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:Chimeric antigen receptor T-cell therapy in aggressive lymphomas.
Chimeric antigen receptor T-cell therapy in aggressive lymphomas.
目前,三种靶向CD19的自体CAR T细胞疗法(axicabtagene ciloleucel、tisagenlecleucel和lisocabtagene maraleucel)已获批用于DLBCL的三线治疗,显示出高达40%的持久完全缓解率。
本综述提供了截至2025年4月嵌合抗原受体(CAR)T细胞疗法在弥漫性大B细胞淋巴瘤(DLBCL)中的最新进展,重点关注特定患者群体、长期毒性以及治疗的最佳序贯,特别是鉴于双特异性抗体等新兴治疗方法的出现。
目前,已有三种靶向CD19的自体CAR T细胞疗法(axicabtagene ciloleucel、tisagenlecleucel和lisocabtagene maraleucel)获批用于DLBCL的三线治疗,显示出高达40%的持久完全缓解率。最近,axicabtagene ciloleucel和lisocabtagene maraleucel已获批用于难治性或早期复发性DLBCL的二线治疗。此外,CD20/CD3双特异性抗体的出现扩大了复发/难治性DLBCL的治疗选择,引发了关于这些疗法最佳序贯方案的疑问。越来越多的真实世界证据进一步支持CAR T细胞疗法在特定人群中的疗效,包括老年患者、转化性惰性B细胞非霍奇金淋巴瘤患者以及Richter转化患者。最后,延长的随访期使人们能够更好地描述与CAR T细胞疗法相关的长期毒性。 总结:关于CAR T细胞疗法在DLBCL中的最新数据为其在特定人群中的获益、治疗序贯方案的优化以及长期毒性的管理提供了有价值的见解。
PURPOSE OF REVIEW: This review provides the latest update on chimeric antigen receptor (CAR) T-cell therapy in diffuse large B-cell lymphoma (DLBCL), as of April 2025, with a focus on specific patient populations, long-term toxicities, and the optimal sequencing of therapies, particularly in view of emerging treatments such as bispecific antibodies. RECENT FINDINGS: Currently, three autologous CAR T-cell therapies targeting CD19 (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) have been approved for third-line treatment of DLBCL, demonstrating durable complete remission rates of up to 40%. More recently, axicabtagene ciloleucel and lisocabtagene maraleucel have been approved for second-line therapy in refractory or early-relapsed DLBCL. Additionally, the emergence of CD20/CD3 bispecific antibodies has expanded therapeutic options for relapsed/refractory DLBCL, raising questions about the optimal sequencing of these therapies. Growing real-world evidence further supports the efficacy of CAR T-cell therapy in specific populations, including elderly patients, patients with transformed indolent B-cell non-Hodgkin lymphoma, and those with Richter's transformation. Finally, extended follow-up periods have allowed for a better characterization of the long-term toxicities associated with CAR T-cell therapy. SUMMARY: Recent data on CAR T-cell therapy in DLBCL provides valuable insights into its benefits for specific populations, the optimization of treatment sequencing, and the management of long-term toxicities.
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