灌洗（BAL）显示总细胞计数为3.1 × 105个细胞/mL，其中巨噬细胞占77.7%，淋巴细胞占8.7%，中性粒细胞占14.3%，没有细菌、真菌或恶性肿瘤的证据。胸腔积液也是无菌的。超声心动图未显示任何潜在心功能不全。她的PaO 2/FIO 2比值为131，她最终被诊断为继发于纳武利尤单抗治疗的急性呼吸窘迫综合征（4级）。开始静脉甲泼尼龙（mPSL）脉冲治疗（1 g/天，持续3天）和西维来司他钠水合物连续输注。她的呼吸...
Nivolumab is an immune checkpoint inhibitor that binds to the Programmed death 1 (PD-1) receptor and blocks its interaction with PD-L1 and PD-L2, thereby reversing tumor-induced suppression of tumor-specific T cells. 1, 2 Nivolumab is currently approved for the treatment of metastatic melanoma, squamous cell lung cancer, and renal cell cancer. Although generally well tolerated, nivolumab can induce immune-related pneumonitis. We herein describe a case of severe pneumonitis after nivolumab treatment for melanoma. A 73-year-old woman with metastatic melanoma (brain, lung) presented to our institution with fever, fatigue, and non-productive cough. Five months prior to presentation, she had begun treatment with nivolumab (2 mg/kg, every three weeks). After six cycles of treatment, one week prior to presentation, she developed fever, fatigue, and non-productive cough. Her past medical history was significant for thoracic aortic aneurysm status post stent graft. She was a nonsmoker and had no history of chronic lung disease. On examination, body temperature was 37.0 C, blood pressure was 121/75 mm Hg, heart rate was 82/min, and oxygen saturation on room air was 95%. Her physical examination was unremarkable. Laboratory tests demonstrated white blood cell count of 10,970/μL with 85.6% neutrophils and 6.1% lymphocytes, C-reactive protein level of 14.3 mg/dL (normal< 0.3 mg/dL), serum lactate dehydrogenase (LDH) level of 138 IU/L (normal, 119e229 IU/L), and Krebs von den Lungen-6 (KL-6) level of 250 U/mL (normal< 500 U/mL). Arterial blood gas analysis on room air showed pH of 7.479, PaCO2 of 37.6 mmHg and PaO2 of 61.0 mmHg. Chest radiography showed a right lung infiltrate and blunting of the right costophrenic angle. Chest computed tomography (CT) scan revealed a consolidation with air bronchograms, ground-glass attenuations, and patchy shadows, predominantly in the right lung. These abnormalities mainly involved the dependent lung regions. A right pleural effusion was also present. A metastatic lung tumor was found in the left lower lobe, but no abnormalities were observed around the tumor (Fig. 1). Although sputum culture did not reveal any microorganisms, including mycobacteria and fungi, she was initially diagnosed with bacterial pneumonia due to her symptoms and CT findings. Nivolumab was discontinued, and tazobactam/piperacillin (TAZ/PIPC) and levofloxacin (LVFX) antibiotics were initiated, but her symptoms did not improve. On hospital day 11, TAZ/PIPC was switched to meropenem (MEPM). However, she developed progressive dyspnea with severe hypoxemia, and the diffuse consolidation, ground-glass attenuations, and pleural effusions worsened on CT imaging, in a pattern suggestive of diffuse alveolar damage. On hospital day 16, she was transferred to the intensive care unit and started on mechanical ventilation. The serum level of surfactant protein-D was increased to 213.7 ng/mL (normal< 110 ng/mL), but LDH (243 IU/L) and KL-6 (327 U/mL) were within normal limits. Bronchoalveolar lavage (BAL) showed a total cell count of 3.1 Â105 cells/mL with 77.7% macrophages, 8.7% lymphocytes, and 14.3% neutrophils, with no evidence of bacteria, fungi or malignancy. The pleural fluid was also sterile. An echocardiogram did not demonstrate any underlying cardiac dysfunction. Her PaO2/FIO2 ratio was 131, and she was ultimately diagnosed with acute respiratory distress syndrome secondary to nivolumab treatment (Grade 4). Intravenous methylprednisolone (mPSL) pulse therapy (1 g per day for three days) and continuous infusion of sivelestat sodium hydrate were initiated. Her respiratory …
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纳武单抗（抗 PD-1；BMS-936558；ONO-4538）治疗晚期实体瘤患者：I 期试验中的生存率和长期安全性。
DOI：
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发表时间：
2013
期刊：
影响因子：
--
作者：
S. Topalian;M. Sznol;J. Brahmer;David F. McDermott;David C. Smith;S. Gettinger;J. Taube;Charles G. Drake;Drew M. Pardoll;J. Powderly;Richard D. Carvajal;J. Sosman;Michael B Atkins;S. Antonia;D. Spigel;Donald P. Lawrence;G. Kollia;A. Gupta;J. Wigginton;F. Hodi
通讯作者：
F. Hodi
DOI：
10.1200/jco.2009.26.7609
发表时间：
2010-07-01
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Brahmer JR;Drake CG;Wollner I;Powderly JD;Picus J;Sharfman WH;Stankevich E;Pons A;Salay TM;McMiller TL;Gilson MM;Wang C;Selby M;Taube JM;Anders R;Chen L;Korman AJ;Pardoll DM;Lowy I;Topalian SL
通讯作者：
Topalian SL
黑色素瘤患者中纳武利尤单抗诱导的机化性肺炎。
影响因子：
2.4
作者：
T. Sano;H. Uhara;Y. Mikoshiba;A. Kobayashi;R. Uchiyama;K. Tateishi;Hiroshi Yamamoto;R. Okuyama
通讯作者：
R. Okuyama
影响因子：
158.5
作者：
Robert, Caroline;Long, Georgina V.;Ascierto, Paolo A.
通讯作者：
Ascierto, Paolo A.
DOI：
10.1056/nejmoa1200690
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Topalian SL;Hodi FS;Brahmer JR;Gettinger SN;Smith DC;McDermott DF;Powderly JD;Carvajal RD;Sosman JA;Atkins MB;Leming PD;Spigel DR;Antonia SJ;Horn L;Drake CG;Pardoll DM;Chen L;Sharfman WH;Anders RA;Taube JM;McMiller TL;Xu H;Korman AJ;Jure-Kunkel M;Agrawal S;McDonald D;Kollia GD;Gupta A;Wigginton JM;Sznol M
通讯作者：
Sznol M