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:Outcomes of CD19 CAR-T therapy in central nervous system lymphoma: Insights from a multicentre experience.
Outcomes of CD19 CAR-T therapy in central nervous system lymphoma: Insights from a multicentre experience.
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。
嵌合抗原受体(CAR)T细胞疗法重塑了复发/难治性(R/R)弥漫大B细胞淋巴瘤(DLBCL)的治疗格局。然而,其在中枢神经系统淋巴瘤(CNSL)中的作用仍不明确。
我们开展了一项多中心、回顾性研究,纳入54例在四家国际机构接受商业化(axi-cel、tisa-cel、liso-cel)或即时制备(POC)CD19-CAR-T 细胞产品治疗的成人R/R CNSL患者。在CAR-T 输注后第100天,65%的患者在全身和中枢神经系统两个部位均达到完全缓解,作为其最佳疗效。中位无进展生存期(PFS)为7.5个月,1年PFS为35%。中位总生存期(OS)为19个月,1年OS为63%。在多变量分析中,CAR-T 产品与PFS(p = 0.009)和OS(p = 0.013)显著相关,接受tisa-cel的患者预后差于axi-cel,而接受liso-cel或POC CAR-T 产品的患者预后优于axi-cel。毒性特征与R/R DLBCL的关键性试验一致。3级细胞因子释放综合征发生于11%的患者,而3级免疫效应细胞相关神经毒性综合征见于28%。
我们的研究支持抗CD19 CAR-T 疗法在CNSL中的可行性和安全性。所输注的具体CAR-T 产品是影响结局的一个因素。
Chimeric antigen receptor (CAR) T-cell therapy has reshaped the treatment paradigm for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
However, its role in central nervous system lymphoma (CNSL) remains uncertain.
We conducted a multicentre, retrospective study on 54 adult R/R CNSL patients treated at four international institutions with commercial (axi-cel, tisa-cel, liso-cel) or a point of care (POC) CD19-CAR T-cell products. At day 100 post CAR-T infusion, 65% of patients attained a complete response as their best response in both systemic and central nervous system compartments. The median progression-free survival (PFS) was 7. 5 months, with a 1-year PFS of 35%. The median overall survival (OS) was 19 months, with a 1-year OS of 63%.
In multivariable analyses, CAR-T product was significantly associated with PFS (p = 0. 009) and OS (p = 0. 013), with patients receiving tisa-cel exhibiting poorer outcomes than axi-cel and patients receiving liso-cel or POC CAR-T product demonstrating better outcomes than axi-cel. Toxicity profiles were consistent with pivotal trials in R/R DLBCL. Grade 3 cytokine release syndrome occurred in 11% of patients, while grade 3 immune-effector cell-associated neurotoxicity syndrome was observed in 28%.
Our study supports the feasibility and safety of anti-CD19 CAR-T therapy in CNSL. The specific CAR-T product infused emerged as a factor influencing outcomes.
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