癌症免疫治療的不良反應與處置

The Management of Immune Related Adverse Events Associated with Cancer Immunotherapy

10.3966/168395442018061801003

陳玉紛(Yu-Fen Chen)；葉人華(Ren-Hua Ye)；張慕民(Mu-Ming Chang)；吳宜穎(Yi-Ying Wu)

癌症免疫治療 ； 免疫相關不良反應 ； cancer immunotherapy ； immune related adverse events (irAEs)

腫瘤護理雜誌

18卷1期（2018 / 06 / 01）

29 - 38

繁體中文

1982年起惡性腫瘤高居台灣十大死因首位，每年會奪走4萬多人的性命，且癌症發生率節節高升，面對高死亡率及高發生率的癌症，近年來，其相關的治療也日新月異，從化學治療、標靶治療，自2010年後更進一步發展到免疫治療，除所費不貲外，相關的副作用也和傳統治療大不相同，免疫治療的副作用統稱為免疫相關不良反應（immune-related adverse events, irAEs），可能影響全身的器官或組織，甚至有致命的威脅。因此，醫護人員應密切監測及追蹤病人的免疫相關不良反應，藉以早期鑑別不良反應的程度分級，並依據處置重點進行治療，期望能使癌症免疫治療達到最大療效。

In Taiwan, malignant neoplasms have ranked top ten causes of death since 1982, claiming the lives of more than 40,000 people each year. As the incidence of cancer rises steadily carrying high mortality in recent years, relevant treatments are also seen changing almost from day to day and from chemotherapy to target therapy, then evolving further to cancer immunotherapy in 2010. Apart from the fact that immunotherapy is very costly, the related side effects, far from those of the traditional treatments, are also an eyebrow raiser. The side effects of immunotherapy are collectively referred to as Immune-related adverse events (irAEs), which may affect organs or tissues throughout the body, or even present a fatal threat. Therefore, health care professionals should closely monitor and follow up on patients' immune-related adverse events in order to early identify the adverse events and to evaluate the level of response so further treatment can be planned according to achieve the maximum expected effect from the cancer immunotherapy.

