Deschênes-Simard Xavier, Bromberg Maria, Devlin Sean M, Gonen Mithat, Beyar-Katz Ofrat, Ip Andrew, Marcus Ronit, Avigdor Abraham, Ballweg Annamaria, Rabinovich Emma, Alhomoud Mohammad, Rivas-Delgado Alfredo, Corona De Lapuerta Magdalena, Luna De Abia Alejandro, Palomba M Lia, Shah Gunjan L, Lin Richard J, Boardman Alexander P, Falchi Lorenzo, Lue Jennifer K, Salles Gilles A, Perales Miguel-Angel, Shouval Roni, Dahi Parastoo B, Scordo Michael
Univertity of Montreal, Canada.
Memorial Sloan Kettering Cancer Center (MSKCC), New York, New York, United States.
Blood Adv. 2025 Aug 15. doi: 10.1182/bloodadvances.2025016778.
Although 3 commercial CD19-targeted CAR T-cell therapies are available for large B-cell lymphoma (LBCL), no randomized clinical trials have compared their efficacy and safety. In this retrospective multicenter cohort study, we evaluated real-world clinical outcomes of patients with relapsed/refractory LBCL treated with axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel). Between April 2016 and July 2024, 624 patients received CD19-targeted CAR T-cell therapies (344 axi-cel, 142 tisa-cel, and 138 liso-cel). At a median follow-up of 20.9 months, estimated 2-year PFS and OS rates were 46%/63% for axi-cel, 30%/45% for tisa-cel, and 45%/58% for liso-cel. After adjusting for potential confounders in multivariable analyses, tisa-cel was associated with inferior progression-free survival (PFS) (hazard ratio [HR] = 2.25; 95% confidence interval [CI]: 1.65-3.06; p < 0.001) and overall survival (OS) (HR = 1.68; 95% CI: 1.19-2.36; p = 0.003) compared to axi-cel. No significant survival differences were found between liso-cel and axi-cel. Propensity score and subanalyses of patients treated in the second-line vs. third-line or later settings yielded similar outcomes. Compared to axi-cel, the objective response rate at 100 days was higher for liso-cel (odds ratio [OR] = 2.31; 95% CI: 1.21-4.80; p = 0.016) and lower for tisa-cel (OR = 0.36; 95% CI: 0.23-0.57; p < 0.001). Rates of CRS, ICANS, ICAHT, and febrile neutropenia were significantly higher with axi-cel. However, no significant differences in the cumulative incidence of infections or non-relapse mortality were found. Axi-cel was associated with faster vein-to-vein time (axi-cel: 35 days, tisa-cel: 43 days, liso-cel: 41 days; p < 0.001) and fewer out-of-specification products (axi-cel: 2%, tisa-cel: 4%, liso-cel: 11%; p = 0.004). These results provide insights into potential differential outcomes depending on product selection.
虽然有3种商业化的靶向CD19的嵌合抗原受体（CAR）T细胞疗法可用于治疗大B细胞淋巴瘤（LBCL），但尚无随机临床试验对它们的疗效和安全性进行比较。在这项回顾性多中心队列研究中，我们评估了接受阿基仑赛注射液（axi-cel）、替雷利珠单抗注射液（tisa-cel）或瑞基奥仑赛注射液（liso-cel）治疗的复发/难治性LBCL患者的真实世界临床结局。2016年4月至2024年7月期间，624例患者接受了靶向CD19的CAR T细胞疗法（344例接受axi-cel，142例接受tisa-cel，138例接受liso-cel）。中位随访20.9个月时，axi-cel的估计2年无进展生存期（PFS）和总生存期（OS）率分别为46%/63%，tisa-cel为30%/45%，liso-cel为45%/58%。在多变量分析中对潜在混杂因素进行校正后，与axi-cel相比，tisa-cel的无进展生存期（PFS）较差（风险比[HR]=2.25；95%置信区间[CI]：1.65-3.06；p<0.001），总生存期（OS）也较差（HR=1.68；95%CI：1.19-2.36；p=0.003）。liso-cel与axi-cel之间未发现显著的生存差异。倾向评分以及二线与三线或更晚期治疗患者的亚组分析得出了相似的结果。与axi-cel相比，liso-cel在100天时的客观缓解率更高（优势比[OR]=2.31；95%CI：1.21-4.80；p=0.016），tisa-cel则较低（OR=0.36；95%CI：0.23-0.57；p<0.001）。axi-cel的细胞因子释放综合征（CRS）、免疫效应细胞相关神经毒性综合征（ICANS）、免疫效应细胞相关血细胞减少症（ICAHT）和发热性中性粒细胞减少症的发生率显著更高。然而，在感染或非复发死亡率的累积发生率方面未发现显著差异。axi-cel的静脉到静脉时间更快（axi-cel：35天，tisa-cel：43天，liso-cel：41天；p<0.001），且不符合规格的产品更少（axi-cel：2%，tisa-cel：4%，liso-cel：11%；p=0.004）。这些结果为根据产品选择可能产生的不同结局提供了见解。
