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:Remission conversion drives outcomes after CAR T-cell therapy for multiple myeloma: a registry analysis from the DRST.
Remission conversion drives outcomes after CAR T-cell therapy for multiple myeloma: a registry analysis from the DRST.
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靶向B细胞成熟抗原的细胞疗法在对照临床试验中已显示出前景,但其在更广泛、多样化患者群体中的影响仍未得到充分探索。本研究考察了343例既往接受过三线治疗暴露的复发/难治性多发性骨髓瘤患者的真实世界疗效和安全性,这些患者在德国接受了idecabtagene vicleucel(ide-cel;n = 266)或ciltacabtagene autoleucel(cilta-cel;n = 77)治疗,且既往治疗线数>3。与ide-cel相比,cilta-cel表现出更优的结局,获得了更高的总缓解率(94% vs 82%)和10个月无进展生存期(PFS;76% vs 47%)。
cilta-cel还带来了更高的完全缓解(CR;61% vs 39%)和改善的缓解转化,更多患者在开始CAR-T 细胞治疗前未达到CR,而在治疗后达到CR。对于治疗后达到CR的患者,cilta-cel显示出更长的PFS,尤其是在以部分缓解或更差疗效进入治疗的患者中。细胞因子释放综合征在85%的cilta-cel病例和81%的ide-cel病例中观察到,主要为低级别。免疫效应细胞相关神经毒性综合征在cilta-cel中更常见(25% vs 15%),尽管10个月非复发死亡率在两种疗法之间相当(7% vs 5%)。倾向评分匹配后的加权多变量分析证实,cilta-cel在PFS方面具有显著优势,风险比为0.48。
总体而言,我们的注册分析中的结局与促成各自药物获批的关键试验相当。cilta-cel表现出更强的缓解转化和持久缓解能力。这些发现强调了需要个体化选择CAR-T 疗法以优化患者结局。
Cellular therapies targeting B-cell maturation antigen have shown promise in controlled clinical trials, but their impact in broader, diverse patient populations remains underexplored.
This study examines the real-world efficacy and safety in 343 triple-class-exposed patients with relapsed and refractory multiple myeloma who received idecabtagene vicleucel (ide-cel; n = 266) or ciltacabtagene autoleucel (cilta-cel; n = 77) after >3 previous lines of therapy in Germany. Cilta-cel, compared with ide-cel, demonstrated superior outcomes, achieving a higher overall response rate (94% vs 82%) and 10-month progression-free survival (PFS; 76% vs 47%). Cilta-cel also led to higher complete response (CR; 61% vs 39%) and improved response conversion, with more patients achieving CR after starting from less than CR before chimeric antigen receptor T-cell (CAR T) therapy.
For those attaining CR after therapy, cilta-cel showed longer PFS, especially in patients who entered treatment with a partial response or worse. Cytokine release syndrome was observed in 85% of cilta-cel and 81% of ide-cel cases, predominantly low grade.
Immune effector cell-associated neurotoxicity syndrome was more common with cilta-cel (25% vs 15%), although nonrelapse mortality at 10 months was comparable between therapies (7% vs 5%). Weighted multivariable analysis after propensity score matching confirmed a significant advantage in terms of PFS for cilta-cel, with a hazard ratio of 0. 48.
Overall, outcomes in our registry analysis were comparable with the pivotal trials that led to approval of the respective agents. Cilta-cel demonstrated a greater capacity for response conversion and durable remission.
These findings underscore the need for individualized CAR T therapy selection to optimize patient outcomes.
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