1. Barroso-Sousa, R.,Barry, W. T.,Garrido-Castro, A. C.,Hodi, F. S.,Min, L.,Krop, I. E.,Tolaney, S. M.(2018).Incidence of endocrine dysfunc tion following the use of different immune checkpoint inhibitor regimens: A systematic review and meta-analysis.JAMA Oncology,4(2),173-182.
2. Bernardo, S. G.,Moskalenko, M.,Pan, M.,Shah, S.,Sidhu, H. K.,Sicular, S.,Saenger, Y. M.(2013).Elevated rates of transaminitis during ipilimumab therapy for metastatic melanoma.Melanoma Research,23(1),47-54.
3. Brahmer, J. R.,Lacchetti, C.,Schneider, B. J.,Atkins, M. B.,Brassil, K. J.,Caterino, J. M.,Thompson, J. A.(2018).Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline.Journal of Clinical Oncology
4. Couzin-Frankel, J.(2013).Breakthrough of the year 2013.Science,342(6165),1432-1433.
5. European Society for Medical Oncology (ESMO) (2017). Patient guide on immunotherapy-related side effects and their management. Retrieved from http://www.esmo.org/content/download/124130/2352601/file/ESMO-Patient-Guide-on-Immunotherapy-Side-Effects.pdf
6. Fay, A. P.,Moreira, R. B.,Nunes Filho, P. R. S.,Albuquerque, C.,Barrios, C. H.(2016).The management of immune-related adverse events associated with immune checkpoint blockade.Expert Review of Quality of Life in Cancer Care,1,89-97.
7. Haanen, J.,Carbonnel, F.,Robert, C.,Kerr, K. M.,Peters, S.,Larkin, J.,Committee, E. G.(2017).Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.Annals of Oncology,28(suppl_4),iv119-iv142.
8. Hamid, O.,Robert, C.,Daud, A.,Hodi, F. S.,Hwu, W. J.,Kefford, R.,Ribas, A.(2013).Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma.New England Journal of Medicine,369(2),134-144.
9. Hammers, H. J.,Plimack, E. R.,Infante, J. R.,Rini, B. I.,McDermott, D. F.,Lewis, L. D.,Amin, A.(2017).Safety and efficacy of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma.Journal of Clinical Oncology,35(34),3851-3858.
10. Hodi, F. S.,O’Day, S. J,McDermott, D. F.,Weber, R. W.,Sosman, J. A.,Haanen, J. B.,Urba, W. J.(2010).Improved survival with ipilimumab in patients with metastatic melanoma.New England Journal of Medicine,363(8),711-723.
11. Lacouture, M. E.,Wolchok, J. D.,Yosipovitch, G.,Kahler, K. C.,Busam, K. J.,Hauschild, A.(2014).Ipilimumab in patients with cancer and the management of dermatologic adverse events.Journal of the American Academy of Dermatology,71(1),161-169.
12. Minkis, K.,Garden, B. C.,Wu, S.,Pulitzer, M. P.,Lacouture, M. E.(2013).The risk of rash associated with ipilimumab in patients with cancer: A systematic review of the literature and meta-analysis.Journal of the American Academy of Dermatology,69(3),e121-e128.
13. Molhoj, M.,Crommer, S.,Brischwein, K.,Rau, D.,Sriskandarajah, M.,Hoffmann, P.,Baeuerle, P. A(2007).CD19-/CD3-bispecific antibody of the BiTE class is far superior to tandem dia-body with respect to redirected tumor cell lysis.Molecular Immunology,44(8),1935-1943.
14. Momtaz, P.,Park, V.,Panageas, K. S.,Postow, M. A.,Callahan, M.,Wolchok, J. D.,Chapman, P. B.(2015).Safety of infusing ipilimumab over 30 minutes.Journal of Clinical Oncology,33(30),3454-3458.
15. Naidoo, J.,Page, D. B.,Li, B. T.,Connell, L. C.,Schindler, K.,Lacouture, M. E.,Wolchok, J. D.(2015).Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies.Annals of Oncology,26(12),2375-2391.
16. Naidoo, J.,Wang, X.,Woo, K. M.,Iyriboz, T.,Halpenny, D.,Cunningham, J.,Hellmann, M. D.(2017).Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy.Journal of Clinical Oncology,35(7),709-717.
17. Nishino, M.,Giobbie-Hurder, A.,Hatabu, H.,Ramaiya, N. H.,Hodi, F. S.(2016).Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer: A systematic review and meta-analysis.JAMA Oncology,2(12),1607-1616.
18. Postow, M. A.,Sidlow, R.,Hellmann, M. D.(2018).Immune-related adverse events associated with immune checkpoint blockade.New England Journal of Medicine,378(2),158-168.
19. Postow, M., & Wolchok, J. (2018). Toxicities associated with checkpoint inhibitor immunotherapy. In M. E. Ross (Ed.), UpToDate. Retrieved from https://www.uptodate.com/contents/toxicities-associated-with-checkpoint-inhibitor-immunotherapy?search=Toxicities%20associated%20with%20checkpoint%20inhibitor%20immunotherapy&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
20. Ribas, A.,Hodi, F. S.,Callahan, M.,Konto, C.,Wolchok, J.(2013).Hepatotoxicity with combination of vemurafenib and ipilimumab.New England Journal of Medicine,368(14),1365-1366.
21. Ribas, A.,Kefford, R.,Marshall, M. A.,Punt, C. J.,Haanen, J. B.,Marmol, M.,Hauschild, A.(2013).Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.Journal of Clinical Oncology,31(5),616-622.
22. Sarnaik, A. A.,Yu, B.,Yu, D.,Morelli, D.,Hall, M.,Bogle, D.,Weber, J. S.(2011).Extended dose ipilimumab with a peptide vaccine: Immune correlates associated with clinical benefit in patients with resected high-risk stage IIIc/IV melanoma.Clinical Cancer Research,17(4),896-906.
23. Sharkey, R. M.,Goldenberg, D. M.(2006).Targeted therapy of cancer: New prospects for antibodies and immunoconjugates.A Cancer Journal for Clinicians,56(4),226-243.
24. Topalian, S. L.,Sznol, M.,McDermott, D. F.,Kluger, H. M.,Carvajal, R. D.,Sharfman, W. H.,Hodi, F. S.(2014).Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.Journal of Clinical Oncology,32(10),1020-1030.
25. Weber, J. S.,Dummer, R.,de Pril, V.,Lebbe, C.,Hodi, F. S.,Investigators, M. D. X.(2013).Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: Detailed safety analysis from a phase 3 trial in patients with advanced melanoma.Cancer,119(9),1675-1682.
26. Weber, J. S.,Kahler, K. C.,Hauschild, A.(2012).Management of immune-related adverse events and kinetics of response with ipilimumab.Journal of Clinical Oncology,30(21),2691-2697.
27. Weber, J. S.,Kudchadkar, R. R.,Yu, B.,Gallenstein, D.,Horak, C. E.,Inzunza, H. D.,Chen, Y. A.(2013).Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma.Journal of Clinical Oncology,31(34),4311-4318.
28. Wolchok, J. D.,Neyns, B.,Linette, G.,Negrier, S.,Lutzky, J.,Thomas, L.,Lebbe, C.(2010).Ipilimumab monotherapy in patients with pretreated advanced melanoma: A randomised, double-blind, multicentre, phase 2, dose-ranging study.The Lancet Oncology,11(2),155-164.
29. 衛生福利部國民健康署（2017年，12月27日）．104年癌症登記年報．取自https://www.hpa.gov.tw/Pages/ashx/File.ashx?FilePath=~/File/Attach/8084/File_7635.pdf [Ministry of Health and Welfare (2017, December 27). 104 Cancer Registry Annual Report. Retrieved from https://www.hpa.gov.tw/Pages/ashx/File.ashx?FilePath=~/File/Attach/8084/File_7635.pdf]

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