决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Outcomes of patients over 70 years treated with brexu-cel for R/R mantle cell lymphoma: a study from the CTIWP of EBMT.
Outcomes of patients over 70 years treated with brexu-cel for R/R mantle cell lymphoma: a study from the CTIWP of EBMT.
这项回顾性真实世界分析评估了2020年至2024年间接受brexu-cel治疗并报告至EBMT registry的年龄≥70岁的R/R MCL患者。
套细胞淋巴瘤(MCL)主要影响老年人,复发/难治性(R/R)疾病的治疗选择仍然有限。Brexucabtagene autoleucel(brexu-cel)在R/R MCL中显示出高疗效,但在老年人群中的数据稀缺。这项回顾性、真实世界分析评估了2020年至2024年间在EBMT注册中心报告的接受brexu-cel治疗的年龄≥70岁R/R MCL患者。共纳入来自13个国家96个中心的233例患者(输注时中位年龄,74.6岁;44%>75岁)。大多数患者东部肿瘤协作组(ECOG)评分为0至1(89%),且接受过大量既往治疗;62%有既往Bruton酪氨酸激酶抑制剂暴露。在第+100天,最佳总体缓解为完全缓解78%,部分缓解13%。在30天时,任何级别细胞因子释放综合征的累积发生率为80%(≥3级,9%),免疫效应细胞相关神经毒性综合征为57%(≥3级,22%)。在1年时,总生存(OS)为74%;无进展生存(PFS)为62%;复发/进展发生率为25%;非复发死亡(NRM)为13%。年龄>75岁患者的结局与70至75岁患者相当。在多变量分析中,ECOG≥2仍是不良OS(风险比[HR],4.50;P< .001)和PFS(HR,3.10;P< .001)的最强预测因素,而年龄与结局无独立相关性。Brexu-cel在年龄≥70岁R/R MCL患者中有效,尽管NRM发生率相对较高,仍实现了高缓解率和有意义的生存。功能状态而非年龄应指导资格判定。
Mantle cell lymphoma (MCL) predominantly affects older adults, and treatment options for relapsed/refractory (R/R) disease remain limited. Brexucabtagene autoleucel (brexu-cel) has demonstrated high efficacy in R/R MCL, but data in older adult populations are scarce. This retrospective, real-world analysis evaluated patients aged ≥70 years with R/R MCL treated with brexu-cel and reported to the EBMT registry between 2020 and 2024. A total of 233 patients from 96 centers across 13 countries were included (median age at infusion, 74.6 years; 44% >75 years). Most had Eastern Cooperative Oncology Group (ECOG) 0 to 1 (89%) and were heavily pretreated; 62% had prior Bruton tyrosine kinase inhibitor exposure. At day +100, the best overall response was complete remission in 78% and partial remission in 13%. At 30 days, the cumulative incidence of any-grade cytokine release syndrome was 80% (grade ≥3, 9%) and immune effector cell-associated neurotoxicity syndrome was 57% (grade ≥3, 22%). At 1 year, overall survival (OS) was 74%; progression-free survival (PFS), 62%; relapse/progression incidence, 25%; and nonrelapse mortality (NRM), 13%. Patients aged >75 years had outcomes comparable with those aged 70 to 75 years. In multivariable analysis, ECOG ≥2 remained the strongest predictor of inferior OS (hazard ratio [HR], 4.50; P< .001) and PFS (HR, 3.10; P< .001), whereas age was not independently associated with outcomes. Brexu-cel is effective in patients aged ≥70 years with R/R MCL, achieving high remission rates and meaningful survival, despite a relatively high incidence of NRM. Functional status, rather than age, should guide eligibility.
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