决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:CAR T cells vs bispecific antibody as third- or later-line large B-cell lymphoma therapy: a meta-analysis.
CAR T cells vs bispecific antibody as third- or later-line large B-cell lymphoma therapy: a meta-analysis.
CAR-T 细胞疗法在获得更高 CR 率方面优于双特异性抗体,尽管严重不良事件有所增加。
本荟萃分析评估嵌合抗原受体(CAR)T细胞疗法和双特异性抗体治疗复发/难治性弥漫性大B细胞淋巴瘤(R/R DLBCL)的疗效和安全性。我们检索MEDLINE、Embase和Cochrane数据库截至2023年7月的试验,纳入评估CAR-T及CD20×CD3双特异性抗体作为R/R DLBCL三线或后续治疗的研究。使用随机效应模型估算完全缓解(CR)率及次要结局,并通过荟萃回归调整相关协变量。共纳入16项研究、1347名患者。双抗汇总CR率为0.36(95%置信区间CI:0.29至0.43),CAR-T为0.51(95% CI:0.46至0.56;P<0.01)。仅比较双抗组中未接受过CAR-T的患者时,CAR-T优势仍存在,CR率为0.37(95% CI:0.32至0.43)。多变量荟萃回归在调整双打击淋巴瘤比例后也显示CAR-T疗效更佳。汇总1年无进展生存率结果相似(0.32比0.44;P<0.01)。3级不良事件方面,双抗相关细胞因子释放综合征、神经毒性和感染发生率分别为0.02、0.01和0.10;CAR-T分别为0.08、0.11和0.17,前两项差异显著。总之,CAR-T较双抗有更高CR率,但严重不良事件也较多。
This meta-analysis evaluates the efficacy and safety of chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). We searched MEDLINE, Embase, and Cochrane databases until July 2023 for trials assessing CAR T-cell therapies and CD20 CD3 bispecific antibodies as third or subsequent lines in R/R DLBCL. Random-effects models estimated the complete response (CR) rate and secondary outcomes, with meta-regressions adjusting for relevant covariates. Sixteen studies comprising 1347 patients were included in the pooled analysis. The pooled CR rate for bispecific antibodies was 0.36 (95% confidence interval [CI], 0.29-0.43), compared with 0.51 (95% CI, 0.46-0.56) for CAR T-cell therapy (P < .01). This superiority persisted when comparing the CAR T-cell-naive patients within the bispecific antibody group, with a CR rate of 0.37 (95% CI, 0.32-0.43). Multivariable meta-regression also revealed better efficacy of CAR T cells with adjustment for the proportion of double-hit lymphoma. The pooled 1-year progression-free survival rate mirrored these findings (0.32 [95% CI, 0.26-0.38] vs 0.44 [95% CI, 0.41-0.48]; P < .01). For adverse events of grade 3, the bispecific antibody had incidences of 0.02 (95% CI, 0.01-0.04) for cytokine release syndrome, 0.01 (95% CI, 0.00-0.01) for neurotoxicity, and 0.10 (95% CI, 0.03-0.16) for infections. The CAR T cell had rates of 0.08 (95% CI, 0.03-0.12), 0.11 (95% CI, 0.06-0.17), and 0.17 (95% CI, 0.11-0.22), respectively, with significant differences observed in the first 2 categories. In summary, CAR T-cell therapy outperformed bispecific antibody in achieving higher CR rates, although with an increase in severe adverse events.
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