纳武单抗联合放疗治疗非小细胞肺癌引起严重皮肤反应1例报道

赵芝梅; 刘世超; 徐夏娟; 张忠法; 聂克克; 季有信

doi:10.24920/31805

Your Location：

Home >

Browse articles >

纳武单抗联合放疗治疗非小细胞肺癌引起严重皮肤反应1例报道

Chinese Medical Sciences Journal 2018年33卷第3期页码：183-187

病例报告 | Updated：2024-04-10

- 纳武单抗联合放疗治疗非小细胞肺癌引起严重皮肤反应1例报道
- Affiliations：
  
  1 Department of Oncology, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao, Shandong 266042, China
  2 Department of Oncology, Qingdao Cancer Hospital, Qingdao, Shandong 266042, China
- Author bio：
  
  * Tel: 86-532-68665078, E-mail: mdji001@gmail.com
- Funds：
- DOI：10.24920/31805
  中图分类号：
- 网络出版日期：2018-09-20，
  
  纸质出版日期：2018-09-20
- Accepted：
Scan QR Code
赵芝梅, 刘世超, 徐夏娟, 等. 纳武单抗联合放疗治疗非小细胞肺癌引起严重皮肤反应1例报道[J]. Chinese Medical Sciences Journal, 2018,33(3):183-187.

Zhao Zhimei, Liu Shichao, Xu Xiajuan, et al. Treatment of Skin Reaction Induced by Nivolumab Combined with Radiotherapy in Non-small Cell Lung Cancer: A Case Report[J]. Chinese medical sciences journal, 2018, 33(3): 183-187.
赵芝梅, 刘世超, 徐夏娟, 等. 纳武单抗联合放疗治疗非小细胞肺癌引起严重皮肤反应1例报道[J]. Chinese Medical Sciences Journal, 2018,33(3):183-187. DOI： 10.24920/31805.

Zhao Zhimei, Liu Shichao, Xu Xiajuan, et al. Treatment of Skin Reaction Induced by Nivolumab Combined with Radiotherapy in Non-small Cell Lung Cancer: A Case Report[J]. Chinese medical sciences journal, 2018, 33(3): 183-187. DOI： 10.24920/31805.

摘要

P免疫治疗引起的皮肤反应或皮肤毒性很常见

通常表现为皮疹或红斑

可以通过润肤露或类固醇治愈。纳武单抗是一种人IgG4程序性细胞死亡蛋白1（PD-1）抑制剂

可阻断抑制T细胞激活的细胞通路

促进免疫系统清除癌细胞

FDA批准用于鳞状细胞肺癌的二线治疗

其皮肤反应发生率不到10％

多表现为感觉神经病变

皮肤脱皮

多形性红斑

白癜风和牛皮癣。放射治疗可以通过增加炎症反应和调节免疫加剧皮肤反应。许多研究发现

抗PD-1治疗联合放射治疗是一种新的有希望的肿瘤治疗方法

但发生副作用的风险可能很高。我们报道了1例晚期鳞状细胞肺癌患者

接受纳武单抗和放射治疗时发生严重的皮肤免疫相关不良事件。抗PD-1治疗可以引起皮肤过度免疫反应

放疗加重皮肤反应

二者联合可能是导致这种严重皮肤不良事件的原因。联合应用抗PD-1治疗和放射治疗时要严密防范此不良反应发生的风险。

Abstract

Skin reaction or dermatological toxicities induced by immunotherapy is common. It usually manifests skin rash or erythema and can be cured by skin lotion or steroid. Nivolumab

a human IgG4 programmed cell death protein 1 (PD-1) inhibitor

blocks T cells activation preventing signal and allows the immune system to clear cancer cells. Nivolumab was approved in the second-line therapy in squamous cell lung cancer by FDA

with less than 10% unusual skin reaction

like sensory neuropathy

peeling skin

erythema multiforme

vitiligo

and psoriasis. Radiotherapy could aggravate this skin reaction through inflammatory response and promotion of immunity. The combined treatment of anti-PD-1 and radiotherapy represented a new promising therapeutic approach in many studies

but the risk of side effects may be high. We reported a patient with advanced squamous cell lung cancer who suffered from serious skin immune-related adverse events when he was treated with nivolumab and radiotherapy. The immune overreaction of the treatment of anti-PD-1 treatment and radiotherapy might cause these serious skin adverse events. Our report warranted careful workup to reduce the risk of side effects by combinative therapy with anti-PD-1 and radiotherapy.

