O'Reilly Maeve A, Wilson William, Burns David, Kuhnl Andrea, Seymour Frances, Uttenthal Ben, Besley Caroline, Alajangi Rajesh, Creasey Thomas, Paneesha Shankara, Elliot Johnathon, Gonzalez Arias Carlos, Iyengar Sunil, Wilson Matthew R, Delaney Alison, Rubio Lourdes, Lambert Jonathan, Begg Khalil, Boyle Stephen, Cheok Kathleen P L, Collins Graham P, Roddie Claire, Johnson Rod, Sanderson Robin
University College London Hospital London UK.
University College London Cancer Institute London UK.
Hemasphere. 2024 Jun 13;8(6):e87. doi: 10.1002/hem3.87. eCollection 2024 Jun.
Brexucabtagene autoleucel (brexu-cel) is an autologous CD19 CAR T-cell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMA-2, brexu-cel demonstrated impressive responses in patients failing ≥2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our real-world intention-to-treat (ITT) outcomes for brexu-cel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability. Of 119 approved, 104 underwent leukapheresis and 83 received a brexu-cel infusion. Progressive disease (PD) and/or manufacturing (MF) were the most common reasons for failure to reach harvest and/or infusion. For infused patients, best overall and complete response rates were 87% and 81%, respectively. At a median follow-up of 13.3 months, median progression-free survival (PFS) for infused patients was 21 months (10.1-NA) with a 6- and 12-month PFS of 82% (95% confidence interval [CI], 71-89) and 62% (95% CI, 49-73), respectively. ≥Grade 3 cytokine release syndrome and neurotoxicity occurred in 12% and 22%, respectively. On multivariate analysis, inferior PFS was associated with male sex, bulky disease, ECOG PS > 1 and previous MF. Cumulative incidence of non-relapse mortality (NRM) was 6%, 15%, and 25% at 6, 12, and 24 months, respectively, and mostly attributable to infection. Outcomes for infused patients in the UK are comparable to ZUMA-2 and other real-world reports. However, ITT analysis highlights a significant dropout due to PD and/or MF. NRM events warrant further attention.
布雷西尤单抗（brexu-cel）是一种自体CD19嵌合抗原受体T细胞产品，已被批准用于复发/难治性（r/r）套细胞淋巴瘤（MCL）。在ZUMA-2试验中，brexu-cel在≥2线治疗失败的患者中表现出令人印象深刻的反应，这些患者包括使用过布鲁顿酪氨酸激酶抑制剂的患者，其总缓解率和完全缓解率分别为93%和67%。在此，我们报告了2021年2月至2023年6月期间，来自英国12家机构的连续、前瞻性批准的患者中brexu-cel的真实世界意向性治疗（ITT）结果，重点关注可行性、疗效和耐受性。在119名获批患者中，104名接受了白细胞分离术，83名接受了brexu-cel输注。疾病进展（PD）和/或生产问题（MF）是未能进行采集和/或输注的最常见原因。对于接受输注的患者，最佳总缓解率和完全缓解率分别为87%和81%。在中位随访13.3个月时，接受输注患者的中位无进展生存期（PFS）为21个月（10.1-无上限），6个月和12个月的PFS分别为82%（95%置信区间[CI]，71-89）和62%（95%CI，49-73）。≥3级细胞因子释放综合征和神经毒性的发生率分别为12%和22%。多因素分析显示，较差的PFS与男性、大包块疾病、东部肿瘤协作组（ECOG）体能状态评分>1以及既往MF有关。非复发死亡率（NRM）在6个月、12个月和24个月时的累积发生率分别为6%、15%和25%，主要归因于感染。英国接受输注患者的结果与ZUMA-2试验及其他真实世界报告相当。然而，ITT分析突出显示由于PD和/或MF导致显著失访。NRM事件值得进一步关注。
