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:CAR-T Cell Therapy Versus Salvage Chemotherapy in Relapsed/Refractory DLBCL: A Systematic Review and Meta-Analysis Integrating Radiologic, Laboratory, and Histopathologic Correlates.
CAR-T Cell Therapy Versus Salvage Chemotherapy in Relapsed/Refractory DLBCL: A Systematic Review and Meta-Analysis Integrating Radiologic, Laboratory, and Histopathologic Correlates.
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在 R/R DLBCL 中,CAR-T 治疗相比挽救性化疗可提供更优的生存和缓解结局,尤其是在高危人群中。
复发/难治性弥漫性大B细胞淋巴瘤(R/R DLBCL)仍是重大治疗挑战,尤其是具有高危分子特征或原发难治性疾病的患者。CAR-T 细胞疗法已成为有前景的治疗策略,但其相较挽救化疗的比较疗效仍需全面评估。
本系统综述和荟萃分析遵循PRISMA 2020及MOOSE指南。纳入评估成人R/R DLBCL患者CAR-T 与挽救化疗的随机对照试验和高质量比较队列研究。主要结局为总生存期(OS)及无进展生存期(PFS);次要结局包括完全代谢缓解(CMR)、毒性谱及多学科相关因素(影像学、实验室和组织病理学)。采用随机效应模型、荟萃回归分析及GRADE评估。
共纳入8项研究(n=2150)。CAR-T 显著改善PFS(HR 0.55,95% CI 0.42–0.71;p<0.001)及OS(HR 0.68,95% CI 0.54–0.86;p=0.001)。CAR-T 组CMR率高于挽救化疗组(56.0%比24.5%;RR 2.28,95% CI 1.82–2.86;p<0.001)。炎症标志物升高及肿瘤负荷较高与免疫相关毒性风险增加相关。亚组分析显示,原发难治及双打击淋巴瘤患者获益更大。CAR-T 治疗相关细胞因子释放综合征发生率为9%(3级),ICANS为12%;而挽救化疗血液学毒性发生率更高。
与挽救化疗相比,CAR-T 治疗可改善R/R DLBCL患者生存和缓解结局,尤其适用于高危人群。整合影像学、实验室及分子预测因子,可能有助于优化患者选择和毒性管理。
Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) remains a major therapeutic challenge, particularly among patients with high-risk molecular features or primary refractory disease. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising treatment strategy; however, its comparative effectiveness versus salvage chemotherapy requires comprehensive evaluation.
This systematic review and meta-analysis were conducted in accordance with PRISMA 2020 and MOOSE guidelines. Randomized controlled trials and high-quality comparative cohort studies evaluating CAR-T therapy versus salvage chemotherapy in adult patients with R/R DLBCL were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included complete metabolic response (CMR), toxicity profiles, and multidisciplinary correlates (radiologic, laboratory, and histopathologic). Random-effects models, meta-regression analyses, and GRADE assessment were applied.
Eight studies (n = 2,150) were included. CAR-T therapy significantly improved PFS (HR 0.55, 95% CI 0.42-0.71; p < 0.001) and OS (HR 0.68, 95% CI 0.54-0.86; p = 0.001). CMR rates were higher in the CAR-T group (56.0%) compared with salvage chemotherapy (24.5%) (RR 2.28, 95% CI 1.82-2.86; p < 0.001). Elevated inflammatory markers and tumor burden were associated with increased risk of immune-related toxicities. Subgroup analyses demonstrated greater benefit in primary refractory and double-hit lymphoma. CAR-T therapy was associated with cytokine release syndrome (9% grade 3) and ICANS (12%), whereas salvage chemotherapy demonstrated higher rates of hematologic toxicity.
CAR-T therapy provides superior survival and response outcomes compared with salvage chemotherapy in R/R DLBCL, particularly in high-risk populations. Integration of radiologic, laboratory, and molecular predictors may enhance patient selection and optimize toxicity management.
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