关键词

Keywords

references

Pardoll DM . The blockade of immune checkpoints in cancer immunotherapy . Nat Rev Cancer 2012 ; 12 ( 4 ): 252 - 64 . doi: 10.1038/nrc3239 10.1038/nrc3239 . DOI: 10.1038/nrc3239 http://doi.org/10.1038/nrc3239 http://www.nature.com/articles/nrc3239 http://www.nature.com/articles/nrc3239

Brahmer J , Reckamp KL , Baas P , et al . Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer . N Engl J Med 2015 ; 373 ( 2 ): 123 - 35 . doi: 10.1056/NEJMoa1504627 10.1056/NEJMoa1504627 . DOI: 10.1056/NEJMoa1504627 http://doi.org/10.1056/NEJMoa1504627 http://www.nejm.org/doi/10.1056/NEJMoa1504627 http://www.nejm.org/doi/10.1056/NEJMoa1504627

Belum VR , Benhuri B , Postow MA , et al . Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor . Eur J Cancer 2016 ; 60 : 12 - 25 . doi: 10.1016/j.ejca.2016.02.010 10.1016/j.ejca.2016.02.010 . DOI: 10.1016/j.ejca.2016.02.010 http://doi.org/10.1016/j.ejca.2016.02.010 https://linkinghub.elsevier.com/retrieve/pii/S0959804916001258 https://linkinghub.elsevier.com/retrieve/pii/S0959804916001258

Borghaei H , Paz-Ares L , Horn L , et al . Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer . N Engl J Med 2015 ; 373 ( 17 ): 1627 - 39 . doi: 10.1056/NEJMoa1507643 10.1056/NEJMoa1507643 . DOI: 10.1056/NEJMoa1507643 http://doi.org/10.1056/NEJMoa1507643 http://www.nejm.org/doi/10.1056/NEJMoa1507643 http://www.nejm.org/doi/10.1056/NEJMoa1507643

Rizvi NA , Mazières 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 . Lancet Oncol 2015 ; 16 ( 3 ): 257 - 65 . doi: 10.1016/S1470-2045(15)70054-9 10.1016/S1470-2045(15)70054-9 . DOI: 10.1016/S1470-2045(15)70054-9 http://doi.org/10.1016/S1470-2045(15)70054-9 https://linkinghub.elsevier.com/retrieve/pii/S1470204515700549 https://linkinghub.elsevier.com/retrieve/pii/S1470204515700549

Gettinger S , Rizvi NA , Chow LQ , et al . Nivolumab monotherapy for first-line treatment of advanced non-small-cell lung cancer . J Clin Oncol 2016 ; 34 ( 25 ): 2980 - 7 . doi: 10.1200/JCO.2016.66.9929 10.1200/JCO.2016.66.9929 . DOI: 10.1200/JCO.2016.66.9929 http://doi.org/10.1200/JCO.2016.66.9929 http://ascopubs.org/doi/10.1200/JCO.2016.66.9929 http://ascopubs.org/doi/10.1200/JCO.2016.66.9929

Haanen JBAG , Carbonnel F , Robert C , et al . Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up . Ann Oncol 2017 ; 28 ( suppl_4 ): iv119 - iv42 . doi: 10.1093/annonc/mdx225 10.1093/annonc/mdx225 . DOI: 10.1093/annonc/mdx225 http://doi.org/10.1093/annonc/mdx225 https://academic.oup.com/annonc/article/28/suppl_4/iv119/3958159 https://academic.oup.com/annonc/article/28/suppl_4/iv119/3958159

Spain L , Diem S , Larkin J . Management of toxicities of immune checkpoint inhibitors . Cancer Treat Rev 2016 ; 44 : 51 - 60 . doi: 10.1016/j.ctrv.2016.02.001 10.1016/j.ctrv.2016.02.001 . DOI: 10.1016/j.ctrv.2016.02.001 http://doi.org/10.1016/j.ctrv.2016.02.001 https://linkinghub.elsevier.com/retrieve/pii/S0305737216000165 https://linkinghub.elsevier.com/retrieve/pii/S0305737216000165

