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利妥昔单抗与阿基仑赛在大B细胞淋巴瘤中的真实世界比较:一项3年随访的治疗权重逆概率分析

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.

作者信息

Portuguese Andrew J, Huang Jennifer J, Jeon Yein, Taheri Mahnoosh, Albittar Aya, Liang Emily C, Hirayama Alexandre V, Kimble Erik L, Iovino Lorenzo, Poh Christina, Gopal Ajay K, Shadman Mazyar, Till Brian G, Milano Filippo, Chapuis Aude G, Otegbeye Folashade, Cassaday Ryan D, Basom Ryan S, Wu Qian Vicky, Maloney David G, Gauthier Jordan

机构信息

Fred Hutchinson Cancer Center, Seattle, WA, USA; University of Washington, Seattle, WA.

Washington State University, Pullman, WA.

出版信息

Haematologica. 2025 Sep 1;110(9):2040-2054. doi: 10.3324/haematol.2024.287010. Epub 2025 Mar 13.

Abstract

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.

摘要

利妥昔单抗(liso-cel)和阿基仑赛(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用于复发/难治性大B细胞淋巴瘤(LBCL)的嵌合抗原受体(CAR)T细胞疗法。然而,缺乏对其疗效和毒性进行长期随访的比较性真实世界分析。我们对弗雷德·哈钦森癌症中心按照标准治疗方案接受商业利妥昔单抗或阿基仑赛治疗的160例LBCL患者进行了一项回顾性研究。使用治疗权重的逆概率(IPTW)来减轻治疗分配偏倚,并进行多变量调整以尽量减少其他混杂因素,我们评估了CAR T细胞产品类型对结局的影响。阿基仑赛与显著更高的细胞因子释放综合征(CRS;1级及以上:调整优势比[aOR]=4.27;P=0.004;2级及以上:aOR=2.88;P=0.006)、免疫效应细胞相关神经毒性综合征(ICANS;1级及以上:aOR=2.10;P=0.048)以及免疫效应细胞相关血液毒性(ICAHT;1级及以上:aOR=8.09;P<0.001;2级及以上:aOR=3.86;P=0.001)发生率相关。阿基仑赛还与更频繁使用支持性护理措施相关,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)。我们无法证实利妥昔单抗与阿基仑赛在缓解率和生存结局方面存在统计学显著差异(完全缓解:aOR=1.12;P=0.8;总生存:调整风险比[aHR]=1.34;P=0.3;无进展生存:aHR=0.97;P=0.9;缓解持续时间:aHR=0.89;P=0.7;复发累积发生率:aHR=0.92;P=0.8)。总之,尽管阿基仑赛与需要更强化管理的更大毒性相关,但阿基仑赛和利妥昔单抗在缓解率和生存结局方面具有可比性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be3/12399936/14d42b6b7433/1102040.fig1.jpg

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