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:Real-world comparison of lisocabtagene maraleucel and axicabtagene ciloleucel in large B-cell lymphoma: an inverse probability of treatment weighting analysis with 3-year follow-up.
Real-world comparison of lisocabtagene maraleucel and axicabtagene ciloleucel in large B-cell lymphoma: an inverse probability of treatment weighting analysis with 3-year follow-up.
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Lisocabtagene maraleucel (liso-cel) 和 axicabtagene ciloleucel (axi-cel) 是美国食品药品监督管理局和欧洲药品管理局批准的嵌合抗原受体 (CAR) T 细胞疗法,用于治疗复发/难治性大 B 细胞淋巴瘤 (LBCL)。
然而,缺乏对其功效和毒性以及长期随访的现实世界比较分析。我们对 Fred Hutchinson 癌症中心的 160 名 LBCL 患者进行了一项回顾性研究,这些患者按照标准护理使用商业 lisocel 或 axi-cel 进行治疗。
我们使用治疗加权逆概率 (IPTW) 来减轻治疗分配偏差和多变量调整以尽量减少其他混杂来源,评估了 CAR-T 细胞产品类型对结果的影响。Axi-cel 与细胞因子释放综合征(CRS;[G]1+ 级:调整比值比 [aOR] =4.27;P=0.004;G2+:aOR=2.88;P=0.006)、免疫效应细胞相关神经毒性综合征(ICANS;G1+:aOR=2.10;P=0.048)和免疫效应细胞相关血液毒性发生率显着升高相关。(ICAHT;G1+:aOR=8.09;P<0.001;G2+:aOR=3.86;P=0.001)。Axi-cel 还与更频繁地使用支持性护理措施相关,例如托珠单抗(aOR=2.50;P=0.017)、地塞米松(aOR=2.77;P=0.007)和头孢吡肟(aOR=3.37;P=0.001)。
我们无法确认 liso-cel 与 axi-cel 治疗后的缓解率和生存结果有统计学上的显着差异(完全缓解:aOR=1.12;P=0.8;总生存期:调整后风险比 [aHR]=1.34;P=0.3;无进展生存期:aHR=0.97;P=0.9;缓解持续时间:aHR=0.89;P=0.7;累计复发率:aHR=0.92; P=0.8)。
总之,虽然 axicel 与需要更强化管理的更大毒性相关,但 axi-cel 和 liso-cel 之间的缓解率和生存结果相当。
Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are Food and Drug Administration- and European Medicines Agency-approved chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory large B-cell lymphoma (LBCL).
However, comparative real-world analyses of their efficacy and toxicity with extended follow-up are lacking.
We conducted a retrospective study of 160 LBCL patients treated at the Fred Hutchinson Cancer Center with commercial liso- cel or axi-cel per standard of care. Using inverse probability of treatment weighting (IPTW) to mitigate treatment allocation bias and multivariable adjustments to minimize other sources of confounding, we assessed the impact of CAR T-cell product type on outcomes. Axi-cel was associated with significantly higher rates of cytokine release syndrome (CRS; grade [G]1+: adjusted odds ratio [aOR] =4.
27; P=0. 004; G2+: aOR=2. 88; P=0. 006), immune effector cell-associated neurotoxicity syndrome (ICANS; G1+: aOR=2. 10; P=0. 048), and immune effector cell-associated hematotoxicity (ICAHT; G1+: aOR=8. 09; P<0. 001; G2+: aOR=3. 86; P=0. 001). Axi-cel was also associated with more frequent use of supportive care measures, such as tocilizumab (aOR=2. 50; P=0. 017), dexamethasone (aOR=2. 77; P=0. 007), and cefepime (aOR=3. 37; P=0. 001).
We could not confirm statistically significant differences in the response rates and survival outcomes after liso-cel versus axi-cel (complete response: aOR=1. 12; P=0. 8; overall survival: adjusted hazard ratio [aHR] =1. 34; P=0. 3; progression-free survival: aHR=0. 97; P=0.
9; duration of response: aHR=0. 89; P=0. 7; cumulative incidence of relapse: aHR=0. 92; P=0. 8). In summary, although axicel was associated with greater toxicity requiring more intensive management, the response rates and survival outcomes were comparable between axi-cel and liso-cel.
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