CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Identification of an optimal absolute lymphocyte count at leukapheresis in patients with lymphoma treated with CART.
Identification of an optimal absolute lymphocyte count at leukapheresis in patients with lymphoma treated with CART.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
计划接受 CAR-T(CAR-T 细胞疗法)的大B细胞淋巴瘤(LBCL)患者中,T细胞适应性可能受损。尽管已显示白细胞采集时的绝对淋巴细胞计数(ALC)与接受 axicabtagene ciloleucel(axi-cel)治疗的 LBCL 患者结局相关,但尚未确定阈值。这是一项多中心回顾性研究,包括1个 axi-cel 训练和验证队列,以及1个混合产品验证队列。采用变化点方法确定与最佳无进展生存期(PFS)相关的 ALC 阈值。axi-cel 训练队列纳入379例患者。ALC 作为连续变量与第30天完全缓解相关(中位数,0.79 × 10 3 /μL vs 0.63 × 10 3 /μL;P = .004)。
确定 ALC 为0.34 × 10 3 /μL 是 PFS 的最佳阈值(7 vs 3个月;P = .0013)。该关联在 axi-cel 验证队列中得到证实(165例患者;19.8 vs 3.5个月;P = .04),但在混合验证队列中未得到证实(163例患者;5 vs 1.5个月;P = .3)。在单变量分析中,与 ALC 高于阈值相关的特征包括低国际预后指数评分(P = .02)、低血清 C 反应蛋白水平(P = .02)、低血清铁蛋白水平(P < .001)以及既往系统性治疗线数较少(P = .02)。采集时 ALC >0.34 × 10 3 /μL 与接受 axi-cel 治疗的 LBCL 患者最佳结局相关。有必要进一步研究既往治疗对采集时淋巴细胞数量和表型的影响。
T-cell fitness can be impaired in patients with large B-cell lymphoma (LBCL) planned for CART (chimeric antigen receptor T-cell therapy). Although absolute lymphocyte count (ALC) at the time of leukapheresis has been shown to associate with outcomes in patients with LBCL treated axicabtagene ciloleucel (axi-cel), no threshold has been identified. This is a multicenter retrospective study including 1 axi-cel training and validation cohort, and 1 mixed-product validation cohort. The change-point method was used to identify an ALC threshold associating with optimal progression-free survival (PFS). Three hundred seventy-nine patients were included in the axi-cel training cohort. ALC as a continuous variable was associated with complete response on day 30 (median, 0. 79 × 10 3 /μL vs 0. 63 × 10 3 /μL; P = . 004). An ALC of 0.
34 × 10 3 /μL was identified as the optimal threshold for PFS (7 vs 3 months; P = . 0013). The association was confirmed in the axi-cel validation cohort (165 patients; 19. 8 vs 3. 5 months; P = . 04) but not in the mixed validation cohort (163 patients; 5 vs 1. 5 months; P = . 3). On univariate analysis, characteristics associated with ALC above the threshold included low International Prognostic Index score ( P = .
02), low serum C-reactive protein level ( P = . 02), low serum ferritin level ( P < . 001), and low number of prior lines of systemic therapy ( P = . 02). An ALC of >0. 34 × 10 3 /μL at the time of apheresis is associated with optimal outcomes in patients with LBCL treated with axi-cel. A deeper investigation of the impact of prior therapies on the number and phenotype of lymphocytes at time of apheresis is warranted.
在 PubMed 查看 → 出版商原文(DOI) 全文 PDF(PMC)· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
MEMBER ACCOUNT
登录成功会直接打开下一页。