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Tisagenlecleucel 和 axicabtagene ciloleucel CAR T 细胞治疗复发或难治性弥漫性大 B 细胞淋巴瘤的真实世界比较。

A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma.

机构信息

Hematology Department, Hospices Civils de Lyon, Pierre Bénite, Lyon, France.

International Center for Infectiology Research (CIRI), Inserm U1111, Lyon, France.

出版信息

Nat Med. 2022 Oct;28(10):2145-2154. doi: 10.1038/s41591-022-01969-y. Epub 2022 Sep 22.

Abstract

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this study, we analyzed the outcome of 809 patients with R/R DLBCL after two or more previous lines of treatment who had a commercial chimeric antigen receptor (CAR) T cells order for axi-cel or tisa-cel and were registered in the retrospective French DESCAR-T registry study ( NCT04328298 ). After 1:1 propensity score matching (n = 418), the best overall response rate/complete response rate (ORR/CRR) was 80%/60% versus 66%/42% for patients treated with axi-cel compared to tisa-cel, respectively (P < 0.001 for both ORR and CRR comparisons). After a median follow-up of 11.7 months, the 1-year progression-free survival was 46.6% for axi-cel and 33.2% for tisa-cel (hazard ratio (HR) = 0.61; 95% confidence interval (CI), 0.46-0.79; P = 0.0003). Overall survival (OS) was also significantly improved after axi-cel infusion compared to after tisa-cel infusion (1-year OS 63.5% versus 48.8%; HR = 0.63; 95% CI, 0.45-0.88; P = 0.0072). Similar findings were observed using the inverse probability of treatment weighting statistical approach. Grade 1-2 cytokine release syndrome was significantly more frequent with axi-cel than with tisa-cel, but no significant difference was observed for grade ≥3. Regarding immune effector cell-associated neurotoxicity syndrome (ICANS), both grade 1-2 and grade ≥3 ICANS were significantly more frequent with axi-cel than with tisa-cel. In conclusion, our matched comparison study supports a higher efficacy and also a higher toxicity of axi-cel compared to tisa-cel in the third or more treatment line for R/R DLBCL.

摘要

阿基仑赛(axi-cel)和tisagenlecleucel(tisa-cel)在复发/难治性(R/R)弥漫性大 B 细胞淋巴瘤(DLBCL)中均显示出令人印象深刻的临床活性。在这项研究中,我们分析了在接受两线或两线以上先前治疗后,有商业嵌合抗原受体(CAR)T 细胞axi-cel 或 tisa-cel 订单,并在回顾性法国 DESCAR-T 注册研究(NCT04328298)中注册的 809 例 R/R DLBCL 患者的结局。在 1:1 倾向评分匹配(n=418)后,与 tisa-cel 相比,接受 axi-cel 治疗的患者最佳总缓解率/完全缓解率(ORR/CRR)分别为 80%/60%和 66%/42%(ORR 和 CRR 比较均 P<0.001)。在中位随访 11.7 个月后,axi-cel 的 1 年无进展生存率为 46.6%,tisa-cel 的 1 年无进展生存率为 33.2%(风险比(HR)=0.61;95%置信区间(CI),0.46-0.79;P=0.0003)。与 tisa-cel 输注相比,axi-cel 输注后总体生存(OS)也显著改善(1 年 OS 63.5%对 48.8%;HR=0.63;95%CI,0.45-0.88;P=0.0072)。使用逆概率治疗加权统计方法也观察到了类似的发现。与 tisa-cel 相比,axi-cel 显著更频繁地发生 1-2 级细胞因子释放综合征,但≥3 级无显著差异。关于免疫效应细胞相关神经毒性综合征(ICANS),axi-cel 比 tisa-cel 更频繁地发生 1-2 级和≥3 级 ICANS。总之,我们的匹配比较研究支持 axi-cel 在 R/R DLBCL 的三线或更多线治疗中比 tisa-cel 具有更高的疗效,也具有更高的毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74c9/9556323/835bd7d2f449/41591_2022_1969_Fig1_HTML.jpg

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