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基于里程碑分析的大 B 细胞淋巴瘤 CD19 CAR-T 细胞治疗后长期结局评估

英文原题:Landmark-Based Evaluations of Long-Term Outcomes After CD19 CAR T-Cell Therapy in Large B-Cell Lymphoma.

查看英文原题

Landmark-Based Evaluations of Long-Term Outcomes After CD19 CAR T-Cell Therapy in Large B-Cell Lymphoma.

PubMed 2026/02/28(内容时间) Transplant Cell Ther Q1 · IF 4.7(JCR 2025)

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中文摘要

CAR-T 细胞疗法已改变复发/难治性大B细胞淋巴瘤(LBCL)的治疗格局,但持久缓解仍具挑战性。在这项回顾性多中心研究中,479例接受商业化CD19 CAR-T 产品治疗的LBCL患者——axicabtagene ciloleucel(axi-cel,n = 262)、tisagenlecleucel(tisa-cel,n = 131)和lisocabtagene maraleucel(liso-cel,n = 86)——通过系列landmark分析进行评估,中位随访时间分别为23、34和16个月。在输注后第28天以及3、6、12、18和24个月评估无进展生存期(PFS),以确定复发风险何时下降并实现持续无病缓解。

在早期时间点达到完全缓解(CR)的患者PFS显著改善。在多变量分析中,淋巴细胞清除前乳酸脱氢酶(LDH)水平升高在多个landmark时间点与较差的PFS独立相关(第28天HR 2.67,P < .001;3个月HR 1.83,P = .044;6个月HR 2.19,P = .016),并在这些相同时间点显示与较差的总体生存期(OS)一致相关。累积复发和非复发死亡(NRM)估计支持持续CR的预后价值。这项基于landmark的分析增进了对CAR-T 细胞疗法后持久缓解动力学的理解,提示有治愈趋势,但仍需更长时间随访以确认持久缓解。

展开英文摘要原文

CAR T-cell therapy has transformed relapsed/refractory large B-cell lymphoma (LBCL) treatment, yet durable remissions remain challenging. In this retrospective multicenter study, 479 LBCL patients treated with commercial CD19 CAR-T products, axicabtagene ciloleucel (axi-cel, n = 262), tisagenlecleucel (tisa-cel, n = 131), and lisocabtagene maraleucel (liso-cel, n = 86), were evaluated using serial landmark analyses, with median follow-ups of 23, 34, and 16 months, respectively. Progression-free survival (PFS) was assessed at Day 28 and at 3, 6, 12, 18 and 24 months post-infusion to determine when relapse risk declines and sustained disease-free remission is achieved.

Patients who attained a complete response (CR) at early time points had significantly improved PFS. In multivariable analyses, elevated pre-lymphodepletion lactate dehydrogenase (LDH) levels were independently associated with inferior PFS across several landmarks (HR 2. 67, P < . 001 at Day 28; HR 1. 83, P = . 044 at 3 months; HR 2. 19, P = .

016 at 6 months) and showed consistent association with inferior overall survival (OS) at these same time points. Cumulative relapse and non-relapse mortality (NRM) estimates supported the prognostic value of sustained CR. This landmark-based analysis advances understanding of durable remission kinetics following CAR T-cell therapy, indicating a trend toward cure, though longer follow-up is needed to confirm durable remission.

论文信息

作者
Gomez-Llobell M、Shouval R、Brown S、Goan-Accav N、Devlin S、Corona M、Rejeski K、Rivas-Delgado A
第一作者单位
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Universidad Complutense de Madrid, Madrid, Spain.United States
通讯作者单位
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Universidad Complutense de Madrid, Madrid, Spain. Electronic address: peralesm@mskcc.org.United States
文献类型
多中心研究
期刊
Transplantation and cellular therapy2026 Jun
原文标识
PubMed 41765136 · DOI 10.1016/j.jtct.2026.02.058