肿瘤免疫检查点抑制剂治疗不良反应及其治疗——皮肤

doi:10.3760/cma.j.issn.1004-4221.2018.03.021

摘要
图/表
参考文献()
相关文章 (2)
点击分布统计
下载分布统计

全文: PDF (0 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS) 背景资料

摘要免疫检查点抑制剂(ICPIs)已成功应用于多种恶性肿瘤的治疗,但在应用的过程中也会发生免疫相关不良反应(irAEs)。皮肤不良反应为常见的irAEs,病变较轻者主要表现为斑丘疹、苔藓样皮炎、大疱性类天疱疮、白癜风、银屑病和硬皮病;病情较重甚至危及生命的皮肤不良反应包括史提芬强生症候群和中毒性表皮坏死松解症;其他包括药疹伴嗜酸性粒细胞增多和系统症状、Sweet′s 综合征、秃头症、Grover′s病和副肿瘤综合征等。本文将对ICPIs治疗相关皮肤不良反应诊治进行综述。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	聂芳芳
	付杰

关键词 ：免疫检查点抑制剂, 免疫相关不良反应, 皮肤不良反应

Abstract：Immune checkpoint inhibitors (ICPIs) have been successfully used in the treatment of multiple malignancies. However, immune-related adverse events (irAEs) may occur during treatment. Cutaneous adverse event (CAE) is acommon type of irAE. Mild CAEs include maculopapule,lichenoid reaction,bullous pemphigoid,vitiligo,psoriasis, and scleroderma. Severe and even life-threatening CAEs include Steven-Johnson syndromeand toxic epidermal necrolysis. Other CAEs include drug reactionwith eosinophiliaand systemic symptoms,Sweet′s syndrome,alopecia,Grover′s disease, and paraneoplastic syndrome. This paper reviews the treatment of cutaneous adverse events associated with ICPIs.

Key words： immune checkpoint inhibitors immune-related adverse events cutaneous adverse events

收稿日期: 2017-11-29

基金资助:上海申康医院发展中心促进市级医院临床技能与临床创新能力三年行动计划(16CR3112B)

通讯作者: 付杰,Email:fujie74@sjtu.edu.cn

引用本文:

聂芳芳,付杰. 肿瘤免疫检查点抑制剂治疗不良反应及其治疗——皮肤[J]. 中华放射肿瘤学杂志, 2018, 27(3): 331-334.

Nie Fangfang,Fu Jie. Cutaneous adverse events caused byimmune checkpoint inhibitors:classification and management[J]. Chinese Journal of Radiation Oncology, 2018, 27(3): 331-334.

链接本文:

http://journal12.magtechjournal.com/Jweb_fszlx/CN/10.3760/cma.j.issn.1004-4221.2018.03.021 或 http://journal12.magtechjournal.com/Jweb_fszlx/CN/Y2018/V27/I3/331

