肿瘤细胞治疗研究
英文原题：Five-year follow-up of patients with relapsed/refractory mantle cell lymphoma treated with anti-CD19 CAR T-cell therapy in ZUMA-2, Cohorts 1 and 2.
ZUMA-2 患者在接受 5 年随访后仍持续获得持久缓解，且长期安全性可预测，支持继续在 R/R MCL 中使用 brexu-cel。由于患者数量少且基线特征不匹配，无法对 axi-cel 治疗患者和队列 2 的结局进行解读。
接受brexucabtagene autoleucel（brexu-cel）——一种自体抗CD19嵌合抗原受体（CAR）T细胞疗法——治疗在关键性ZUMA-2队列1研究中治疗的60例复发/难治性套细胞淋巴瘤（R/R MCL）患者中显示出较高的客观缓解率（93%）和完全缓解率（67%）。随后，brexu-cel在美国和欧盟获批用于治疗成人R/R MCL（在欧盟为既往接受过2种治疗后）。在此，我们报告关键性ZUMA-2队列1研究（N = 68）的5年结局，以及两个先前未发表的ZUMA-2数据集：队列1中10例接受axi-cel治疗的患者和队列2中14例接受较低剂量brexu-cel治疗患者的长期结局。
ZUMA-2所有队列的主要终点为客观缓解率。关键次要终点包括缓解持续时间（DOR）、总生存期（OS）和安全性。患者可在24个月后转入一项长期随访研究，以监测生存情况和可能与brexu-cel相关的特定不良事件。队列1中的患者接受单次输注2×10^6 抗CD19 CAR T细胞/kg（axi-cel或brexu-cel）。队列2中的患者接受0.5×10^6 抗CD19 CAR T细胞/kg（brexu-cel）。
关键队列（N = 68）的中位随访时间为 67.8 个月（范围，58.2-88.6），根据研究者评估，中位 DOR 为 36.5 个月（n = 60）。中位 OS 为 46.5 个月（95% CI，24.5-60.2；N = 68），在完全缓解患者中为 60.2 个月（95% CI，42.8-不可估计）（n = 46）。在缓解者中，累积复发相关死亡和非复发相关死亡的 5 年发生率分别为 40%（24/60）和 22%（13/60）。本文报告了接受 axi-cel 治疗患者（N = 10）和队列 2（N = 14）的描述性结局。任何患者均未报告 5 级细胞因子释放综合征或神经系统事件、后续 T 细胞恶性肿瘤或新的安全性信号。
BACKGROUND: Treatment with brexucabtagene autoleucel (brexu-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated a high objective response rate (93%) and complete response rate (67%) in 60 patients with relapsed/refractory mantle cell lymphoma (R/R MCL) treated in the pivotal ZUMA-2 Cohort 1 study. Subsequently, brexu-cel was approved in the United States and European Union for the treatment of adults with R/R MCL (after 2 prior therapies in the European Union). Here we report 5-year outcomes from the pivotal ZUMA-2 Cohort 1 study (N = 68), as well as two previously unpublished ZUMA-2 data sets, long-term outcomes in 10 patients who received axi-cel in Cohort 1 and in 14 patients who received a lower dose of brexu-cel in Cohort 2. METHODS: The primary endpoint for all cohorts of ZUMA-2 was objective response rate. Key secondary endpoints included duration of response (DOR), overall survival (OS), and safety. Patients could transition to a long-term follow-up study after 24 months for monitoring of survival and select adverse events possibly related to brexu-cel. Patients in Cohort 1 received a single infusion of 2 10 6 anti-CD19 CAR T cells/kg (axi-cel or brexu-cel). Patients in Cohort 2 received 0.5 10 6 anti-CD19 CAR T cells/kg (brexu-cel). RESULTS: Median follow-up for the pivotal cohort (N = 68) was 67.8 months (range, 58.2-88.6) with a median DOR of 36.5 months (n = 60), per investigator review. Median OS was 46.5 months (95% CI, 24.5-60.2; N = 68) and was 60.2 months (95% CI, 42.8-not estimable) in patients with complete response (n = 46). The 5-year incidence of cumulative relapse-related and non-relapse-related mortality was 40% (24/60) and 22% (13/60) in responders, respectively. Descriptive outcomes for axi-cel-treated patients (N = 10) and Cohort 2 (N = 14) are reported herein. No Grade 5 cytokine-release syndrome or neurologic events, subsequent T-cell malignancies, or new safety signals were reported in any patient. CONCLUSIONS: Patients in ZUMA-2 continued to have durable responses after 5 years of follow-up with predictable long-term safety, supporting the continued use of brexu-cel in R/R MCL. Interpretations of outcomes in axi-cel-treated patients and Cohort 2 are not feasible due to small patient numbers and unmatched baseline characteristics. TRIAL REGISTRATION: NCT02601313 and NCT05041309.
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