Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Division of Rheumatology, Massachusetts General Hospital, Boston, MA, USA.
Expert Opin Pharmacother. 2024 Feb;25(3):263-279. doi: 10.1080/14656566.2024.2340738. Epub 2024 Apr 10.
INTRODUCTION: Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of multiple hematologic malignancies. Engineered cellular therapies now offer similar hope to transform the management of solid tumors and autoimmune diseases. However, toxicities can be serious and often require hospitalization. AREAS COVERED: We review the two chief toxicities of CAR T therapy, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and the rarer immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. We discuss treatment paradigms and promising future pharmacologic strategies. Literature and therapies reviewed were identified by PubMed search, cited references therein, and review of registered trials. EXPERT OPINION: Management of CRS and ICANS has improved, aided by consensus definitions and guidelines that facilitate recognition and timely intervention. Further data will define optimal timing of tocilizumab and corticosteroids, current foundations of management. Pathophysiologic understanding has inspired off-label use of IL-1 receptor antagonism, IFNγ and IL-6 neutralizing antibodies, and janus kinase inhibitors, with data emerging from ongoing clinical trials. Further strategies to reduce toxicities include novel pharmacologic targets and safety features engineered into CAR T cells themselves. As these potentially curative therapies are used earlier in oncologic therapy and even in non-oncologic indications, effective accessible strategies to manage toxicities are critical.
简介:嵌合抗原受体 (CAR) T 细胞彻底改变了多种血液恶性肿瘤的治疗方法。现已设计出的细胞疗法同样有望改变实体瘤和自身免疫性疾病的治疗管理模式。然而,这些疗法可能具有严重毒性,且通常需要住院治疗。
涵盖领域:我们回顾了 CAR T 疗法的两种主要毒性,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),以及罕见的免疫效应细胞相关噬血细胞性淋巴组织细胞增多症样综合征。我们讨论了治疗方案和有前途的未来药物治疗策略。文献和治疗方法通过 PubMed 搜索、其中的参考文献以及已注册试验的综述进行了确定。
专家意见:CRS 和 ICANS 的管理得到了改善,这得益于共识定义和指南的帮助,这些定义和指南有助于识别和及时干预。进一步的数据将确定托珠单抗和皮质类固醇的最佳时机,目前这是管理的基础。病理生理学的理解激发了白细胞介素 1 受体拮抗剂、IFNγ 和白细胞介素 6 中和抗体以及 Janus 激酶抑制剂的应用,这些药物正在进行的临床试验中涌现。进一步降低毒性的策略包括针对 CAR T 细胞本身的新型药物靶点和安全特性。由于这些潜在的治愈性疗法更早地应用于肿瘤治疗,甚至应用于非肿瘤适应证,因此,管理毒性的有效、可及的策略至关重要。
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