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 real-world outcomes of CD19-directed CAR T-cell therapies in large B-cell lymphoma.
Comparative real-world outcomes of CD19-directed CAR T-cell therapies in large B-cell lymphoma.
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目前有 3 种商业化 CD19 靶向 CAR-T 疗法可用于大 B 细胞淋巴瘤(LBCL),但尚无随机临床试验比较其疗效和安全性。本回顾性多中心队列研究评估复发/难治性 LBCL 患者接受 axicabtagene ciloleucel(axi-cel)、tisagenlecleucel(tisa-cel)或 lisocabtagene maraleucel(liso-cel)后的真实世界结局。2016 年 4 月至 2024 年 7 月,共 624 例患者接受 CD19 靶向 CAR-T:axi-cel 344 例、tisa-cel 142 例、liso-cel 138 例。中位随访 20.9 个月时,axi-cel、tisa-cel 和 liso-cel 的估计 2 年 PFS 率及 OS 率分别为 46% 和 63%、30% 和 45%、45% 和 58%。
多变量分析校正潜在混杂因素后,tisa-cel 与较 axi-cel 更差的 PFS 和 OS 相关;liso-cel 与 axi-cel 的生存差异无统计学意义。倾向评分及按二线与三线或后续治疗分层的亚组分析结果相似。与 axi-cel 相比,输注后 100 天 liso-cel 的 ORR 较高,tisa-cel 较低。axi-cel 的 CRS、免疫效应细胞相关神经毒性综合征、免疫效应细胞相关血液毒性和发热性中性粒细胞减少发生率显著较高,但感染或非复发死亡的累积发生率无显著差异。axi-cel 的静脉至静脉周转时间更短(axi-cel 35 天;tisa-cel 43 天;liso-cel 41 天),不符合规格产品更少(分别为 2%、4%、11%)。这些结果揭示了不同产品选择可能带来的结局差异。
Although 3 commercial CD19-targeted chimeric antigen receptor (CAR) T-cell therapies are available for large B-cell lymphomas (LBCLs), no randomized clinical trials have compared their efficacy and safety. In this retrospective multicenter cohort study, we evaluated real-world clinical outcomes of patients with relapsed/refractory LBCL treated with axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel). Between April 2016 and July 2024, 624 patients received CD19-targeted CAR T-cell therapies (344 axi-cel, 142 tisa-cel, and 138 liso-cel). At a median follow-up of 20. 9 months, the respective estimated 2-year progression-free survival (PFS) and overall survival (OS) rates were 46% and 63% for axi-cel, 30% and 45% for tisa-cel, and 45% and 58% for liso-cel.
After adjusting for potential confounders in multivariate analyses, tisa-cel was associated with inferior PFS and OS compared to axi-cel. No significant survival differences were found between liso-cel and axi-cel. Propensity score and subanalyses of patients treated in the second-line vs third-line or later settings yielded similar outcomes.
Compared to axi-cel, the objective response rate at 100 days was higher for liso-cel and lower for tisa-cel. Rates of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hematotoxicity, and febrile neutropenia were significantly higher with axi-cel.
However, no significant differences in the cumulative incidence of infections or nonrelapse mortality were found. Axi-cel was associated with faster vein-to-vein time (axi-cel, 35 days; tisa-cel, 43 days; liso-cel, 41 days) and fewer out-of-specification products (axi-cel, 2%; tisa-cel, 4%; liso-cel, 11%). These results provide insights into potential differential outcomes depending on product selection.
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