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:Real-World Experience of Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed or Refractory Aggressive B-cell Lymphomas: A Single-Institution Experience.
Real-World Experience of Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed or Refractory Aggressive B-cell Lymphomas: A Single-Institution Experience.
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我们单中心的真实世界 R/R aBCL 患者队列显示出与 ZUMA-1 和 JULIET 试验及已发表真实世界研究相似的疗效结果。
靶向CD19的嵌合抗原受体(CAR)T细胞疗法革新了复发/难治性(R/R)侵袭性B细胞淋巴瘤(aBCL)患者的治疗。里程碑式ZUMA-1和JULIET试验的结果已在多家机构的真实世界环境中得到重复验证;与非双重/三重打击淋巴瘤患者相比,双重打击(DHL)或三重打击(THL)患者也显示出不劣的结局。
这项回顾性队列研究纳入2017年10月至2020年6月在加州大学洛杉矶分校接受CAR-T 治疗的53例R/R aBCL患者。采用描述性统计汇总患者特征、淋巴瘤相关变量和关注的结局,并用Fisher精确检验比较各组。采用Kaplan-Meier法分析总生存期(OS)、无进展生存期(PFS)和缓解持续时间(DOR)。通过单变量和多变量Cox回归分析评估显著预后变量。
中位随访15.2个月时,该队列的总缓解率和完全缓解率分别为72%和64%(n=34)。中位DOR、PFS和OS分别尚未达到、7.9个月和17.7个月。单变量分析显示,DHL/THL状态是唯一与CAR-T 治疗后复发显著相关的临床特征(OR 5.9,P=0.015)。
本单中心R/R aBCL真实世界队列的疗效结局与ZUMA-1、JULIET试验及已发表的真实世界研究相似。研究结果提示,DHL/THL患者可能受益于新型CAR-T 构建体、免疫调节药物维持策略或异基因造血细胞移植(HCT)。
CD19-directed chimeric antigen T-cell receptor (CAR-T) therapies have revolutionized the treatment of patients with relapsed/refractory (R/R) aggressive B-cell lymphomas (aBCL). The results of the landmark ZUMA-1 and JULIET trials have been reproducible in real-world settings across multiple institutions, and patients with double (DHL) or triple (THL) hit lymphomas have demonstrated non-inferior outcomes compared to non-DHL/THL counterparts.
This retrospective cohort study included 53 patients with R/R aBCL who received CAR-T from October 2017 to June 2020 at the University of California, Los Angeles. Patient characteristics, lymphoma-related variables and outcomes of interest were summarized using descriptive statistics and compared between groups by Fisher's exact test. Kaplan-Meier methods were used for analysis of OS, progression free survival (PFS), and duration of response (DOR). Univariate and multivariate cox regression analysis were performed to evaluate for significant prognostic variables.
With a median follow-up of 15.2 months, this cohort demonstrated overall response rate and complete response rate of 72% and 64% (n = 34), respectively. The median DOR, PFS and OS were not reached, 7.9 and 17.7 months, respectively. By univariate analysis, DHL/THL status was the only clinical feature significantly associated with relapse post-CAR-T (OR 5.9, P = .015).
Our single-institution, real-world cohort of R/R aBCL patients demonstrated similar efficacy outcomes to those of the ZUMA-1 and JULIET trials and published real-world studies. Our findings suggest DHL/THL patients may benefit from novel CAR-T constructs, maintenance strategies with immunomodulatory agents or allogeneic-HCT.
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