Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Memorial Sloan-Kettering Cancer Center, New York, NY.
Blood. 2022 Aug 25;140(8):851-860. doi: 10.1182/blood.2021014375.
In the pivotal ZUMA-5 trial, axicabtagene ciloleucel (axi-cel; an autologous anti-CD19 chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients. Here, outcomes from ZUMA-5 are compared with the international SCHOLAR-5 cohort, which applied key ZUMA-5 trial eligibility criteria simulating randomized controlled trial conditions. SCHOLAR-5 data were extracted from institutions in 5 countries, and from 1 historical clinical trial, for r/r FL patients who initiated a third or higher line of therapy after July 2014. Patient characteristics were balanced through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. Time-to-event outcomes were evaluated using weighted Kaplan-Meier analysis. Overall response rate (ORR) and complete response (CR) rate were compared using weighted odds ratios. The 143 ScHOLAR-5 patients reduced to an effective sample of 85 patients after SMR weighting vs 86 patients in ZUMA-5. Median follow-up time was 25.4 and 23.3 months for SCHOLAR-5 and ZUMA-5. Median overall survival (OS) and progression-free survival (PFS) in SCHOLAR-5 were 59.8 months and 12.7 months and not reached in ZUMA-5. Hazard ratios for OS and PFS were 0.42 (95% confidence interval [CI], 0.21-0.83) and 0.30 (95% CI, 0.18-0.49). The ORR and CR rate were 49.9% and 29.9% in SCHOLAR-5 and 94.2% and 79.1% in ZUMA-5, for odds ratios of 16.2 (95% CI, 5.6-46.9) and 8.9 (95% CI, 4.3-18.3). Compared with available therapies, axi-cel demonstrated an improvement in meaningful clinical endpoints, suggesting axi-cel addresses an important unmet need for r/r FL patients. This trial was registered at www.clinicaltrials.gov as #NCT03105336.
在关键的 ZUMA-5 试验中，axi-cel（一种自体抗 CD19 嵌合抗原受体 T 细胞疗法）在复发/难治性（r/r）滤泡淋巴瘤（FL）患者中显示出高比例的持久缓解率。在这里，ZUMA-5 的结果与国际 SCHOLAR-5 队列进行了比较，该队列应用了关键的 ZUMA-5 试验纳入标准，模拟了随机对照试验的条件。SCHOLAR-5 数据来自 5 个国家的机构，以及 1 项历史临床试验，涉及 2014 年 7 月后接受第 3 次或更高线治疗的 r/r FL 患者。通过使用标准化死亡率比（SMR）加权对预设预后因素进行倾向评分，平衡患者特征。使用加权 Kaplan-Meier 分析评估生存时间。使用加权优势比比较总缓解率（ORR）和完全缓解（CR）率。经过 SMR 加权后，143 名 ScHOLAR-5 患者减少到 85 名有效样本，而 ZUMA-5 中为 86 名。SCHOLAR-5 和 ZUMA-5 的中位随访时间分别为 25.4 个月和 23.3 个月。SCHOLAR-5 的中位总生存期（OS）和无进展生存期（PFS）分别为 59.8 个月和 12.7 个月，ZUMA-5 未达到。OS 和 PFS 的风险比分别为 0.42（95%CI，0.21-0.83）和 0.30（95%CI，0.18-0.49）。SCHOLAR-5 的 ORR 和 CR 率分别为 49.9%和 29.9%，ZUMA-5 分别为 94.2%和 79.1%，优势比为 16.2（95%CI，5.6-46.9）和 8.9（95%CI，4.3-18.3）。与现有疗法相比，axi-cel 在有意义的临床终点方面显示出改善，表明 axi-cel 满足了 r/r FL 患者的重要未满足需求。该试验在 www.clinicaltrials.gov 上注册为 #NCT03105336。
