{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:04:18Z","timestamp":1787501058266,"version":"build-2736575974"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81670199"],"award-info":[{"award-number":["81670199"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81720108002"],"award-info":[{"award-number":["81720108002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"crossref","award":["2018ZX09734007"],"award-info":[{"award-number":["2018ZX09734007"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Jiangsu Province\u2019s Medical Elite Program","award":["ZDRCA2016015"],"award-info":[{"award-number":["ZDRCA2016015"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cytokine release syndrome (CRS) is the most common toxicity induced by chimeric antigen receptor (CAR) T cell therapy. At present, anti-IL-6 agents including tocilizumab and siltuximab have been applied in the treatment of CRS. However, tocilizumab and siltuximab are expensive and some patients fail to respond to anti-IL-6 therapy, which urges the need for new drugs. In clinical practice, we found some patients with multiple myeloma developed markedly increased levels of tumor necrosis factor (TNF)- \u03b1 during the CRS period after anti-BCMA CAR T cell infusion. Here we present the successful use of TNF-\u03b1 inhibitor (etanercept) to cure CRS in three patients. The introduction of etanercept did not alter patients' response to CAR T cell therapy and no adverse event was observed directly related to the administration of etanercept. Furthermore, in vitro experiments confirmed that etanercept did not affect the proliferation and effector function of CAR T cells. Our results indicate that etanercept could be considered as a treatment option for CRS in patients with significantly elevated TNF-\u03b1 levels.<\/jats:p>","DOI":"10.1186\/s40164-021-00209-2","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T15:06:31Z","timestamp":1613833591000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Etanercept as a new therapeutic option for cytokine release syndrome following chimeric antigen receptor T cell therapy"],"prefix":"10.1186","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3176-4922","authenticated-orcid":false,"given":"Lina","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6497-1194","authenticated-orcid":false,"given":"Lijuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"key":"209_CR1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s13045-018-0653-x","volume":"11","author":"D Liu","year":"2018","unstructured":"Liu D, Zhao J. Cytokine release syndrome: grading, modeling, and new therapy. J Hematol Oncol. 2018;11:121.","journal-title":"J Hematol Oncol"},{"key":"209_CR2","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nrclinonc.2017.148","volume":"15","author":"SS Neelapu","year":"2018","unstructured":"Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15:47\u201362.","journal-title":"Nat Rev Clin Oncol"},{"key":"209_CR3","unstructured":"Thompson JA, Schneider BJ, Brahmer J, Andrews S, Armand P, Bhatia S, et al. NCCN Guidelines Insights: Management of Immunotherapy-Related Toxicities, Version 1.2020. J Natl Compr Canc Netw. 2020;18:230\u201341."},{"key":"209_CR4","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.clml.2020.04.020","volume":"20","author":"SS Jatiani","year":"2020","unstructured":"Jatiani SS, Aleman A, Madduri D, Chari A, Cho HJ, Richard S, et al. Myeloma CAR-T CRS Management With IL-1R Antagonist Anakinra. Clin Lymphoma Myeloma Leuk. 2020;20:632\u20136.","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"209_CR5","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1182\/blood-2018-10-881722","volume":"133","author":"RM Sterner","year":"2019","unstructured":"Sterner RM, Sakemura R, Cox MJ, Yang N, Khadka RH, Forsman CL, et al. GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts. Blood. 2019;133:697\u2013709.","journal-title":"Blood"},{"key":"209_CR6","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1158\/1078-0432.CCR-18-1379","volume":"25","author":"X Xiao","year":"2019","unstructured":"Xiao X, He X, Li Q, Zhang H, Meng J, Jiang Y, et al. Plasma Exchange Can Be an Alternative Therapeutic Modality for Severe Cytokine Release Syndrome after Chimeric Antigen Receptor-T Cell Infusion: A Case Report. Clin Cancer Res. 2019;25:29\u201334.","journal-title":"Clin Cancer Res"},{"key":"209_CR7","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1182\/blood-2014-05-552729","volume":"124","author":"DW Lee","year":"2014","unstructured":"Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124:188\u201395.","journal-title":"Blood"},{"key":"209_CR8","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.cyto.2016.08.014","volume":"101","author":"H Mitoma","year":"2018","unstructured":"Mitoma H, Horiuchi T, Tsukamoto H, Ueda N. Molecular mechanisms of action of anti-TNF-\u03b1 agents - Comparison among therapeutic TNF-\u03b1 antagonists. Cytokine. 2018;101:56\u201363.","journal-title":"Cytokine"},{"key":"209_CR9","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1111\/bjh.16623","volume":"191","author":"J Wang","year":"2020","unstructured":"Wang J, Mou N, Yang Z, Li Q, Jiang Y, Meng J, et al. Efficacy and safety of humanized anti-CD19-CAR-T therapy following intensive lymphodepleting chemotherapy for refractory\/relapsed B acute lymphoblastic leukaemia. Br J Haematol. 2020;191:212\u201322.","journal-title":"Br J Haematol"},{"key":"209_CR10","doi-asserted-by":"crossref","unstructured":"Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117: 244\u201379.","DOI":"10.1016\/j.pharmthera.2007.10.001"}],"container-title":["Experimental Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-021-00209-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s40164-021-00209-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-021-00209-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T15:14:33Z","timestamp":1613834073000},"score":1,"resource":{"primary":{"URL":"https:\/\/ehoonline.biomedcentral.com\/articles\/10.1186\/s40164-021-00209-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,19]]},"references-count":10,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["209"],"URL":"https:\/\/doi.org\/10.1186\/s40164-021-00209-2","relation":{},"ISSN":["2162-3619"],"issn-type":[{"value":"2162-3619","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,19]]},"assertion":[{"value":"16 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was approved by the institutional review boards of the First Affiliated Hospital of Nanjing Medical University Ethics Committee. Informed consent was obtained from all patients for the treatment protocol.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Informed consent for research and publication from the patients was obtained.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16"}}