Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
Precision HEOR, Oakland, California.
Biol Blood Marrow Transplant. 2020 Sep;26(9):1581-1588. doi: 10.1016/j.bbmt.2020.06.008. Epub 2020 Jun 17.
Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are autologous anti-CD19 chimeric antigen receptor T (CAR T) cell therapies for the treatment of patients with relapsed/refractory large B cell lymphoma (RR-LBCL). Both can induce durable responses; however, cross-trial comparisons are difficult due to differences in study design. In this study, the registration trials of axi-cel and tisa-cel were compared using a matching adjusted indirect comparison (MAIC). A MAIC was performed to adjust for differences in patient characteristics between trials. The estimates for the ZUMA-1 (axi-cel) trial were adjusted using patient-level data to match the study population in JULIET (tisa-cel) for key variables: International Prognostic Index), Eastern Cooperative Oncology Group score, stage, refractoriness or relapsed disease, double/triple hit status, cell of origin, and number of prior lines of therapy. The endpoints analyzed were response, overall survival (OS), and adverse events. After adjusting for differences in patient characteristics between trials, axi-cel was associated with a greater objective response rate (relative risk [RR]=1.61; 95% confidence interval [CI], 1.29 to 2.01) and complete response (RR = 1.62; 95% CI, 1.16 to 2.27) than tisa-cel among patients who underwent infusion. The OS from infusion onward comparing axi-cel to tisa-cel had a hazard ratio of 0.51 (95% CI, 0.31 to 0.83). The indirect comparison showed a higher rate of grade 1 to 2 cytokine release syndrome (CRS) in ZUMA-1 compared with JULIET (RR = 2.03; 95% CI, 1.55 to 2.65) and similar rates of grade ≥3 CRS and neurologic events. In the absence of a direct head-to-head study, the MAIC statistical technique suggests axi-cel may have superior efficacy but a greater risk of grade 1 to 2 CRS. Future real-world studies can further inform the relative efficacy and safety of CAR T therapies in RR-LBCL.
阿基仑赛（axi-cel）和Tisagenlecleucel（tisa-cel）是两种用于治疗复发/难治性大 B 细胞淋巴瘤（RR-LBCL）患者的自体抗 CD19 嵌合抗原受体 T（CAR T）细胞疗法。这两种疗法都可以诱导持久的缓解，但由于研究设计的差异，进行直接比较很困难。在这项研究中，使用匹配调整间接比较（MAIC）对 axi-cel 和 tisa-cel 的注册试验进行了比较。MAIC 用于调整试验之间患者特征的差异。使用患者水平数据对 ZUMA-1（axi-cel）试验的估计值进行调整，以匹配 JULIET（tisa-cel）研究人群的关键变量：国际预后指数、东部合作肿瘤组评分、分期、难治性或复发性疾病、双/三重打击状态、细胞起源和先前治疗线的数量。分析的终点是反应、总生存（OS）和不良事件。在调整试验之间患者特征的差异后，与 tisa-cel 相比，接受输注的患者中 axi-cel 与更高的客观缓解率（相对风险 [RR]=1.61；95%置信区间 [CI]，1.29 至 2.01）和完全缓解（RR=1.62；95%CI，1.16 至 2.27）相关。从输注开始比较 axi-cel 与 tisa-cel 的 OS 具有 0.51（95%CI，0.31 至 0.83）的风险比。间接比较显示，ZUMA-1 中 1 至 2 级细胞因子释放综合征（CRS）的发生率高于 JULIET（RR=2.03；95%CI，1.55 至 2.65），而≥3 级 CRS 和神经事件的发生率相似。在没有直接头对头研究的情况下，MAIC 统计技术表明 axi-cel 可能具有更高的疗效，但 1 至 2 级 CRS 的风险更高。未来的真实世界研究可以进一步了解 RR-LBCL 中 CAR T 疗法的相对疗效和安全性。
