免疫检查点抑制剂治疗合并乙型肝炎或丙型肝炎的晚期非小细胞肺癌的安全性及疗效分析_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

陈澄 ¹ , 何方凯 ² , 沈续瑞 ¹ , 黄建安 ¹ ,  管小俊 ¹

1. ;
2. ;

Corresponding author：

管小俊, Email: gxj309@126.com

Keywords：

非小细胞肺癌; 乙型病毒性肝炎; 丙型病毒性肝炎; 免疫检查点抑制剂

DOI：

10.7507/1671-6205.202206049

Video：

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目的探讨合并乙型肝炎或丙型肝炎的晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）治疗的安全性和疗效。方法回顾性分析5例合并乙型肝炎或丙型肝炎的NSCLC，观察谷丙转氨酶（alanine aminotransferase，ALT）水平、病毒载量和总生存期。结果 1例活动性乙型肝炎和1例活动性丙型肝炎启动ICIs治疗时，ALT升高，加用抗病毒和保肝治疗，ALT即恢复正常。2例活动性和1例慢性乙型肝炎ICIs治疗，ALT持续正常水平。2例完全缓解，3例部分缓解，目前死亡2例，最长总生存期35.7个月，其余3例仍在随访中。结论乙型肝炎或丙型肝炎不影响ICIs在NSCLC中的治疗地位，包括在部分NSCLC的一线治疗，全程监测肝功能和病毒拷贝数，推荐联合抗病毒治疗（特别对合并乙型肝炎），个体化调整抗病毒时机及疗程。

Citation： 陈澄, 何方凯, 沈续瑞, 黄建安, 管小俊. 免疫检查点抑制剂治疗合并乙型肝炎或丙型肝炎的晚期非小细胞肺癌的安全性及疗效分析. Chinese Journal of Respiratory and Critical Care Medicine, 2022, 21(8): 587-591. doi: 10.7507/1671-6205.202206049 Copy

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14.	El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet, 2017, 389(10088): 2492-2502.
15.	Kothapalli A, Khattak MA. Safety and efficacy of anti-PD-1 therapy for metastatic melanoma and non-small-cell lung cancer in patients with viral hepatitis: a case series. Melanoma Res, 2018, 28(2): 155-158.
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1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
2. Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet, 2017, 389(10066): 255-265.
3. Borghaei H, Gettinger S, Vokes EE, et al. Five-year outcomes from the randomized, phase Ⅲ trials CheckMate 017 and 057: nivolumab versus docetaxel in previously treated non-small-cell lung cancer. J Clin Oncol, 2021, 39(7): 723-733.
4. Herbst RS, Garon EB, Kim DW, et al. Five year survival update from KEYNOTE-010: pembrolizumab versus docetaxel for previously treated, programmed death-ligand 1-positive advanced NSCLC. J Thorac Oncol, 2021, 16(10): 1718-1732.
5. Polaris Observatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol, 2018, 3(6): 383-403.
6. Polaris Observatory HCV Collaborators. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol, 2017, 2(3): 161-176.
7. Cui FQ, Shen LP, Li L, et al. Prevention of chronic hepatitis B after 3 decades of escalating vaccination policy, China. Emerg Infect Dis, 2017, 23(5): 765-772.
8. Hei FX, Ye SD, Ding GW, et al. Epidemiological analysis on reported hepatitis C cases in China from 2012 to 2016. Biomed Environ Sci, 2018, 31(10): 773-776.
9. 周巧, 余荷, 梁宗安. 免疫检查点抑制剂导致免疫相关性肺炎. 中国呼吸与危重监护杂志, 2021, 20(10): 753-756.
10. 周永召, 李为民. 肺癌免疫检查点抑制剂治疗的不良反应及其防治. 中华结核和呼吸杂志, 2020, 43(2): 91-95.
11. Larrubia JR, Moreno-Cubero E, Lokhande MU, et al. Adaptive immune response during hepatitis C virus infection. World J Gastroenterol, 2014, 20(13): 3418-3430.
12. Balmasova IP, Yushchuk ND, Mynbaev OA, et al. Immunopathogenesis of chronic hepatitis B. World J Gastroenterol, 2014, 20(39): 14156-14171.
13. Zhu AX, Finn RS, Edeline J, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol, 2018, 19(7): 940-952.
14. El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet, 2017, 389(10088): 2492-2502.
15. Kothapalli A, Khattak MA. Safety and efficacy of anti-PD-1 therapy for metastatic melanoma and non-small-cell lung cancer in patients with viral hepatitis: a case series. Melanoma Res, 2018, 28(2): 155-158.
16. Pertejo-Fernandez A, Ricciuti B, Hammond SP, et al. Safety and efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer and hepatitis B or hepatitis C infection. Lung Cancer, 2020, 145: 181-185.
17. Zhang XY, Tian D, Chen Y, et al. Association of hepatitis B virus infection status with outcomes of non-small cell lung cancer patients undergoing anti-PD-1/PD-L1 therapy. Transl Lung Cancer Res, 2021, 10(7): 3191-3202.
18. He MK, Peng C, Zhao Y, et al. Comparison of HBV reactivation between patients with high HBV-DNA and low HBV-DNA loads undergoing PD-1 inhibitor and concurrent antiviral prophylaxis. Cancer Immunol Immunother, 2021, 70(11): 3207-3216.
19. Wuyts L, Janssens A, Vonghia L, et al. Nivolumab and anti-HCV activity, a case report. Acta Clin Belg, 2021, 76(5): 392-396.
20. Fukuda R, Sugawara S, Kondo Y. Immune checkpoint inhibitor can reduce HCV-RNA without liver damage. Intern Med, 2020, 59(18): 2245-2248.

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免疫检查点抑制剂治疗合并乙型肝炎或丙型肝炎的晚期非小细胞肺癌的安全性及疗效分析

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