Dana-Farber Cancer Institute, Boston, MA.
Mission Cancer and Blood, Des Moines, IA.
Blood. 2024 Apr 18;143(16):1565-1575. doi: 10.1182/blood.2023022432.
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.
双特异性抗体(BsAb)靶向 CD3 和 CD20,代表了治疗 B 细胞非霍奇金淋巴瘤患者的新里程碑。这些药物在经过大量预处理的疾病患者中表现出显著的单药活性,迄今为止已有 3 种药物在各国获得监管批准。然而,BsAb 可能导致与 T 细胞激活相关的严重毒性,特别是细胞因子释放综合征(CRS)。这些现成产品的预期广泛使用给实施带来了挑战,并强调了在预测、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,评估和治疗 BsAb 治疗相关 CRS 和神经毒性的指南是根据最初为嵌合抗原受体(CAR)T 细胞疗法和其他免疫效应疗法制定的算法建模的,但 BsAb 和 CAR T 细胞疗法的毒性之间存在明显的时间、质量和严重程度差异。因此,我们召集了一个由具有使用 CD3×CD20 BsAb 进行临床试验和非试验环境经验的学术和社区实践医生、高级从业者、注册护士和药剂师组成的国际小组,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。