Chimeric antigen receptor (CAR) T-cell therapies are highly effective for multiple myeloma (MM) but their impressive efficacy is associated with treatment-related neurotoxicities in some patients. In CARTITUDE-1, 5% of patients with MM reported movement and neurocognitive treatment-emergent adverse events (MNTs) with ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeted CAR T-cell therapy. We assessed the associated factors for MNTs in CARTITUDE-1. Based on common features, patients who experienced MNTs were characterized by the presence of a combination of at least two variables: high tumor burden, grade ≥2 cytokine release syndrome (CRS) or any grade immune effector cell-associated neurotoxicity syndrome (ICANS) after cilta-cel infusion, and high CAR T-cell expansion/persistence. Strategies were implemented across the cilta-cel development program to monitor and manage patients with MNTs, including enhanced bridging therapy to reduce baseline tumor burden, early aggressive treatment of CRS and ICANS, handwriting assessments for early symptom detection, and extended monitoring/reporting time for neurotoxicity beyond 100 days post-infusion. After successful implementation of these strategies, the incidence of MNTs was reduced from 5% to <1% across the cilta-cel program, supporting its favorable benefit–risk profile for treatment of MM.
嵌合抗原受体（CAR）T细胞疗法对多发性骨髓瘤（MM）具有显著疗效，但其卓越的治疗效果在某些患者中伴随治疗相关神经毒性。在CARTITUDE-1研究中，5%接受靶向B细胞成熟抗原的CAR-T细胞疗法——西达基奥仑赛治疗的MM患者报告了运动及神经认知治疗中出现的不良事件。我们评估了CARTITUDE-1研究中发生此类神经毒性事件的相关因素。根据共同特征分析，发生神经毒性的患者通常至少具备以下两种变量的组合：高肿瘤负荷、输注西达基奥仑赛后出现≥2级细胞因子释放综合征（CRS）或任何级别的免疫效应细胞相关神经毒性综合征（ICANS），以及CAR-T细胞的高扩增/高持久性。西达基奥仑赛研发项目组实施了系列策略以监测和管理神经毒性患者，包括：通过强化桥接治疗降低基线肿瘤负荷、对CRS和ICANS进行早期积极干预、通过书写评估实现早期症状识别，以及将神经毒性监测/报告时间延长至输注后100天以上。这些策略成功实施后，西达基奥仑赛整体项目的神经毒性发生率从5%降至1%以下，进一步支持了该疗法治疗多发性骨髓瘤的获益-风险优势。
肿瘤(癌症)患者之家