决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Balancing Efficacy and Safety in Multiple Myeloma Patients Receiving B cell Maturation Antigen-Directed CAR T-Cell Therapy.
靶向 B 细胞成熟抗原(BCMA)的 CAR T 细胞疗法已成为复发/难治性多发性骨髓瘤患者的一种创新且有效的治疗,显示出高缓解率和持久缓解。
靶向 B 细胞成熟抗原(BCMA)的 CAR-T 细胞疗法已成为复发/难治性多发性骨髓瘤患者的一种创新且有效的治疗方式,可带来较高应答率和持久缓解。但其使用伴随广泛毒性,既有特征明确的常见事件,也有较罕见、描述较少的并发症。全面了解常见和罕见毒性,对于及时识别和处理、预防非复发死亡至关重要。常见毒性包括细胞因子释放综合征、免疫效应细胞相关神经毒性综合征(ICANS)、免疫效应细胞相关血液毒性和感染。此外也报告了发生率较低的不良事件,包括非 ICANS 神经毒性(如帕金森样运动障碍)、免疫介导性肠结肠炎、噬血细胞性淋巴组织细胞增多症和继发恶性肿瘤。毒性发生时间和严重程度各异,可能受 CAR-T 细胞扩增和持续程度及患者个体因素影响。本综述总结目前已获批 BCMA 靶向 CAR-T 疗法安全性特征的证据,重点介绍常见和罕见毒性、可能机制及管理策略。
B-cell maturation antigen (BCMA) directed CAR T-cell therapy has emerged as an innovative and effective treatment for patients with relapsed/refractory multiple myeloma, demonstrating high response rates and durable remissions. However, its use is associated with a broad spectrum of toxicities, ranging from well characterized common events to rarer, less well described complications. A comprehensive understanding of both common and rare toxicities is essential for timely recognition and management to prevent non-relapse mortality. Frequently observed toxicities include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity, and infections. In addition, less frequent adverse events have been reported, including non-ICANS neurotoxicity such as parkinsonian-like movement disorders, immune-mediated enterocolitis, hemophagocytic lymphohistiocytosis, and secondary malignancies. The timing and severity of these toxicities is variable and may be influenced by the extent of CAR T-cell expansion and persistence, as well as patient-specific factors. In this review, we summarize currently available evidence with respect to the safety profile of approved BCMA-targeted CAR T-cell therapies, emphasizing both common and rare toxicities, their possible underlying mechanisms, and management strategies.
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