CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Safety evaluation of axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma.
Safety evaluation of axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma.
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深入了解与靶向 CD19 的 CAR-T 细胞治疗相关的毒性,将有助于为该治疗优选患者。
引言:CD19靶向嵌合抗原受体(CAR)T细胞疗法对复发/难治性大B细胞淋巴瘤(LBCL)患者高度有效;目前已批准三种CD19 CAR-T 细胞产品用于该适应证:axicabtagene ciloleucel、tisagenlecleucel和lisocabtagene maraleucel。尽管CD19靶向CAR-T 细胞疗法具有临床获益,治疗期间出现的毒性仍可导致显著发病负担。综述范围:本文讨论axicabtagene ciloleucel用于LBCL患者的安全性问题,包括常见免疫介导毒性——细胞因子释放综合征和免疫效应细胞相关神经毒性综合征。
此外,还回顾CAR-T 细胞治疗相关血细胞减少、感染、器官功能障碍,以及近期描述的噬血细胞性淋巴组织细胞增多症。专家观点:全面了解CD19靶向CAR-T 细胞疗法相关毒性,有助于为该疗法优化患者选择。
此外,掌握CAR-T 相关并发症的预防措施、早期识别和适当干预,将有助于安全实施疗法,并最终改善患者结局。
INTRODUCTION: CD19-directed chimeric antigen receptor (CAR) T-cell therapy is a highly effective therapy for patients with relapsed/refractory large B-cell lymphoma (LBCL) and three CD19 CAR T-cell products (axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel) are currently approved for this indication.
Despite the clinical benefit of CD19 directed CAR T-cell therapy, this treatment is associated with significant morbidity from treatment-emergent toxicities. AREAS COVERED: This Review discusses the safety considerations of axicabtagene ciloleucel in patients with LBCL. This includes discussion of the frequently observed immune-mediated toxicities of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.
Additionally, we review CAR T-cell therapy related cytopenias, infection, organ dysfunction and the more recently described hemophagocytic lymphohistiocytosis. EXPERT OPINION: A thorough understanding of the toxicities associated with CD19-directed CAR T-cell therapy will facilitate the optimal selection of patients for this therapy.
Furthermore, knowledge of preventative measures of CAR T-cell related complications, and early recognition and appropriate intervention will lead to the safe administration of these therapies, and ultimately improved outcomes for our patients.
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