[1] 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.
[2] Khoja L,Atenafu EG,Ye Q,et al. Real-world efficacy,toxicity and clinical management of ipilimumab treatment in metastatic melanoma[J].Oncol Lett,2016,11(2):1581-1585.DOI:10.3892/ol.2015.4069.
[3] Rizvi NA,Mazieres J,Planchard D,et al. Activity and safety of nivolumab,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.
[4] Brahmer J,Reckamp KL,Baas P,et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer[J].N Engl J Med,2015,373(2):123-135.DOI:10.1056/NEJMoa1504627.
[5] Garon EB,Rizvi NA,Hui R,et al. Pembrolizumab for the treatment of non-small-cell lung cancer[J].N Engl J Med,2015,372(21):2018-2028.DOI:10.1056/NEJMoa1501824.
[6] 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.
[7] Motzer RJ,Escudier B,McDermott DF,et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma[J].N Engl J Med,2015,373(19):1803-1813.DOI:10.1056/NEJMoa1510665.
[8] Gao J,He Q,Subudhi S,et al. Review of immune-related adverse events in prostate cancer patients treated with ipilimumab:MD Anderson experience[J].Oncogene,2015,34(43):5411-5417.DOI:10.1038/onc.2015.5.
[9] Rosenberg JE,Hoffman-Censits J,Powles T,et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy:a single-arm,multicentre,phase 2 trial[J].Lancet,2016,387(10031):1909-1920.DOI:10.1016/s0140-6736(16)00561-4.
[10] Younes A,Santoro A,Shipp M,et al. Nivolumab for classical Hodgkin′s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin:a multicentre,multicohort,single-arm phase 2 trial[J].Lancet Oncol,2016,17(9):1283-1294.DOI:10.1016/s1470-2045(16)30167-x.
[11] 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.
[12] Weber JS,Kahler KC,Hauschild A.Management of immune-related adverse events and kinetics of response with ipilimumab[J].J Clin Oncol,2012,30(21):2691-2697.DOI:10.1200/jco.2012.41.6750.
[13] Minkis K,Garden BC,Wu S,et al. The risk of rash associated with ipilimumab in patients with cancer:a systematic review of the literature and meta-analysis[J].J Am Acad Dermatol,2013,69(3):e121-128.DOI:10.1016/j.jaad.2012.12.963.
[14] Gangadhar TC,Vonderheide RH.Mitigating the toxic effects of anticancer immunotherapy[J].Nat Rev Clin Oncol,2014,11(2):91-99.DOI:10.1038/nrclinonc.2013.245.
[15] Hwang SJ,Anforth R,Carlos G,et al. Cutaneous Adverse Events of New Anti-melanoma Therapies:Classification and Management[J].Actas Dermosifiliogr,2017,108(1):6-16.DOI:10.1016/j.ad.2016.05.019.
[16] Tetzlaff MT,Nagarajan P,Chon S,et al. Lichenoid Dermatologic Toxicity From Immune Checkpoint Blockade Therapy:A Detailed Examination of the Clinicopathologic Features[J].Am J Dermatopathol,2017,39(2):121-129.DOI:10.1097/dad.0000000000000688.
[17] Parakh S,Nguyen R,Opie JM,et al. Late presentation of generalised bullous pemphigoid-like reaction in a patient treated with pembrolizumab for metastatic melanoma[J].Australas J Dermatol,2016.DOI:10.1111/ajd.12488.
[18] Damsky W,Kole L,Tomayko MM.Development of bullous pemphigoid during nivolumab therapy[J].JAAD Case Rep,2016,2(6):442-444.DOI:10.1016/j.jdcr.2016.05.009.
[19] Naidoo J,Schindler K,Querfeld C,et al. Autoimmune bullous skin disorders with immune checkpoint inhibitors targeting PD-1 and PD-L1[J].Cancer Immunol Res,2016,4(5):383-389.DOI:10.1158/2326-6066.cir-15-0123.
[20] Yin ES,Totonchy MB,Leventhal JS.Nivolumab-associated vitiligo-like depigmentation in a patient with acute myeloid leukemia:a novel finding[J].JAAD Case Rep,2017,3(2):90-92.DOI:10.1016/j.jdcr.2016.10.008.
[21] Uenami T,Hosono Y,Ishijima M,et al. Vitiligo in a patient with lung adenocarcinoma treated with nivolumab:a case report[J].Lung Cancer,2017,109:42-44.DOI:10.1016/j.lungcan.2017.04.019.
[22] Wolchok JD,Neyns B,Linette G,et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma:a randomised,double-blind,multicentre,phase 2,dose-ranging study[J].Lancet Oncol,2010,11(2):155-164.DOI:10.1016/s1470-2045(09)70334-1.
[23] Assi H,Wilson KS.Immune toxicities and long remission duration after ipilimumab therapy for metastatic melanoma:two illustrative cases[J].Curr Oncol,2013,20(2):e165-169.DOI:10.3747/co.20.1265.
