The University of Texas MD Anderson Cancer Center, Houston, TX.
Moffitt Cancer Center, Tampa, FL.
J Clin Oncol. 2020 Sep 20;38(27):3119-3128. doi: 10.1200/JCO.19.02104. Epub 2020 May 13.
Axicabtagene ciloleucel (axi-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory large B-cell lymphoma (LBCL) on the basis of the single-arm phase II ZUMA-1 trial, which showed best overall and complete response rates in infused patients of 83% and 58%, respectively. We report clinical outcomes with axi-cel in the standard-of-care (SOC) setting for the approved indication.
Data were collected retrospectively from all patients with relapsed/refractory LBCL who underwent leukapheresis as of September 30, 2018, at 17 US institutions with the intent to receive SOC axi-cel. Toxicities were graded and managed according to each institution's guidelines. Responses were assessed as per Lugano 2014 classification.
Of 298 patients who underwent leukapheresis, 275 (92%) received axi-cel therapy. Compared with the registrational ZUMA-1 trial, 129 patients (43%) in this SOC study would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis. Among the axi-cel-treated patients, grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 7% and 31%, respectively. Nonrelapse mortality was 4.4%. Best overall and complete response rates in infused patients were 82% (95% CI, 77% to 86%) and 64% (95% CI, 58% to 69%), respectively. At a median follow-up of 12.9 months from the time of CAR T-cell infusion, median progression-free survival was 8.3 months (95% CI, 6.0 to15.1 months), and median overall survival was not reached. Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 and elevated lactate dehydrogenase had shorter progression-free and overall survival on univariable and multivariable analysis.
The safety and efficacy of axi-cel in the SOC setting in patients with relapsed/refractory LBCL was comparable to the registrational ZUMA-1 trial.
基于单臂二期 ZUMA-1 试验，阿基仑赛（axi-cel）获批用于治疗复发/难治性大 B 细胞淋巴瘤（LBCL），该试验中入组患者的总缓解率和完全缓解率分别为 83%和 58%。我们报告了 axi-cel 在获批适应证的标准治疗（SOC）环境中的临床结果。
自 2018 年 9 月 30 日起，17 家美国机构回顾性收集了所有接受白细胞分离术的复发/难治性 LBCL 患者的数据，其目的是接受 SOC axi-cel 治疗。毒性根据每个机构的指南进行分级和管理。根据 Lugano 2014 分类评估反应。
在 298 名接受白细胞分离术的患者中，275 名（92%）接受了 axi-cel 治疗。与注册的 ZUMA-1 试验相比，在这项 SOC 研究中，有 129 名患者（43%）由于白细胞分离术时的合并症而不符合 ZUMA-1 的入组标准。在接受 axi-cel 治疗的患者中，分别有 7%和 31%发生了≥3 级细胞因子释放综合征和神经毒性。非复发死亡率为 4.4%。入组患者的总缓解率和完全缓解率分别为 82%（95%CI，77%至 86%）和 64%（95%CI，58%至 69%）。从 CAR T 细胞输注到中位随访 12.9 个月，中位无进展生存期为 8.3 个月（95%CI，6.0 至 15.1 个月），中位总生存期未达到。Eastern Cooperative Oncology Group 表现状态为 2-4 分和乳酸脱氢酶升高的患者在单变量和多变量分析中均显示无进展生存期和总生存期较短。
在复发/难治性 LBCL 患者的 SOC 环境中，axi-cel 的安全性和疗效与注册的 ZUMA-1 试验相当。
