目的 探讨免疫检查点抑制剂相关不良反应的发生特点,为临床用药安全提供依据。方法 汇总整理我院2020年1月至2022年4月报告的免疫检查点抑制剂相关的不良反应病例进行分析和再评价。结果 25例免疫检查点抑制剂相关不良反应涉及药物包括卡瑞利珠单抗8例、信迪利单抗6例、替雷利珠单抗4例、度伐利尤单抗3例、帕博利珠单抗3例及纳武利尤单抗1例。其中严重程度为严重的13例(52%),一般的12例(48%)。25例报告中男性19例,女性6例,最小年龄26岁,最大年龄81岁,平均年龄(62.40±15.38)岁。原患疾病包括肺癌、骨肿瘤、食管癌、膀胱癌、肝癌及胰腺癌。不良反应临床表现以免疫相关肺炎、内分泌毒性及心脏毒性为主。药品不良反应(ADR)发生时间从用药当天到首次用药后329 d不等。结论 临床应关注免疫检查点抑制剂的安全性问题,只有妥善管理好免疫治疗相关不良反应,才能更好的实现肿瘤免疫治疗。
Abstract
OBJECTIVE To explore the characteristics of adverse reactions related to immune checkpoint inhibitors, and to provide reference for rational use of drugs. METHODS The adverse reaction cases related to immune checkpoint inhibitors reported in our hospital from January 2020 to April 2022 for analysis and re-evaluation were summarized Summarize the adverse reaction cases related to immune checkpoint inhibitors reported in our hospital from January 2020 to April 2022 for analysis and re-evaluation. RESULTS The 25 immune checkpoint inhibitor-related adverse reactions involved camrelizumab (8 cases), sintilimab (6 cases), tislelizumab (4 cases), durvalumab (3 cases), pembrolizumab (3 cases) and nivolumab (1 case). Among them, 13 cases (52%) were severe and 12 cases (48%) were normal. Among the 25 cases reported, there were 19 males and 6 females, the youngest age was 26 years old, the oldest age was 81 years old, and the average age was (62.40±15.38) years old. Primary diseases include lung cancer, bone tumor, esophageal cancer, bladder cancer, liver cancer and pancreatic cancer. The main clinical manifestations of adverse reactions were immune-related pneumonia, endocrine toxicity and cardiotoxicity. The occurrence time of ADR ranged from the day of administration to 329 days after the first administration. CONCLUSION Clinical attention should be paid to the safety of immune checkpoint inhibitors. Only by properly managing the adverse reactions related to immunotherapy can tumor immunotherapy be better achieved.
关键词
免疫检查点抑制剂 /
免疫治疗相关不良反应 /
安全用药
{{custom_keyword}} /
Key words
immune checkpoint inhibitor /
immune-related adverse event /
drug safety
{{custom_keyword}} /
中图分类号：
R95
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] SHARMA P, ALLISON J P. The future of immune checkpoint therapy. Science, 2015, 348(6230):56-61.
[2] WANG X, YUAN P, YUE J, et al. Clinical observation of adverse events of immune checkpoint inhibitors in 20 advanced tumor patients and literature reviews . Cancer Res Prev Treat(肿瘤防治研究), 2020, 47(6):427-430.
[3] GUANGDONG PHARMACEUTICAL ASSOCIATION. Guidelines for full-process pharmaceutical care for immune checkpoint inhibitors (2019 version) . Pharm Today(今日药学), 2020, 30(5):289-305.
[4] NI J, ZHANG L. Progress of immunotherapy related adverse events . Chin J Intern Med(中华内科杂志), 2021, 60(1):84-88.
[5] IMMUNOTHERAPY EXPERT COMMITTEE OF CHINESE SOCIETY OF CLINICAL ONCOLOGY. Expert consensus on the application of immune checkpoint inhibitors in special populations. Chin Clin Oncol(临床肿瘤学杂志), 2022, 27(5):442-454.
[6] GENERAL OFFICE OF THE NATIONAL HEALTH COMMISSION. Notice of the general office of the national health commission on issuing the guideline for the clinical application of new antitumor drugs (2021 Edition). (2021-12-20) . http://www.nhc.gov.cn/yzygj/s7659/202112/0fbf3f04092b4d67be3b3e89040d8489.shtml.
[7] LU S, LIU T S. Research progress on adverse events related to immune checkpoint inhibitors . Chin J Clin Med(中国临床医学), 2020, 27(6):903-906.
[8] POSTOW M A, SIDLOW R, HELLMANN M D. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med, 2018, 378(2):158-168.