[24] Matsumura N,Ohtsuka M,Kikuchi N,et al. Exacerbation of Psoriasis During Nivolumab Therapy for Metastatic Melanoma[J].Acta Derm Venereol,2016,96(2):259-260.DOI:10.2340/00015555-2212.
[25] Kato Y,Otsuka A,Miyachi Y,et al. Exacerbation of psoriasis vulgaris during nivolumab for oral mucosal melanoma[J].J Eur Acad Dermatol Venereol,2016,30(10):e89-e91.DOI:10.1111/jdv.13336.
[26] Sahuquillo-Torralba A,Ballester-Sanchez R,Pujol-Marco C,et al. Pembrolizumab:a new Drug That Can Induce Exacerbations of Psoriasis[J].Actas Dermosifiliogr,2016,107(3):264-266.DOI:10.1016/j.ad.2015.07.012.
[27] Ohtsuka M,Miura T,Mori T,et al. Occurrence of Psoriasiform Eruption During Nivolumab Therapy for Primary Oral Mucosal Melanoma[J].JAMA Dermatol,2015,151(7):797-799.DOI:10.1001/jamadermatol.2015.0249.
[28] Bonigen J,Raynaud-Donzel C,Hureaux J,et al. Anti-PD1-induced psoriasis. A study of 21 patients[J].J Eur Acad Dermatol Venereol,2016.DOI:10.1111/jdv.14011.
[29] Barbosa NS,Wetater DA,Wieland CN,et al. Scleroderma induced by pembrolizumab:a case series[J].Mayo Clin Proc,2017,92(7):1158-1163.DOI:10.1016/j.mayocp.2017.03.016.
[30] Fecher LA,Agarwala SS,Hodi FS,et al. Ipilimumab and its toxicities:a multidisciplinaryapproach[J].Oncologist,2013,18(6):733-743.DOI:10.1634/theoncologist.2012-0483.
[31] Mavropoulos JC,Wang TS.Managing the skin toxicities from new melanoma drugs[J].Curr Treat Options Oncol,2014,15(2):281-301.DOI:10.1007/s11864-014-0284-6.
[32] Goldinger SM,Stieger P,Meier B,et al. Cytotoxic Cutaneous Adverse Drug Reactions during Anti-PD-1 Therapy[J].Clin Cancer Res,2016,22(16):4023-4029.DOI:10.1158/1078-0432.ccr-15-2872.
[33] Nayar N,Briscoe K,Fernandez Penas P.Toxic Epidermal Necrolysis-like Reaction With Severe Satellite Cell Necrosis Associated With Nivolumab in a Patient With Ipilimumab Refractory Metastatic Melanoma[J].J Immunother,2016,39(3):149-152.DOI:10.1097/cji.0000000000000112.
[34] Vivar KL,Deschaine M,Messina J,et al. Epidermal programmed cell death-ligand 1 expression in TEN associated with nivolumab therapy[J].J Cutan Pathol,2017,44(4):381-384.DOI:10.1111/cup.12876.
[35] Voskens CJ,Goldinger SM,Loquai C,et al. The price of tumor control:an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network[J/OL].PLoS One,2013,8(1):e53745.DOI:10.1371/journal.pone.0053745.
[36] Izzedine H,Gueutin V,Gharbi C,et al. Kidney injuries related to ipilimumab[J].Invest New Drugs,2014,32(4):769-773.DOI:10.1007/s10637-014-0092-7.
[37] Pintova S,Sidhu H,Friedlander PA,et al. Sweet′s syndrome in a patient with metastatic melanoma after ipilimumab therapy[J].Melanoma Res,2013,23(6):498-501.DOI:10.1097/cmr.0000000000000017.
[38] Zarbo A,Belum VR,Sibaud V,et al. Immune-related alopecia (areata and universalis-type) in cancer patients receiving immune checkpoint inhibitors[J].Br J Dermatol,2017,176(6):1649-1652.DOI:10.1111/bjd.15237.
[39] Munoz J,Guillot B,Girard C,et al. First report of ipilimumab-induced Grover disease[J].Br J Dermatol,2014,171(5):1236-1237.DOI:10.1111/bjd.13058.
[40] Uemura M,Faisal F,Haymaker C,et al. A case report of Grover′s disease from immunotherapy-a skin toxicity induced by inhibition of CTLA-4 but not PD-1[J].J Immunother Cancer,2016,4(1):55.DOI:10.1186/s40425-016-0157-6.
[41] Gambichler T,Strutzmann S,Tannapfel A,et al. Paraneoplastic acral vascular syndrome in a patient with metastatic melanoma under immune checkpoint blockade[J].BMC Cancer,2017,17(1):327.DOI:10.1186/s12885-017-3313-6.
[42] Brunet-Possenti F,Mignot S,Deschamps L,et al. Antiepidermis autoantibodies induced by anti-PD-1 therapy in metastatic melanoma[J].Melanoma Res,2016,26(5):540-543.DOI:10.1097/cmr.0000000000000287.
[43] Hwang SJ,Carlos G,Wakade D,et al. Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma:A single-institution cohort[J].J Am Acad Dermatol,2016,74(3):455-461.e451.DOI:10.1016/j.jaad.2015.10.029.
[44] 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.