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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome (a DESCAR-T study).
Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome (a DESCAR-T study).
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靶向CD19的嵌合抗原受体(CAR)T细胞已被批准用于治疗复发/难治性大B细胞淋巴瘤。血液毒性是最常见的CAR-T 细胞相关不良事件。输血支持是严重血细胞减少的替代标志物。输血影响患者的生活质量,具有特定的毒性,并且已知会通过所谓的输血相关免疫调节影响免疫力,从而可能影响CAR-T 细胞的疗效。
我们分析了来自法国DESCAR-T 注册中心的671例患者的数据,这些患者具有完整的输血数据。总体而言,分别有401例(59.8%)和378例(56.3%)患者在CAR-T 细胞输注前和输注后6个月期间接受了输血。接受输血的患者数量和平均输血制品数量在CAR-T 细胞输注前6个月期间增加,在输注后第一个月(早期阶段)达到峰值,随后随时间推移而减少。早期阶段输血的预测因素为年龄>60岁、ECOG PS 2、接受axicabtagene ciloleucel治疗、CAR-T 细胞输注前输血以及CAR-HEMATOTOX评分2。晚期输血(输注后1至6个月之间)的预测因素为CAR-T 细胞输注前输血、CAR-HEMATOTOX评分2、ICANS 3(针对红细胞[RBC]输血)以及tocilizumab使用(针对血小板输血)。早期输血和晚期血小板(而非RBC)输血与较短的无进展生存期和总生存期相关。输血人群的淋巴瘤相关死亡率和非复发死亡率均增加。
我们的数据揭示了早期和晚期血细胞减少的机制,以及输血对CAR-T 细胞疗效和毒性的潜在影响。
Chimeric antigen receptor (CAR) T-cells targeting CD19 have been approved for the treatment of relapse/refractory large B-cell lymphoma. Hematotoxicity is the most frequent CAR T-cell-related adverse event. Transfusion support is a surrogate marker of severe cytopenias. Transfusion affects patients' quality of life, presents specific toxicities, and is known to affect immunity through the so-called transfusion-related immunomodulation that may affect CAR T-cell efficacy.
We analyzed data from 671 patients from the French DESCAR-T registry for whom exhaustive transfusion data were available.
Overall, 401 (59. 8%) and 378 (56. 3%) patients received transfusion in the 6-month period before and after CAR T-cell infusion, respectively. The number of patients receiving transfusion and the mean number of transfused products increased during the 6-month period before CAR T-cell infusion, peaked during the first month after infusion (early phase), and decreased over time. Predictive factors for transfusion at the early phase were age >60 years, ECOG PS 2, treatment with axicabtagene ciloleucel, pre-CAR T-cell transfusions, and CAR-HEMATOTOX score 2.
Predictive factors for late transfusion (between 1 and 6 months after infusion) were pre-CAR T-cell transfusions, CAR-HEMATOTOX score 2, ICANS 3 (for red blood cells [RBC] transfusion), and tocilizumab use (for platelets transfusion). Early transfusions and late platelets (but not RBC) transfusions were associated with a shorter progression-free survival and overall survival. Lymphoma-related mortality and nonrelapse mortality were both increased in the transfused population.
Our data shed light on the mechanisms of early and late cytopenia and on the potential impact of transfusions on CAR T-cell efficacy and toxicity.
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