UCLA Medical Center, Hematology Oncology, Los Angeles CA.
UCLA Medical Center, Internal Medicine, Los Angeles CA.
Clin Lymphoma Myeloma Leuk. 2021 Dec;21(12):861-872. doi: 10.1016/j.clml.2021.07.002. Epub 2021 Jul 19.
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.
CD19 导向的嵌合抗原受体(CAR-T)疗法彻底改变了复发/难治性(R/R)侵袭性 B 细胞淋巴瘤(aBCL)患者的治疗方法。ZUMA-1 和 JULIET 试验的结果在多个机构的真实环境中得到了重现,并且双打击(DHL)或三打击(THL)淋巴瘤患者的结果与非 DHL/THL 患者相比并不劣。
这项回顾性队列研究纳入了 2017 年 10 月至 2020 年 6 月期间在加利福尼亚大学洛杉矶分校接受 CAR-T 治疗的 53 例 R/R aBCL 患者。使用描述性统计方法总结患者特征、淋巴瘤相关变量和感兴趣的结局,并通过 Fisher 确切检验比较组间差异。使用 Kaplan-Meier 方法分析总生存期(OS)、无进展生存期(PFS)和缓解持续时间(DOR)。进行单变量和多变量 Cox 回归分析以评估显著的预后变量。
中位随访时间为 15.2 个月,该队列的总缓解率和完全缓解率分别为 72%(n=34)和 64%(n=34)。中位 DOR、PFS 和 OS 均未达到,分别为 7.9、17.7 个月。单变量分析显示,DHL/THL 状态是唯一与 CAR-T 后复发显著相关的临床特征(OR 5.9,P=.015)。
我们的单机构真实世界 R/R aBCL 患者队列的疗效结果与 ZUMA-1 和 JULIET 试验以及已发表的真实世界研究相似。我们的研究结果表明,DHL/THL 患者可能受益于新型 CAR-T 构建体、免疫调节剂维持策略或同种异体-HCT。