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:Consensus recommendations on the management of toxicity associated with CD3×CD20 bispecific antibody therapy.
Consensus recommendations on the management of toxicity associated with CD3×CD20 bispecific antibody therapy.
靶向CD3和CD20的双特异性抗体(BsAb)是B细胞非霍奇金淋巴瘤患者治疗的新里程碑。
靶向CD3和CD20的双特异性抗体(BsAb)代表了B细胞非霍奇金淋巴瘤患者治疗的新里程碑。这些药物在重度经治患者中已展现出显著的单药活性,迄今已有3种药物在多个国家获得监管批准。然而,BsAb可能潜在导致与T细胞激活相关的严重毒性,尤其是细胞因子释放综合征(CRS)。这些即用型产品的预期广泛使用对实施提出了挑战,并凸显了在预见、减轻和管理不良事件方面提供指导的必要性。在临床试验中,针对BsAb治疗相关CRS和神经毒性的评估与处理指南,最初是仿照为嵌合抗原受体(CAR)T细胞疗法及其他免疫效应细胞疗法创建的算法而制定的,但BsAb与CAR T细胞疗法在毒性发生时间、性质和质量以及严重程度方面存在显著差异。因此,我们召集了一个由学术和社区实践医生、高级执业人员、注册护士和药剂师组成的国际专家组,这些成员在临床试验和试验外环境中具有使用CD3 CD20 BsAb的经验,以提供针对CD3 CD20 BsAb相关毒性评估和管理的全面、基于共识的建议。
Bispecific antibodies (BsAb) that target CD3 and CD20 represent a new milestone in the treatment of patients with B-cell non-Hodgkin lymphoma. These drugs have demonstrated remarkable single-agent activity in patients with heavily pretreated disease, and 3 drugs have so far received regulatory approvals in various countries. However, BsAbs can potentially lead to severe toxicity associated with T-cell activation, particularly cytokine release syndrome (CRS). The anticipated widespread use of these off-the-shelf products poses challenges for implementation and highlights the need for guidance in anticipating, mitigating, and managing adverse events. In clinical trials, guidance for the evaluation and treatment of CRS and neurotoxicity associated with BsAb therapy has been modeled after algorithms originally created for chimeric antigen receptor (CAR) T-cell therapies and other immune effector therapies, yet notable differences in timing, quality, and severity exist between the toxicities of BsAbs and CAR T-cell therapies. We therefore convened an international panel of academic and community practice physicians, advanced practitioners, registered nurses, and pharmacists with experience using CD3 CD20 BsAbs in clinical trial and off-trial settings to provide comprehensive, consensus-based recommendations specific to the assessment and management of CD3 CD20 BsAb-related toxicities.
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