新一代肿瘤免疫治疗不良反应及其防治原则

摘要/Abstract

摘要：近年来肿瘤免疫治疗因其在晚期肿瘤患者中的显著疗效而备受瞩目和推崇，但其常导致免疫相关不良反应。了解免疫检查点抑制剂Ipilimumab、Nivolumab和Pembrolizumab等药物的免疫相关不良反应的发生率、可能发生机制及其不良反应的评估标准及治疗原则，对恶性肿瘤的治疗具有重要意义。

刘中正，谢晓冬. 新一代肿瘤免疫治疗不良反应及其防治原则[J]. 国际肿瘤学杂志, 2017, 44(6): 460-.

Liu Zhongzheng, Xie Xiaodong. Adverse reactions of the new generation of tumor immunotherapy and its management strategy[J]. Journal of International Oncology, 2017, 44(6): 460-.

［1］ CouzinFrankel J. Breakthrough of the year 2013. Cancer immunotherapy［J］. Science, 2013, 342(6165): 1432-1433. DOI: 10.1126/science.342.6165.1432. ［2］张淑娟, 常建华. 肺癌的免疫治疗［J］. 国际肿瘤学杂志, 2015, 42(10): 776-779. DOI: 10.3760/cma.j.issn.1673422X.2015.10.016. ［3］ Ledford H. Melanoma drug wins US approval［J］. Nature, 2011, 471(7340): 561. DOI: 10.1038/471561a. ［4］ Poole RM. Pembrolizumab: first global approval［J］. Drugs, 2014, 74(16): 1973-1981. DOI: 10.1007/s4026501403145. ［5］ Kazandjian D, Suzman DL, Blumenthal G, et al. FDA approval summary: nivolumab for the treatment of metastatic nonsmall cell lung cancer with progression on or after platinumbased chemotherapy［J］. Oncologist, 2016, 21(5): 634-642. DOI: 10.1634/theoncologist.20150507. ［6］ Raedler LA. Opdivo (Nivolumab): second PD1 inhibitor receives FDA approval for unresectable or metastatic melanoma［J］. Am Health Drug Benefits, 2015, 8(Spec Feature): 180-183. ［7］ Markham A. Atezolizumab: first global approval［J］. Drugs, 2016, 76(12): 1227-1232. DOI: 10.1007/s4026501606188. ［8］ Markham A. Elotuzumab: first global approval［J］. Drugs, 2016, 76(3): 397-403. DOI: 10.1007/s4026501605400. ［9］ Weber J, Thompson JA, Hamid O, et al. A randomized, doubleblind, placebocontrolled, phase Ⅱ study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage Ⅲ or Ⅳ melanoma［J］. Clin Cancer Res, 2009, 15(17): 5591-5598. DOI: 10.1158/10780432.CCR091024. ［10］ Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma［J］. N Engl J Med, 2011, 364(26): 2517-2526. DOI: 10.1056/NEJMoa1104621. ［11］ Lynch TJ, Bondarenko I, Luft A, et al. Ipilimumab in combination with paclitaxel and carboplatin as firstline treatment in stage ⅢB/Ⅳ nonsmallcell lung cancer: results from a randomized, doubleblind, multicenter phase Ⅱ study［J］. J Clin Oncol, 2012, 30(17): 2046-2054. DOI: 10.1200/JCO.2011.38.4032. ［12］ Kwon ED, Drake CG, Scher HI, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castrationresistant prostate cancer that had progressed after docetaxel chemotherapy (CA184043): a multicentre, randomised, doubleblind, phase 3 trial［J］. Lancet Oncol, 2014, 15(7): 700-712. DOI: 10.1016/S14702045(14)701895. ［13］ Lebbé C, Weber JS, Maio M, et al. Survival followup and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase Ⅱ studies［J］. Ann Oncol, 2014, 25(11): 2277-2284. DOI: 10.1093/annonc/mdu441. ［14］ Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigatorchoice chemotherapy for ipilimumabrefractory melanoma (KEYNOTE002): a randomised, controlled, phase 2 trial［J］. Lancet Oncol, 2015, 16(8): 908-918. DOI: 10.1016/S14702045(15)000832. ［15］ Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PDL1positive, advanced nonsmallcell lung cancer (KEYNOTE010): a randomised controlled trial［J］. Lancet, 2016, 387(10027): 1540-1550. DOI: 10.1016/S01406736(15)012817. ［16］ Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma［J］. N