Delaney G , Jacob S , Featherstone C , et al . The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines . Cancer 2005 ; 104 ( 6 ): 1129 - 37 . doi: 10.1002/cncr.21324 10.1002/cncr.21324 . DOI: 10.1002/(ISSN)1097-0142 http://doi.org/10.1002/(ISSN)1097-0142 http://doi.wiley.com/10.1002/%28ISSN%291097-0142 http://doi.wiley.com/10.1002/%28ISSN%291097-0142

Barnett GC , West CM , Dunning AM , et al . Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype . Nat Rev Cancer 2009 ; 9 ( 2 ): 134 - 42 . doi: 10.1038/nrc2587 10.1038/nrc2587 . DOI: 10.1038/nrc2587 http://doi.org/10.1038/nrc2587 http://www.nature.com/articles/nrc2587 http://www.nature.com/articles/nrc2587

McQuestion M . Evidence-based skin care management in radiation therapy: clinical update . Semin Oncol Nurs 2011 ; 27 ( 2 ): e1 - 17 . doi: 10.1016/j.soncn.2011.02.009 10.1016/j.soncn.2011.02.009 . DOI: 10.1016/j.soncn.2011.02.009 http://doi.org/10.1016/j.soncn.2011.02.009 http://www.ncbi.nlm.nih.gov/pubmed/21514477 http://www.ncbi.nlm.nih.gov/pubmed/21514477

Ryan JL . Ionizing radiation: the good, the bad, and the ugly . J Invest Dermatol 2012 ; 132 ( 3 Pt 2 ): 985 - 93 . doi: 10.1038/jid.2011.411 10.1038/jid.2011.411 . DOI: 10.1038/jid.2011.411 http://doi.org/10.1038/jid.2011.411 http://linkinghub.elsevier.com/retrieve/pii/S0022202X15356608 http://linkinghub.elsevier.com/retrieve/pii/S0022202X15356608

Topalian SL , Hodi FS , Brahmer JR , et al . Safety, activity, and immune correlates of anti-PD-1 antibody in cancer . N Engl J Med 2012 ; 366 ( 26 ): 2443 - 54 . doi: 10.1056/NEJMoa1200690 10.1056/NEJMoa1200690 . DOI: 10.1056/NEJMoa1200690 http://doi.org/10.1056/NEJMoa1200690 http://www.nejm.org/doi/10.1056/NEJMoa1200690 http://www.nejm.org/doi/10.1056/NEJMoa1200690

Hodi FS , O'Day SJ , McDermott DF , et al . Improved survival with ipilimumab in patients with metastatic melanoma . N Engl J Med 2010 ; 363 ( 8 ): 711 - 23 . doi: 10.1056/NEJMoa1003466 10.1056/NEJMoa1003466 . DOI: 10.1056/NEJMoa1003466 http://doi.org/10.1056/NEJMoa1003466 http://www.nejm.org/doi/abs/10.1056/NEJMoa1003466 http://www.nejm.org/doi/abs/10.1056/NEJMoa1003466

Robert C , Thomas L , Bondarenko I , et al . Ipilimumab plus dacarbazine for previously untreated metastatic melanoma . N Engl J Med 2011 ; 364 ( 26 ): 2517 - 26 . doi: 10.1056/NEJMoa1104621 10.1056/NEJMoa1104621 . DOI: 10.1056/NEJMoa1104621 http://doi.org/10.1056/NEJMoa1104621 http://www.nejm.org/doi/abs/10.1056/NEJMoa1104621 http://www.nejm.org/doi/abs/10.1056/NEJMoa1104621

Weber JS , Yang JC , Atkins MB , et al . Toxicities of immunotherapy for the practitioner . J Clin Oncol 2015 ; 33 ( 18 ): 2092 - 9 . doi: 10.1200/JCO.2014.60.0379 10.1200/JCO.2014.60.0379 . DOI: 10.1200/JCO.2014.60.0379 http://doi.org/10.1200/JCO.2014.60.0379 http://ascopubs.org/doi/10.1200/JCO.2014.60.0379 http://ascopubs.org/doi/10.1200/JCO.2014.60.0379

