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:Incorporating the Next Generation of Immunotherapies Into the Treatment of Multiple Myeloma.
Incorporating the Next Generation of Immunotherapies Into the Treatment of Multiple Myeloma.
免疫治疗近期改变了多发性骨髓瘤(MM)的治疗格局。
免疫疗法近来改变了多发性骨髓瘤(MM)的治疗格局。CAR T细胞和T细胞重定向双特异性抗体(BsAb)可使复发/难治性MM患者获得显著应答并延长生存。目前,美国FDA已批准2种靶向BCMA的CAR T细胞产品和4种BsAb(3种靶向BCMA,1种靶向GPRC5D)用于复发/难治性MM,且显示出明显疗效。这些药物目前正在早期治疗场景中接受评估,包括用于新诊断MM的一线治疗方案。需要特别注意的是,CAR T细胞疗法和BsAb的使用须谨慎管理其特有毒性,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、血细胞减少及感染风险升高。本综述总结MM免疫治疗的当前格局,并讨论CAR T细胞疗法与BsAb的序贯应用;还介绍评估新联合方案和治疗情境的在研临床试验。免疫疗法已成为MM治疗工具箱的重要组成部分,未来几年其作用有望进一步扩大。
Immunotherapies have recently changed the treatment landscape of multiple myeloma (MM). CAR T cells and T-cell-redirecting bispecific antibodies (BsAbs) yield impressive responses and extend survival in patients with relapsed/refractory MM. There are now 2 BCMA-directed CAR T-cell products and 4 BsAbs (3 targeting BCMA, 1 targeting GPRC5D) currently approved by the FDA for relapsed/refractory MM, in which they demonstrated considerable efficacy. These drugs are now being evaluated in early treatment settings, including as part of frontline regimens for newly diagnosed MM. Importantly, administration of CAR T-cell therapy and BsAbs necessitate careful attention to unique toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenias, and heightened infection risk. This review summarizes the current landscape of immunotherapy in MM, including perspectives on sequencing CAR T-cell therapy and BsAbs. It also discusses ongoing clinical trials evaluating immunotherapy in new combinations and treatment contexts. Immunotherapies have become a key component of the MM therapeutic armamentarium and are poised to assume an even larger role in the coming years.
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