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:Clinical outcome and immunophenotype of axicabtagene ciloleucel (axi-cel) and relmacabtagene autoleucel (relma-cel) in relapsed/refractory large B-Cell lymphoma on Chinese population: a single-center experience.
Clinical outcome and immunophenotype of axicabtagene ciloleucel (axi-cel) and relmacabtagene autoleucel (relma-cel) in relapsed/refractory large B-Cell lymphoma on Chinese population: a single-center experience.
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在该队列中,用于 r/r 大 B 细胞淋巴瘤的 CAR-T 治疗取得了高缓解率和令人鼓舞的生存结局,其中 axi-cel 相比 relma-cel 疗效更优,但 CRS 发生率更高。
靶向CD19的嵌合抗原受体(CAR)T细胞疗法治疗复发/难治性(r/r)大B细胞淋巴瘤疗效显著,因此阿基仑赛(axi-cel)和瑞基奥仑赛(relma-cel)已在中国获批。尽管取得这些进展,CAR-T 在亚洲人群中的真实世界数据仍有限,axi-cel与relma-cel的比较结局也研究不足。
本回顾性队列研究分析中国一家三级医院33例r/r大B细胞淋巴瘤患者接受商业化CD19 CAR-T 治疗的真实世界疗效和安全性。收集基线人口学特征、国际预后指数(IPI)评分、体能状态和遗传学特征;并在部分患者中评估CAR-T 制备前后的T细胞免疫表型,探讨其与临床结局的潜在关联。通过PET/CT评估临床应答,采用Kaplan-Meier方法分析生存。
33例患者中位年龄53岁,CAR-T 输注后3个月完全缓解率(CR)为76.7%。1年总生存率(OS)为72.3%,1年无进展生存率(PFS)为71.2%。T细胞表型分析显示,初始T细胞亚群与最终CAR-T 产品特征无显著关联。axi-cel的CR率高于relma-cel(100% vs 61.1%),但伴随更严重的细胞因子释放综合征(CRS)。relma-cel产品中干细胞样记忆T细胞(CCR7+ CD45RA+)比例较高的患者疗效较低,提示治疗获益可能存在一个理想的此类细胞比例范围。
本队列中,CAR-T 治疗r/r大B细胞淋巴瘤取得较高缓解率和良好生存结局;与relma-cel相比,axi-cel疗效更好,但CRS发生率更高。研究强调,CAR-T 产品需维持适宜的干细胞样记忆T细胞比例,以提高疗效。仍需前瞻性多中心研究在更大患者群体中验证这些发现。
Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has shown remarkable efficacy for treating relapsed or refractory (r/r) large B-cell lymphomas, leading to the approval of axicabtagene ciloleucel (axi-cel) and relmacabtagene autoleucel (relma-cel) in China. Despite these advances, limited real-world data exist for CAR-T therapies in Asian populations, and comparative outcomes between axi-cel and relma-cel remain understudied.
This retrospective cohort study analyzed real-world efficacy and safety data for commercial CD19 CAR-T therapies in 33 patients with r/r large B-cell lymphoma treated at a tertiary hospital in China. Baseline demographics, International Prognostic Index (IPI) scores, performance status, and genetic profiles were collected. Additionally, T-cell immunophenotypes were assessed in a subset of patients pre- and post-CAR-T manufacturing to evaluate potential associations with clinical outcomes. Clinical responses were measured using PET/CT, and survival was analyzed via Kaplan-Meier methods.
Among the 33 patients (median age 53), 76.7% achieved a complete response (CR) three months post-CAR-T infusion. One-year overall survival (OS) was 72.3%, and the one-year progression-free survival (PFS) was 71.2%. T-cell phenotype analysis revealed no significant association between initial T-cell subsets and final CAR-T product characteristics. Axi-cel demonstrated a higher CR rate (100%) compared to relma-cel (61.1%) but was associated with more severe cytokine release syndrome (CRS). Patients with a higher proportion of stem-like memory T cells (CCR7 + CD45RA+) in the relma-cel product exhibited reduced efficacy, suggesting an optimal range of stem-like memory cell proportions for therapeutic benefit.
In this cohort, CAR-T therapies for r/r large B-cell lymphoma yielded high response rates and promising survival outcomes, with axi-cel showing superior efficacy but higher CRS incidence compared to relma-cel. The study highlights the need for optimal stem-like memory T-cell proportions in CAR-T products for improved efficacy. Prospective multicenter studies are warranted to confirm these findings in larger patient populations.
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