How I treat refractory CRS and ICANS after CAR T-cell therapy.
How I treat refractory CRS and ICANS after CAR T-cell therapy.
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DOI：
10.1182/blood.2022017414
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发表时间：
2023-05-18
期刊：
影响因子：
20.3
通讯作者：
Shah, Nirali N.
中科院分区：
文献类型：
--
作者：
Jain, Michael D.;Smith, Melody;Shah, Nirali N.
随着标准治疗适应症的扩大和新研究产品的开发，嵌合抗原受体(CAR)T细胞疗法的临床应用正在迅速增长。建立细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)的共识诊断标准，以及稳定使用tocilizumab和皮质类固醇治疗，对于促进其广泛使用至关重要。预防更严重毒副作用的先发制人干预提高了安全性，促进了医学虚弱人群和严重CRS/ICAN高危人群的CAR T细胞治疗。尽管如此，持续性或进展性CRS和ICAN的发展仍然是有问题的，因为它损害了患者的预后，并且治疗起来具有挑战性。在这个以病例为基础的讨论中，我们重点介绍了一系列对一线干预措施难以奏效的CRS和/或ICAN病例。我们讨论了我们的方法来管理持续或进展超过最初的tocilizumab或皮质类固醇治疗的难治性毒性，描述了严重毒性的危险因素，强调了Anakinra的新使用，并回顾了缓解策略和支持性护理措施，以改善发展这些难治性毒性的患者的预后。随着6种嵌合抗原受体(CAR)T细胞产品获得美国食品和药物管理局(FDA)的批准，以及更多产品在临床试验中表现出希望，血液学家需要意识到具有挑战性的并发症，并知道如何在常规实践中处理这些并发症。由副主编Helen E.Heslop介绍，这本How I Treat系列文章重点介绍了几个关键的并发症，回顾了目前对其病因的理解，并通过对说明性病例的讨论提供了治疗指导。
The clinical use of chimeric antigen receptor (CAR) T-cell therapy is growing rapidly because of the expanding indications for standard-of-care treatment and the development of new investigational products. The establishment of consensus diagnostic criteria for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), alongside the steady use of both tocilizumab and corticosteroids for treatment, have been essential in facilitating the widespread use. Preemptive interventions to prevent more severe toxicities have improved safety, facilitating CAR T-cell therapy in medically frail populations and in those at high risk of severe CRS/ICANS. Nonetheless, the development of persistent or progressive CRS and ICANS remains problematic because it impairs patient outcomes and is challenging to treat. In this case-based discussion, we highlight a series of cases of CRS and/or ICANS refractory to front-line interventions. We discuss our approach to managing refractory toxicities that persist or progress beyond initial tocilizumab or corticosteroid administration, delineate risk factors for severe toxicities, highlight the emerging use of anakinra, and review mitigation strategies and supportive care measures to improve outcomes in patients who develop these refractory toxicities. With 6 chimeric antigen receptor (CAR) T-cell products approved by the US Food and Drug Administration and many more showing promise in clinical trials, the need for hematologists to be aware of challenging complications and know how to manage them in routine practice is paramount. Introduced by Associate Editor Helen E. Heslop, this How I Treat series highlights several key complications, reviews current understanding of their etiologies, and provides guidance on therapies through discussion of illustrative cases.
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影响因子：
82.9
作者：
Bachy, Emmanuel;Le Gouill, Steven;Di Blasi, Roberta;Sesques, Pierre;Manson, Guillaume;Cartron, Guillaume;Beauvais, David;Roulin, Louise;Gros, Francois Xavier;Rubio, Marie Therese;Bories, Pierre;Bay, Jacques Olivier;Llorente, Cristina Castilla;Choquet, Sylvain;Casasnovas, Rene-Olivier;Mohty, Mohamad;Guidez, Stephanie;Joris, Magalie;Loschi, Michael;Carras, Sylvain;Abraham, Julie;Chauchet, Adrien;La Rochelle, Laurianne Drieu;Deau-Fischer, Benedicte;Hermine, Olivier;Gastinne, Thomas;Tudesq, Jean Jacques;Gat, Elodie;Broussais, Florence;Thieblemont, Catherine;Houot, Roch;Morschhauser, Franck
通讯作者：
Morschhauser, Franck
影响因子：
12.8
作者：
Cohen AD;Parekh S;Santomasso BD;Gállego Pérez-Larraya J;van de Donk NWCJ;Arnulf B;Mateos MV;Lendvai N;Jackson CC;De Braganca KC;Schecter JM;Marquez L;Lee E;Cornax I;Zudaire E;Li C;Olyslager Y;Madduri D;Varsos H;Pacaud L;Akram M;Geng D;Jakubowiak A;Einsele H;Jagannath S
通讯作者：
Jagannath S
影响因子：
8.8
作者：
Fitzgerald JC;Weiss SL;Maude SL;Barrett DM;Lacey SF;Melenhorst JJ;Shaw P;Berg RA;June CH;Porter DL;Frey NV;Grupp SA;Teachey DT
通讯作者：
Teachey DT
DOI：
10.1158/1078-0432.ccr-20-1434
发表时间：
2020-09-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Faramand R;Jain M;Staedtke V;Kotani H;Bai R;Reid K;Lee SB;Spitler K;Wang X;Cao B;Pinilla J;Lazaryan A;Khimani F;Shah B;Chavez JC;Nishihori T;Mishra A;Mullinax J;Gonzalez R;Hussaini M;Dam M;Brandjes BD;Bachmeier CA;Anasetti C;Locke FL;Davila ML
通讯作者：
Davila ML
影响因子：
168.9
作者：
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通讯作者：
Siddiqi, Tanya