Radtke Kendra K, Bender Brendan C, Li Zao, Turner David C, Roy Sumedha, Belousov Anton, Li Chi-Chung
Genentech Inc., South San Francisco, California.
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Clin Cancer Res. 2025 Jan 17;31(2):245-257. doi: 10.1158/1078-0432.CCR-24-2247.
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 are crucial in T-BiSp development. Required hospitalization for seven of the nine approved T-BiSp and the need for clinical intervention in severe cases highlight the importance of mitigation strategies to reduce health care burden and improve patient outcomes. 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 used 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 a review of T-BiSp licensing applications and emerging data from conferences and publications.
细胞因子释放综合征（CRS）是T细胞疗法中常见的急性毒性反应，包括双特异性T细胞衔接抗体（T-BiSp）。有效的CRS管理和预防对于T-BiSp的研发至关重要。已获批的9种T-BiSp中有7种需要住院治疗，严重病例需要临床干预，这凸显了减轻策略对于减轻医疗负担和改善患者预后的重要性。在本综述中，我们讨论了关于CRS减轻、管理和预测的新证据。我们涵盖了剂量优化的不同策略、当前和新出现的（预）治疗策略、药物研发过程中使用的定量药理学工具，以及生物标志物和预测因素。通过对T-BiSp许可申请的回顾以及会议和出版物中的新数据，我们深入了解了递增给药和制剂对CRS的影响，以及CRS与细胞因子动力学和药物水平的关系。