Hasan Ali O , Diem S , Markert E , et al . Characterization of nivolumab-associated skin reactions in patients with metastatic non-small cell lung cancer . Oncoimmunology 2016 ; 5 ( 11 ): e1231292 . doi: 10.1080/2162402X.2016.1231292 10.1080/2162402X.2016.1231292 . DOI: 10.1080/2162402X.2016.1231292 http://doi.org/10.1080/2162402X.2016.1231292 https://www.tandfonline.com/doi/full/10.1080/2162402X.2016.1231292 https://www.tandfonline.com/doi/full/10.1080/2162402X.2016.1231292

Hinrichs CS , Restifo NP . Reassessing target antigens for adoptive T-cell therapy . Nat Biotechnol 2013 ; 31 ( 11 ): 999 - 1008 . doi: 10.1038/nbt.2725 10.1038/nbt.2725 . DOI: 10.1038/nbt.2725 http://doi.org/10.1038/nbt.2725 http://www.nature.com/articles/nbt.2725 http://www.nature.com/articles/nbt.2725

Singh M , Alavi A , Wong R , et al . Radiodermatitis: a review of our current understanding . Am J Clin Dermatol 2016 ; 17 ( 3 ): 277 - 92 . doi: 10.1007/s40257-016-0186-4 10.1007/s40257-016-0186-4 . DOI: 10.1007/s40257-016-0186-4 http://doi.org/10.1007/s40257-016-0186-4 http://link.springer.com/10.1007/s40257-016-0186-4 http://link.springer.com/10.1007/s40257-016-0186-4

Kim JH , Kolozsvary AJ , Jenrow KA , et al . Mechanisms of radiation-induced skin injury and implications for future clinical trials . Int J Radiat Biol 2013 ; 89 ( 5 ): 311 - 8 . doi: 10.3109/09553002.2013.765055 10.3109/09553002.2013.765055 . DOI: 10.3109/09553002.2013.765055 http://doi.org/10.3109/09553002.2013.765055 http://www.tandfonline.com/doi/full/10.3109/09553002.2013.765055 http://www.tandfonline.com/doi/full/10.3109/09553002.2013.765055

Amber KT , MI Shiman , EV Badiavas . The use of antioxidants in radiotherapy-induced skin toxicity . Integr Cancer Ther 2014 ; 13 ( 1 ): 38 - 45 . doi: 10.1177/1534735413490235 10.1177/1534735413490235 . DOI: 10.1177/1534735413490235 http://doi.org/10.1177/1534735413490235 http://journals.sagepub.com/doi/10.1177/1534735413490235 http://journals.sagepub.com/doi/10.1177/1534735413490235

Holler V , Buard V , Gaugler MH , et al . Pravastatin limits radiation-induced vascular dysfunction in the skin . J Invest Dermatol 2009 ; 129 ( 5 ): 1280 - 91 . doi: 10.1038/jid.2008.360 10.1038/jid.2008.360 . DOI: 10.1038/jid.2008.360 http://doi.org/10.1038/jid.2008.360 http://linkinghub.elsevier.com/retrieve/pii/S0022202X15343244 http://linkinghub.elsevier.com/retrieve/pii/S0022202X15343244

Xie G , Gu D , Zhang L , et al . A rapid and systemic complete response to stereotactic body radiation therapy and pembrolizumab in a patient with metastatic renal cell carcinoma . Cancer Biol Ther 2017 ; 18 ( 8 ): 547 - 51 . doi: 10.1080/15384047.2017.1345389 10.1080/15384047.2017.1345389 . DOI: 10.1080/15384047.2017.1345389 http://doi.org/10.1080/15384047.2017.1345389 https://www.tandfonline.com/doi/full/10.1080/15384047.2017.1345389 https://www.tandfonline.com/doi/full/10.1080/15384047.2017.1345389

