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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Pre-Transplant MRD Negativity and Age Under 40 Predict Superior Long-Term Survival in Relapsed/Refractory B-ALL After CAR-T Therapy Bridging to Haploidentical HSCT: A Multicenter Retrospective Study With 6-Year Follow-Up.
Pre-Transplant MRD Negativity and Age Under 40 Predict Superior Long-Term Survival in Relapsed/Refractory B-ALL After CAR-T Therapy Bridging to Haploidentical HSCT: A Multicenter Retrospective Study With 6-Year Follow-Up.
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序贯异基因造血干细胞移植(allo-HSCT)是提高复发/难治性急性淋巴细胞白血病(R/R ALL)CAR-T 疗效的重要策略,但 CAR-T 后接受 allo-HSCT 的长期生存率仍有争议。研究团队此前报告了 122 名接受抗 CD19 CAR-T 后达到微小残留病(MRD)阴性完全缓解(CR)的 R/R B-ALL 患者结局,其中 67 人未进一步移植(非移植组),55 人随后接受单倍体相合造血干细胞移植(移植组)。本文报告该队列的延长随访结果,中位随访 72.9 个月。与非移植组相比,移植组 5 年无白血病生存率(LFS;50.5% 对 25.7%,p<0.001)和总生存率(OS;53.5% 对 25.6%,p<0.001)更高。
多变量分析显示,移植时 MRD 阳性是 LFS 和 OS 较差以及复发累积发生率(CIR)较高的独立相关因素。移植前 MRD 阴性患者(MRD−组)的 5 年 CIR 低于 MRD 阳性患者(MRD+组)(20.8% 对 50.0%,p=0.014)。MRD+组和 MRD−组的 5 年 LFS 分别为 26.7% 和 59.4%(p=0.003);MRD−组 5 年 OS 高于 MRD+组(62.0% 对 30.5%,p=0.006)。CAR-T 后达到 CR 的患者若移植前 MRD 阴性,接受单倍体相合移植与更好的长期生存相关。但感染成为一项重要并发症,可能削弱长期生存获益。临床试验注册:ClinicalTrials.gov,编号 ChiCTR1900023957。
Sequential allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a critical approach to enhance the efficacy of chimeric antigen receptor T cell (CAR-T) therapy for relapsed/refractory acute lymphoblastic leukemia (R/R ALL). The long-term survival rates following allo-HSCT after CAR-T cell therapy remain controversial.
We previously reported the results of 122 patients with R/R B-ALL who achieved minimal residual disease negative (MRD-) complete remission (CR) after anti-CD19 CAR-T, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haplo-HSCT (transplant group).
Here, we present the extended follow-up of this cohort, with a median of 72. 9 months. Compared with the non-transplant group, transplantation recipients had a higher 5-year LFS (50. 5% vs. 25. 7%; p < 0. 001) and OS (53. 5% vs. 25. 6%; p < 0. 001). Multivariable analysis identified MRD positivity at transplantation as an independent factor associated with worse LFS, OS, and a higher cumulative incidence rate of relapse (CIR).
MRD-negative patients before transplant (MRD- group) had a lower 5-year CIR compared to MRD-positive patients (MRD+ group) (20. 8% vs. 50. 0%; p = 0. 014). The 5-year LFS rates in the MRD+ and MRD- groups were 26. 7% and 59. 4%, respectively (p = 0. 003). The 5-year OS of the MRD- group was higher than that of the MRD+ group (62. 0% vs. 30. 5%; p = 0. 006). For patients who achieve CR after CAR-T therapy, haplo-HSCT with pre-transplant MRD negativity was associated with better long-term survival.
However, infections emerged as a significant complication that may reduce the long-term survival benefits. Trial Registration: ClinicalTrials. gov identifier: ChiCTR1900023957.
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