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:Comparative Analysis of Bispecific Antibodies and CAR T-Cell Therapy in Follicular Lymphoma.
Comparative Analysis of Bispecific Antibodies and CAR T-Cell Therapy in Follicular Lymphoma.
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复发/难治性滤泡性淋巴瘤(RR-FL)的治疗格局中,CAR-T 细胞疗法与双特异性抗体(BsAb)之间存在关键选择。尽管CAR-T 疗法和BsAb靶向相似的免疫生物学机制及分子标志物,但缺乏直接临床试验比较,妨碍了对二者疗效进行比较。ZUMA-5等关键试验凸显了阿基仑赛(axi-cel)治疗RR-FL的疗效:完全缓解率为79%,缓解持续时间中位数超过3年。同样,TRANSCEND FL研究中利基迈仑赛(liso-cel)的完全缓解率为94%,在经多线治疗的患者中显示出稳健疗效。在BsAb中,mosunetuzumab在GO29781试验中显示出前景,在经多线治疗的RR-FL患者中总缓解率为62%。
因此,CAR-T 疗法通过单次输注有望带来治愈性获益,但其疗效受到CRS、神经毒性和血细胞减少等显著不良事件的制约,需要专门管理和监测患者。相比之下,BsAb耐受性更佳,但总缓解率较低且需频繁给药。鉴于两种疗法的疗效和安全性特征各异,个体化治疗策略至关重要。评估成本效益时,需结合临床结局和生活质量改善情况考量。成本效益分析不可或缺:CAR-T 疗法初始费用较高,但其带来长期缓解的潜力可能抵消重复治疗或住院相关支出。未来对耐药机制和最佳治疗顺序的研究,将进一步优化RR-FL治疗策略。
The treatment landscape for relapsed/refractory follicular lymphoma (RR-FL) is marked by a pivotal debate between chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs). While both CAR-T therapy and BsAbs target similar immunobiology and molecular markers, their efficacy comparisons are hindered by the lack of direct clinical trial comparisons.
Key trials, such as the ZUMA-5 study, underscore axicabtagene ciloleucel (axi-cel)'s efficacy in treating RR-FL, achieving a 79% complete response rate with a median duration of response exceeding 3 years. Similarly, lisocabtagene maraleucel (liso-cel) in the TRANSCEND FL study reports a 94% complete response rate, emphasizing robust outcomes in heavily pretreated patients. Among BsAbs, mosunetuzumab showed promise in the GO29781 trial, with a 62% overall response rate in heavily pretreated RR-FL patients.
Thus, CAR-T therapy offers potential curative benefits with a single infusion.
However, its efficacy is tempered by significant adverse events such as cytokine release syndrome (CRS), neurotoxicity, and cytopenias, requiring specialized management and patient monitoring. In contrast, BsAbs provide a more tolerable treatment option counterbalancing by lower response rates and frequent dosing requirements. Personalized treatment strategies are crucial because of these distinct efficacy and safety profiles.
When considering cost-effectiveness, both therapies need to be evaluated in the context of their clinical outcomes and quality of life improvements. Cost-effectiveness considerations are essential; while CAR-T therapies incur higher initial costs, their potential for long-term remission may mitigate expenses associated with repeated treatments or hospitalizations. Future research into resistance mechanisms and optimal therapeutic sequencing will further refine RR-FL management strategies.
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