Yuan Z , Fromm A , Ahmed KA , et al . Radiotherapy rescue of a nivolumab-refractory immune response in a patient with PD-L1-negative metastatic squamous cell carcinoma of the lung . J Thorac Oncol 2017 ; 12 ( 9 ): e135 - 6 . doi: 10.1016/j.jtho.2017.04.029 10.1016/j.jtho.2017.04.029 . DOI: 10.1016/j.jtho.2017.04.029 http://doi.org/10.1016/j.jtho.2017.04.029 https://linkinghub.elsevier.com/retrieve/pii/S1556086417303635 https://linkinghub.elsevier.com/retrieve/pii/S1556086417303635

Lu CS , Liu JH . Pneumonitis in cancer patients receiving anti-PD-1 and radiotherapies: three case reports . Medicine (Baltimore) 2017 ; 96 ( 1 ): e5747 . doi: 10.1097/MD.0000000000005747 10.1097/MD.0000000000005747 . DOI: 10.1097/MD.0000000000005747 http://doi.org/10.1097/MD.0000000000005747 http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00005792-201701060-00036 http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00005792-201701060-00036

Youinou P , Pers JO . The late news on baff in autoimmune diseases . Autoimmun Rev 2010 ; 9 ( 12 ): 804 - 6 . doi: 10.1016/j.autrev.2010.06.011 10.1016/j.autrev.2010.06.011 . DOI: 10.1016/j.autrev.2010.06.011 http://doi.org/10.1016/j.autrev.2010.06.011 http://linkinghub.elsevier.com/retrieve/pii/S156899721000145X http://linkinghub.elsevier.com/retrieve/pii/S156899721000145X

Sutherland AP , Ng LG , Fletcher CA , et al . BAFF augments certain Th1-associated inflammatory responses . J Immunol 2005 ; 174 ( 9 ): 5537 - 44 . DOI: 10.4049/jimmunol.174.9.5537 http://doi.org/10.4049/jimmunol.174.9.5537 http://www.jimmunol.org/cgi/doi/10.4049/jimmunol.174.9.5537 http://www.jimmunol.org/cgi/doi/10.4049/jimmunol.174.9.5537

Zen M , Canova M , Campana C , et al . The kaleidoscope of glucorticoid effects on immune system . Autoimmun Rev 2011 ; 10 ( 6 ): 305 - 10 . doi: 10.1016/j.autrev.2010.11.009 10.1016/j.autrev.2010.11.009 . DOI: 10.1016/j.autrev.2010.11.009 http://doi.org/10.1016/j.autrev.2010.11.009 http://linkinghub.elsevier.com/retrieve/pii/S1568997211000048 http://linkinghub.elsevier.com/retrieve/pii/S1568997211000048

Cain DW , Cidlowski JA . Immune regulation by glucocorticoids . Nat Rev Immunol 2017 ; 17 ( 4 ): 233 - 47 . doi: 10.1038/nri.2017.1 10.1038/nri.2017.1 . DOI: 10.1038/nri.2017.1 http://doi.org/10.1038/nri.2017.1 http://www.nature.com/articles/nri.2017.1 http://www.nature.com/articles/nri.2017.1

de Golian E , Kwong BY , Swetter SM . Cutaneous complications of targeted melanoma therapy . Curr Treat Options Oncol 2016 ; 17 : 57 . doi: 10.1007/s11864-016-0434-0 10.1007/s11864-016-0434-0 . DOI: 10.1007/s11864-016-0434-0 http://doi.org/10.1007/s11864-016-0434-0 http://link.springer.com/10.1007/s11864-016-0434-0 http://link.springer.com/10.1007/s11864-016-0434-0

Nayar N , Briscoe K , Fernandez PP . Toxic epidermal necrolysis-like reaction with severe satellite cell necrosis associated with nivolumab in a patient with ipilimumab refractory metastatic melanoma . J Immunother 2016 ; 39 ( 3 ): 149 - 52 . doi: 10.1097/CJI.0000000000000112 10.1097/CJI.0000000000000112 . DOI: 10.1097/CJI.0000000000000112 http://doi.org/10.1097/CJI.0000000000000112 https://insights.ovid.com/crossref?an=00002371-201604000-00005 https://insights.ovid.com/crossref?an=00002371-201604000-00005

浏览量

1588

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

关联资源

PD-1/PD-L1调控及其在肿瘤靶向治疗的前景展望