[9] LUNG CANCER GROUP. RESPIRATORY MEDICINE BRANCH OF CHINESE MEDICAL ASSOCIATION. Expert consensus on diagnosis and treatment of immune checkpoint inhibitor-related pneumonia. Chin J Tuberc Respir Dis(中华结核和呼吸杂志), 2019, 42(11):820-824.
[10] FRIEDMAN C F, PROVERBS-SINGH T A, POSTOW M A. Treatment of the immune related adverse effects of immune checkpoint inhibitors: a review . JAMA Oncol, 2016, 2(10):1346-1353.
[11] ZHAO Q, QIU X H, CHEN L L, et al. Immunotherapy-induced pneumonitis after immune-check-point inhibitors therapy in patients with malignant tumor. J Chin Pract Diagn Ther(中华实用诊断与治疗杂志), 2020, 34(7):683-685.
[12] SU Q, ZHU E C, WU J B, et al. Risk of pneumonitis and pneumonia associated with immune checkpoint inhibitors for solid tumors: a systematic review and meta-analysis . Front Immunol, 2019, 10:108. Doi:10.3389/fimmu.2019.00108.
[13] IMMUNOENDOCRINOLOGY GROUP, ENDOCRINOLOGY SOCIETY OF CHINESE MEDICAL ASSOCIATION. Chinese expert consensus on the immune checkpoint inhibitors-induced endocrine immune-related adverse event(2020). Chin J Endocrinol Metab(中华内分泌代谢杂志), 2021, 37(1):1-14.
[14] BARROSO-SOUSA R, BARRY W T, GARRIDO-CASTRO A C, et al. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis. JAMA Oncol, 2018, 4(2): 173-182.
[15] LI HY, ZHANG M L, YAO Y H. Cardiotoxicity induced by immune checkpoint inhibitors . Chin Heart J(心脏杂志), 2020, 32(6):650-654.
[16] HEINZERLING L, OTT P A, HODI F S, et al. Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy. J Immunother Cancer, 2016, 4:50. Doi:10.1186/s40425-016-0152-y.
[17] KUMAR V, CHAUDHARY N, GARG M, et al. Corrigendum: current diagnosis and management of immune related adverse events(irAEs) induced by immune checkpoint inhibitor therapy. Front Pharmacol, 2017, 8 (8):49.
[18] PUZANOV I, DIAB A, ABDALLAH K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer, 2017, 5 (1):95.
[19] LI W Y, LI L C, HUO J G. Side effects and management in immunotherapy based on immune checkpoint inhibitors . World Chin J Digestol(世界华人消化杂志), 2018, 28(16):755-764.
[20] 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.
[21] HE Z, YE F, ZHANG G X. Advances in research on immune checkpoint inhibitors-related enterocolitis and gut microbiota. Chin J Gastroenterol(胃肠病学), 2020, 25(7):424-426.
[22] ZHOU H P, CHEN Y. Practice of pharmaceutical care in immune-associated pancreatitis caused by sintilimab by clinical pharmacists. Pharm Today(今日药学), 2021, 31(5):392-395.
[23] Chinese Society of Clinical Oncology. Immune Checkpoint Inhibitor-related Toxicity Management Guidelines(免疫检查点抑制剂相关的毒性管理指南). Beijing: People′s Medical Publishing House, 2019.
[24] SUPAKORNNUMPORN S, KATIRJI B. Guillain-Barré syndrome triggered by immune checkpoint inhibitors: a case repor t and literature reviewy. J Clin Neuromuscul Dis, 2017, 19(2):80-83.
[25] LIANG J, LI S S, ZHOU X X. Renal damage with immune checkpoint inhibitors. Chin J Clin Res(中国临床研究), 2021, 34(10):1420-1422.
[26] PETRELLI F, ARDITO R, BORGONOVO K, et al. Haematological toxicities with immunotherapy in patients with cancer: a systematic review and metaanalysis. Eur J Cancer, 2018, 103: 7-16. Doi:10.1016/j.ejca.2018.07.129.
[27] ZHONG Q F, ZHOU A P. Management of adverse reactions of immune checkpoint blockade . Chin New Drugs J(中国新药杂志), 2017, 26(7):825-829.
[28] ZHOU C C, WANG J, BU H, et al. Chinese experts consensus on immune checkpoint inhibitors for non-small cell lung cancer (2019 version) . Chin J Lung Cancer(中国肺癌杂志), 2020, 23(2):65-74.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(915 KB)
