CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Post-progression outcomes following BCMA-directed CAR T-cell therapy in myeloma: impact of extramedullary and paramedullary disease.
Post-progression outcomes following BCMA-directed CAR T-cell therapy in myeloma: impact of extramedullary and paramedullary disease.
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我们的研究结果强调,MM 中 CAR-T 细胞治疗后的疾病进展具有异质性,EMD 预示着不良预后,凸显了影像学监测的迫切需求。旨在 CAR-T 细胞输注前减轻肿瘤负荷的桥接治疗或 CAR-T 细胞治疗后的维持治疗等策略值得进一步研究,以优化这一高危人群的缓解率并改善长期生存。
BCMA靶向CAR-T 细胞疗法改善了复发/难治性多发性骨髓瘤(MM)的结局;然而,大多数患者在治疗后1至3年内复发。CAR-T 细胞疗法后疾病进展的管理仍然是一项重大挑战,尤其是在包括髓外疾病(EMD)和旁髓疾病(PMD)在内的侵袭性亚型中。关于CAR-T 细胞疗法后进展模式以及EMD或PMD对CAR-T 细胞疗法后复发患者结局影响的真实世界数据仍然匮乏。
在这项单中心回顾性研究中,我们评估了2021年5月至2023年12月期间106例在接受商业化CAR-T 细胞疗法(ide-cel或cilta-cel)后进展的MM患者的进展模式和生存结局。OS定义为从CAR-T 细胞疗法后进展至死亡或末次随访的时间,PFS定义为从CAR-T 细胞疗法后进展至下一线治疗进展的时间。
82%的患者发生生化复发,进展时51%存在EMD或PMD。33%的患者在CAR-T 细胞输注时检测到基线EMD,与无EMD者相比,其PFS(3.6 vs. 7.0个月,p=0.0076)和OS(4.8 vs. 21.0个月,p=0.00086)显著更差。同样,进展时存在EMD与更短的PFS(4.7 vs. 8.5个月,p=0.022)和OS(7.4 vs. 21.1个月,p=0.035)相关。基线和进展时均为EMD阳性的患者结局最差。基线或进展时PMD与更差的生存无显著相关。
In this single-center, retrospective study, we evaluated progression patterns and survival outcomes in 106 MM patients who progressed after commercial CAR T-cell therapy (ide-cel or cilta-cel) between May 2021 and December 2023. Overall survival (OS) was defined from the time of post-CAR T-cell therapy progression to death or last follow-up, and progression-free survival (PFS) from post-CAR T-cell therapy progression to progression on the next line of therapy.
Biochemical relapse occurred in 82% of patients, with EMD or PMD present in 51% at progression. Baseline EMD at the time of CAR T-cell infusion was detected in 33% of patients and was associated with significantly inferior PFS (3.6 vs. 7.0 months, p=0.0076) and OS (4.8 vs. 21.0 months, p=0.00086) compared to those without EMD. Similarly, the presence of EMD at progression was associated with shorter PFS (4.7 vs. 8.5 months, p=0.022) and OS (7.4 vs. 21.1 months, p=0.035). Patients who were EMD positive at both baseline and progression had the poorest outcomes. PMD at baseline or progression was not significantly associated with worse survival. DISCUSSION: Our findings highlight that post-CAR T-cell progression in MM is heterogeneous and that EMD confers an adverse prognosis, emphasizing the critical need for imaging surveillance. Strategies such as bridging therapies aimed at reducing tumor burden prior to CAR T-cell infusion or maintenance therapies post-CAR T-cell therapy warrant further investigation to optimize responses and improve long-term survival in this high-risk population.
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