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:Efficacy of Salvage Treatments in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Including Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review and Meta-Analysis.
Efficacy of Salvage Treatments in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Including Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review and Meta-Analysis.
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尽管若干方案被粗略地分组归类,但 CAR-T 细胞治疗在二线治疗中并未优于化疗后 ASCT,在不符合 ASCT 条件时也并未优于几种近期开发的药物。
我们拟通过荟萃分析评估复发/难治性弥漫大B细胞淋巴瘤(R/R DLBCL)的挽救治疗疗效。
根据患者是否符合自体干细胞移植(ASCT)条件,将R/R DLBCL试验分为两组,并分别开展荟萃分析。采用随机效应模型估算1年无进展生存期(PFS)率,并以嵌合抗原受体(CAR)T细胞疗法作为参照治疗。
汇总分析纳入17项研究中的26个符合ASCT条件队列,共2,924例患者;以及53项研究中的59个不符合ASCT条件队列,共3,617例患者。在符合ASCT条件组中,CAR-T 组汇总1年PFS率为0.40(95%置信区间[CI]0.15–0.65),化疗后计划ASCT组为0.34(95% CI 0.30–0.37)。荟萃回归分析显示两种治疗无显著差异。在不符合ASCT条件组中,CAR-T 组汇总1年PFS为0.40(95% CI 0.35–0.46),tafasitamab组主要结局数值最高,为0.47(95% CI 0.37–0.57)。CAR-T 疗效显著优于化疗以及基于ibrutinib、lenalidomide和selinexor的治疗。但在校正既往治疗线数中位数后,loncastuximab、polatuzumab联合bendamustine和rituximab,以及tafasitamab组与CAR-T 疗法疗效相当。
虽然分析中的若干方案为便于分类而进行了较粗略的归组,CAR-T 疗法在二线治疗中并未优于化疗后ASCT;对于不符合ASCT条件的患者,也未优于若干近期开发的药物。
We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis.
R/R DLBCL trials were divided into two groups based on eligibility for autologous stem-cell transplantation (ASCT), and meta-analysis of each group was performed. Random effects models were used to estimate the 1-year progression-free survival (PFS) rate, and chimeric antigen receptor (CAR) T-cell therapy was used as reference treatment.
Twenty-six ASCT-eligible cohorts from 17 studies comprising 2,924 patients and 59 ASCT-ineligible cohorts from 53 studies comprising 3,617 patients were included in the pooled analysis. In the ASCT-eligible group, the pooled 1-year PFS rate was 0.40 (95% confidence interval [CI], 0.15 to 0.65) for the CAR T-cell group and 0.34 (95% CI, 0.30 to 0.37) for the group with chemotherapy followed by ASCT intention. The two treatments were not significantly different in meta-regression analysis. In the ASCT-ineligible group, the pooled 1-year PFS was 0.40 (95% CI, 0.35 to 0.46) for CAR T-cell, and the highest primary outcome was 0.47 (95% CI, 0.37 to 0.57) for the tafasitamab group. CAR T-cell therapy showed significantly better outcomes than chemotherapy and therapies based on ibrutinib, lenalidomide, and selinexor. However, loncastuximab, polatuzumab plus bendamustine and rituximab, and the tafasitamab group showed no different efficacy than CAR T-cell therapy after adjusting for median number of previous lines of treatment.
Although several regimens were crudely grouped for classification, CAR T-cell therapy did not outperform chemotherapy followed by ASCT in the second-line setting or several recently developed agents in the ASCT-ineligible setting.
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