Dana-Farber Cancer Institute, Boston, Massachusetts.
H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.
Transplant Cell Ther. 2022 Sep;28(9):581.e1-581.e8. doi: 10.1016/j.jtct.2022.05.026. Epub 2022 May 21.
Axicabtagene ciloleucel (axi-cel) is a standard-of-care for patients with relapsed or refractory (r/r) large B cell lymphoma who have received 2 or more lines of prior therapy. Patients receiving axi-cel in the real world could have broader a demographic, disease, and treatment profile compared with that of the cohort in the pivotal ZUMA-1 trial. The present study was conducted to evaluate the outcomes of axi-cel therapy in the real-world setting. A total of 1297 patients receiving commercial axi-cel between 2017 and 2020 were selected from the Center for International Blood and Marrow Transplant Research's data registry, of whom 739 (57%) would have been ineligible for inclusion in the ZUMA-1 cohort. Efficacy and safety outcomes were described for the entire cohort and by ZUMA-1 eligibility. Their associations with age, Eastern Cooperative Oncology Group Performance Score, and comorbidities were evaluated using multivariable logistic and Cox regressions. At a median follow-up of 12.9 months, the overall response rate (ORR) was 73%, with a 56% complete response (CR) rate. Median overall survival (OS) and progression-free survival (PFS) were 21.8 months (95% confidence interval [CI], 17.4 to 28.8 months) and 8.6 months (95% CI, 6.5 to 12.1 months), respectively. Duration of response (DOR) was comparable in the ZUMA-1 ineligible patients and ZUMA-1 eligible patients (62% by 1 year [95% CI, 57% to 66%] versus 67% [95% CI, 62% to 72%]). Patients age ≥65 years had favorable ORR (odds ratio [OR], 1.39; 95% CI, 1.05 to 1.83) despite having a higher risk of cytokine release syndrome (CRS) (OR, 1.41; 95% CI, 1.02 to 1.94) and immune effector cell-associated neurotoxicity syndrome (ICANS) (OR, 1.77; 95% CI, 1.39-2.26). Eastern Cooperative Oncology Group Performance Score ≥2 was associated with inferior efficacy outcomes (OR for ORR, 0.32; 95% CI, 0.18-0.56; hazard ratio [HR] for OS, 3.27; 95% CI, 2.37 to 4.52) and higher incidence of ICANS (OR, 2.63; 95% CI, 1.40 to 4.93). The patients ineligible for ZUMA-1 still had a durable response with axi-cel. Elderly patients had favorable efficacy outcomes despite higher rates of CRS and ICANS. Patient selection for standard-of-care axi-cel should consider comorbidities and risk-to-benefit ratio rather than be based strictly on ZUMA-1 eligibility.
阿基仑赛（axi-cel）是一种标准的治疗方法，适用于接受过 2 线或以上先前治疗的复发或难治性（r/r）大 B 细胞淋巴瘤患者。与关键的 ZUMA-1 试验队列相比，在现实世界中接受 axi-cel 的患者可能具有更广泛的人口统计学、疾病和治疗特征。本研究旨在评估 axi-cel 治疗在现实环境中的结果。从国际血液和骨髓移植研究中心的数据登记处选择了 2017 年至 2020 年间接受商业 axi-cel 的 1297 名患者，其中 739 名（57%）不符合 ZUMA-1 队列的入选标准。描述了整个队列和符合 ZUMA-1 标准的患者的疗效和安全性结果。使用多变量逻辑和 Cox 回归评估了它们与年龄、东部合作肿瘤学组表现评分和合并症的关系。在中位随访 12.9 个月时，总缓解率（ORR）为 73%，完全缓解（CR）率为 56%。中位总生存期（OS）和无进展生存期（PFS）分别为 21.8 个月（95%置信区间[CI]，17.4 至 28.8 个月）和 8.6 个月（95%CI，6.5 至 12.1 个月）。在不符合 ZUMA-1 标准的患者和符合 ZUMA-1 标准的患者中，缓解持续时间（DOR）相当（1 年时为 62%[95%CI，57%至 66%]与 67%[95%CI，62%至 72%]）。年龄≥65 岁的患者尽管发生细胞因子释放综合征（CRS）（OR，1.41；95%CI，1.02 至 1.94）和免疫效应细胞相关神经毒性综合征（ICANS）（OR，1.77；95%CI，1.39 至 2.26）的风险较高，但具有良好的 ORR（优势比[OR]，1.39；95%CI，1.05 至 1.83）。东部合作肿瘤学组表现评分≥2 与疗效结果较差相关（OR 为 ORR，0.32；95%CI，0.18 至 0.56；OS 的 HR，3.27；95%CI，2.37 至 4.52）和更高的 ICANS 发生率（OR，2.63；95%CI，1.40 至 4.93）。不符合 ZUMA-1 标准的患者仍能从 axi-cel 中获得持久的缓解。尽管 CRS 和 ICANS 的发生率较高，但老年患者的疗效较好。选择 axi-cel 作为标准治疗应考虑合并症和风险效益比，而不是严格基于 ZUMA-1 的资格。
