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