在ZUMA-1的第二阶段中，进行了单臂、多中心、登记试验，使用axicabtagene ciloleucel (axi-cel)自体抗CD19嵌合抗原受体(CAR)T细胞疗法，对难治性大B细胞淋巴瘤（LBCL）患者在2年内表现出持久的反应。在此，我们旨在评估随访5年后ZUMA-1的生存和安全性。符合条件的成年难治性LBCL（弥漫性大B细胞淋巴瘤、原发性纵隔B细胞淋巴瘤和转化的滤泡性淋巴瘤）患者接受淋巴清除化疗后，接受axi-cel输注，目标是每公斤2×106细胞。研究员评估响应、更新的生存、安全性和药物动力学结果。在101例接受治疗的患者中，客观响应率为83%(完全缓解率为58%)，中位随访63.1个月时，在31%的患者中反应仍在持续。总体生存中位数为25.8个月，估计的5年总生存率为42.6%。在不考虑与疾病进展无关的死亡的情况下，预计5年疾病特异性生存率为51.0%。此后的跟踪未观察到新的严重不良事件或与axi-cel相关的死亡情况。在3年内，所有可评估的患者周围血液B细胞都可检测到，91%的患者具有多克隆B细胞恢复。持续的60个月反应与早期CAR T细胞扩张有关。总之，这项ZUMA-1的5年随访分析显示，在难治性LBCL患者中，总体生存和疾病特异性生存持久，没有发现新的安全信号。对于持久响应并非需要长时间的B细胞无效。这些发现支持axi-cel在侵袭性B细胞淋巴瘤的患者亚组中的治愈潜力。ClinicalTrials.gov，编号为NCT02348216。Copyright © 2023美国血液学会。

In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we aimed to assess survival and safety in ZUMA-1 after 5 years of follow-up. Eligible adults with refractory LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma) received lymphodepleting chemotherapy followed by axi-cel infusion targeted at 2×106 cells/kg. Investigator-assessed response, updated survival, safety, and pharmacokinetic outcomes were assessed in treated patients. The objective response rate in the 101 treated patients was 83% (58% complete response rate), and with a median follow-up of 63.1 months, responses were ongoing at data cutoff in 31%. Median overall survival (OS) was 25.8 months and the estimated 5-year OS rate was 42.6%. Disease-specific survival (excluding deaths unrelated to disease progression) estimated at 5 years was 51.0%. No new serious adverse events or deaths related to axi-cel were observed after additional follow-up. Peripheral blood B cells were detectable in all evaluable patients at 3 years with polyclonal B-cell recovery in 91%. Ongoing responses at 60 months were associated with early CAR T-cell expansion. In conclusion, this 5-year follow-up analysis of ZUMA-1 demonstrates sustained overall and disease-specific survival, with no new safety signals in patients with refractory LBCL. Protracted B-cell aplasia was not required for durable responses. These findings support the curative potential of axi-cel in a subset of patients with aggressive B-cell lymphomas. ClinicalTrials.gov, number NCT02348216.Copyright © 2023 American Society of Hematology.