Cytokine release syndrome (CRS) is a common acute toxicity in T-cell therapies, including T-cell engaging bispecific antibodies (T-BiSp). Effective CRS management and prevention is crucial in T-BiSp development. Required hospitalization for 7 of the 9 approved T-BiSp and the need for clinical intervention in severe cases highlight the importance of mitigation strategies to reduce healthcare burden and improve patient outcome. In this review, we discuss the emerging evidence on CRS mitigation, management, and prediction. We cover different strategies for dose optimization, current and emerging (pre)treatment strategies, quantitative pharmacology tools employed during drug development, and biomarkers and predictive factors. Insights are gleaned on step-up dosing and formulation effects on CRS and CRS relationships with cytokine dynamics and drug levels gathered through review of T-BiSp licensing applications and emerging data from conferences and publications.

中文翻译：

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T 细胞结合双特异性抗体的细胞因子释放综合征的临床药理学：当前见解和药物开发策略


细胞因子释放综合征 （CRS） 是 T 细胞疗法中常见的急性毒性，包括 T 细胞结合双特异性抗体 （T-BiSp）。有效的 CRS 管理和预防在 T-BiSp 发展中至关重要。9 种批准的 T-BiSp 中有 7 种需要住院治疗，严重病例需要临床干预，这凸显了缓解策略对减轻医疗负担和改善患者预后的重要性。在本综述中，我们讨论了有关 CRS 缓解、管理和预测的新证据。我们涵盖了不同的剂量优化策略、当前和新兴的（前）治疗策略、药物开发过程中采用的定量药理学工具以及生物标志物和预测因素。通过回顾 T-BiSp 许可申请以及来自会议和出版物的新数据，收集了关于递增剂量和制剂对 CRS 和 CRS 与细胞因子动力学和药物水平的关系的见解。