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商业性抗 CD19 CAR T 细胞疗法治疗欧洲中心复发/难治性侵袭性 B 细胞淋巴瘤患者。

Commercial anti-CD19 CAR T cell therapy for patients with relapsed/refractory aggressive B cell lymphoma in a European center.

机构信息

Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France.

Claude Bernard Lyon 1 University, Lyon, France.

出版信息

Am J Hematol. 2020 Nov;95(11):1324-1333. doi: 10.1002/ajh.25951. Epub 2020 Aug 25.


DOI:10.1002/ajh.25951
PMID:32744738
Abstract

Two autologous anti-CD19 chimeric antigen receptors (CAR) T cells (axicabtagene ciloleucel [axi-cel] and tisagenlecleucel [tisa-cel]) are commercially approved in Europe for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). We performed a retrospective study to evaluate patterns of use, efficacy and safety for axi-cel and tisa-cel. Data from 70 patients who underwent apheresis for commercial CAR T cells between January 2018 and November 2019 in our institution were retrospectively collected. Sixty-one patients were infused. The median age at infusion was 59 years old (range 27-75 years). The median number of prior therapies was 3 (range, 2-6). The overall response rates (ORRs) at 1 month and 3 months were 63% and 45%, respectively, with 48% and 39% achieving a complete response (CR), respectively. After a median follow-up after infusion of 5.7 months, the median progression-free survival (PFS) was 3.0 months (95% CI, 2.8-8.8 months), and the median overall survival (OS) was 11.8 months (95% CI, 6.0-12.6 months). In multivariate analysis, factors associated with poor PFS were the number of previous lines of treatment before CAR T cells (≥4) (P = .010) and a C reactive protein (CRP) value >30 mg/L at the time of lymphodepletion (P < .001). Likewise, the only factor associated with a shorter OS was CRP >30 mg/L (P = .009). Cytokine release syndrome (CRS) of any grade occurred in 85% of patients, including 8% of patients with CRS of grade 3 or higher. Immune cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 28% of patients, including 10% of patients with ICANS of grade 3 or higher. Regarding efficacy and safety, no significant difference was found between axi-cel and tisa-cel. This analysis describes one of the largest real-life cohorts of patients treated with axi-cel and tisa-cel for R/R aggressive B cell lymphoma in Europe.

摘要

两种自体抗 CD19 嵌合抗原受体(CAR)T 细胞(axicabtagene ciloleucel [axi-cel] 和 tisagenlecleucel [tisa-cel])在欧洲被商业化批准用于治疗复发/难治性(R/R)弥漫性大 B 细胞淋巴瘤(DLBCL)。我们进行了一项回顾性研究,以评估 axi-cel 和 tisa-cel 的使用模式、疗效和安全性。我们回顾性地收集了 2018 年 1 月至 2019 年 11 月期间在我院接受商业 CAR T 细胞治疗的 70 名患者的单采术数据。61 名患者接受了输注。输注时的中位年龄为 59 岁(范围 27-75 岁)。中位既往治疗数为 3(范围 2-6)。1 个月和 3 个月的总缓解率(ORR)分别为 63%和 45%,分别有 48%和 39%达到完全缓解(CR)。在输注后中位随访 5.7 个月时,中位无进展生存期(PFS)为 3.0 个月(95%CI,2.8-8.8 个月),中位总生存期(OS)为 11.8 个月(95%CI,6.0-12.6 个月)。在多变量分析中,与较差的 PFS 相关的因素包括 CAR T 细胞前的治疗线数(≥4)(P=0.010)和淋巴细胞耗竭时 C 反应蛋白(CRP)值>30mg/L(P<0.001)。同样,唯一与较短 OS 相关的因素是 CRP>30mg/L(P=0.009)。任何等级的细胞因子释放综合征(CRS)发生在 85%的患者中,包括 8%的患者发生 3 级或更高等级的 CRS。任何等级的免疫细胞相关神经毒性综合征(ICANS)发生在 28%的患者中,包括 10%的患者发生 3 级或更高等级的 ICANS。关于疗效和安全性,axi-cel 和 tisa-cel 之间没有发现显著差异。这项分析描述了在欧洲接受 axi-cel 和 tisa-cel 治疗 R/R 侵袭性 B 细胞淋巴瘤的患者中最大的真实队列之一。

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