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:TP53 mutations and baseline lymphocytes indicate response to glofitamab in relapsed or refractory diffuse large B-cell lymphoma.
TP53 mutations and baseline lymphocytes indicate response to glofitamab in relapsed or refractory diffuse large B-cell lymphoma.
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CAR-T 细胞疗法已成为复发/难治性(R/R)弥漫性大 B 细胞淋巴瘤(DLBCL)的一种有希望的治疗选择,但制备时间长、费用高和毒性限制其临床应用。包括 glofitamab 在内的 T 细胞衔接剂(TCE)可能满足这些未竟需求,但真实世界数据仍稀少。这项真实世界研究(NCT06481826)纳入 30 名中国患者。既往治疗线数中位数为 2(范围 2–5),90% 患者既往未接受 CAR-T。中位随访 15 个月后,总缓解率(ORR)为 66.7%。1 年无进展生存率(PFS)为 62.5%,中位 PFS 为 15 个月;1 年总生存率(OS)为 70%。单因素分析确定,结外受累部位超过 1 处、TP53 突变和基线淋巴细胞偏低是预后不良因素。安全性可管理:43.3% 患者发生细胞因子释放综合征(CRS,主要为 1–3 级),3.3% 患者发生 1 级免疫效应细胞相关神经毒性综合征(ICANS)。血液学毒性多为轻度。20% 患者发生 COVID-19 感染。
本研究显示 glofitamab 对中国 R/R DLBCL 患者有效且耐受性良好。更早治疗可能获益更大;仍需扩大队列,进一步评估其在多处结外病灶、TP53 突变和基线淋巴细胞较低患者中的疗效。
Although CAR-T cell therapy has emerged as a promising therapeutic option for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), long manufacturing time, high cost and toxicities limit its clinical use. T-cell engagers (TCEs) including glofitamab may address these unmet needs, but real-world data remain scarce. This real-world study (NCT06481826) enrolled 30 Chinese patients. The median prior treatment lines were 2 (2-5) and 90% had no prior CAR-T therapy. After a median follow-up of 15 months, the overall response rate (ORR) was 66.
7%. The 1-year progression-free survival (PFS) was 62. 5% with a median PFS of 15 months. The 1-year overall survival (OS) was 70%. Univariate analysis identified more than 1 extranodal involvement site, TP53 mutation and low baseline lymphocytes as poor prognostic factors. Safety profile was manageable. 43. 3% patients developed cytokine release syndrome (CRS, mostly grade 1-3) and 3. 3% had grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). The hematologic toxicity was mostly mild. COVID-19 infection occurred in 20% of patients.
This study demonstrates that glofitamab is effective and well-tolerated in Chinese R/R DLBCL patients. Earlier lines of glofitamab may be more beneficial, while expanded cohorts are warranted to explore its efficacy among patients with multiple extranodal lesions, TP53 mutations and low baseline lymphocytes.
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