Engl J Med, 2015, 372(26): 2521-2532. DOI: 10.1056/NEJMoa1503093. ［17］ Ribas A, Hamid O, Daud A, et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma［J］. JAMA, 2016, 315(15): 1600-1609. DOI: 10.1001/jama.2016.4059. ［18］ Weber JS, D′angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after antiCTLA4 treatment (CheckMate 037): a randomised, controlled, openlabel, phase 3 trial［J］. Lancet Oncol, 2015, 16(4): 375-384. DOI: 10.1016/S14702045(15)700768. ［19］ Rizvi NA, Mazières J,Planchard D, et al. Activity and safety of nivolumab, an antiPD1 immune checkpoint inhibitor, for patients with advanced, refractory squamous nonsmallcell lung cancer (CheckMate 063): a phase 2, singlearm trial［J］. Lancet Oncol, 2015, 16(3): 257-265. DOI: 10.1016/S14702045(15)700549. ［20］ Motzer RJ, Rini BI, Mcdermott DF, et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase Ⅱ trial［J］. J Clin Oncol, 2015, 33(13): 1430-1437. DOI: 10.1200/JCO.2014.59.0703. ［21］ Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamouscell nonsmallcell lung cancer［J］. N Engl J Med, 2015, 373(2): 123-135. DOI: 10.1056/NEJMoa1504627. ［22］ Lacouture ME, Wolchok JD, Yosipovitch G, et al. Ipilimumab in patients with cancer and the management of dermatologic adverse events［J］. J Am Acad Dermatol, 2014, 71(1): 161-169. DOI: 10.1016/j.jaad.2014.02.035. ［23］ Klein O, Ebert LM, Nicholaou T, et al. MelanAspecific cytotoxic T cells are associated with tumor regression and autoimmunity following treatment with antiCTLA4［J］. Clin Cancer Res, 2009, 15(7): 2507-2513. DOI: 10.1158/10780432.CCR082424. ［24］ Cheng R, Cooper A, Kench J, et al. Ipilimumabinduced toxicities and the gastroenterologist［J］. J Gastroenterol Hepatol, 2015, 30(4): 657-666. DOI: 10.1111/jgh.12888. ［25］ Ryder M, Callahan M, Postow MA, et al. Endocrinerelated adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution［J］. Endocr Relat Cancer, 2014, 21(2): 371-381. DOI: 10.1530/ERC130499. ［26］ Kim KW, Ramaiya NH, Krajewski KM, et al. Ipilimumab associated hepatitis: imaging and clinicopathologicfindings［J］. Invest New Drugs, 2013, 31(4): 1071-1077. DOI: 10.1007/s1063701399396. ［27］ Marrone KA, Ying W, Naidoo J. Immunerelated adverse events from immune checkpoint inhibitors［J］. Clin Pharmacol Ther, 2016, 100(3): 242-251. DOI: 10.1002/cpt.394. ［28］ Choi JN. Dermatologic adverse events to chemotherapeutic agents, Part 2: BRAF inhibitors, MEK inhibitors, and ipilimumab［J］. Semin Cutan Med Surg, 2014, 33(1): 40-48. ［29］ Nancey S, Boschetti G, Cotte E, et al. Blockade of cytotoxic Tlymphocyte antigen4 by ipilimumab is associated with a profound longlasting depletion of Foxp3+ regulatory T cells: a mechanistic explanation for ipilimumabinduced severe enterocolitis?［J］. Inflamm Bowel Dis, 2012, 18(8): E1598-E1600. DOI: 10.1002/ibd.21927. ［30］ Tarhini A. Immunemediated adverse events associated with ipilimumab ctla4 blockade therapy: the underlying mechanisms and clinical management［J］. Scientifica(Cairo), 2013, 2013: 857519. DOI: 10.1155/2013/857519.

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新一代肿瘤免疫治疗不良反应及其防治原则

Adverse reactions of the new generation of tumor immunotherapy and its management strategy

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