决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:TP53-Altered Aggressive Large B-Cell Lymphoma (LBCL) Outcomes by Treatment Modality: A Multicenter Cohort From 14 US Centers.
我们的研究结果表明,TP53改变的LBCL可通过一线根治性化疗免疫治疗治愈。
大B细胞淋巴瘤(LBCL)治疗的进展已将治疗选择从传统化学免疫治疗扩展到细胞治疗和靶向治疗。基于组织病理学和分子特征,识别可能从这些新方法中获益的LBCL亚群引起了越来越多的兴趣。分子亚分类已鉴定出一种以TP53改变为特征的LBCL A53表型,该亚组在历史上与标准治疗后不良预后相关。为了更好地定义当代治疗时代TP53改变LBCL的无进展生存和总生存结局,我们开展了一项多中心队列研究,评估对一线、二线和三线治疗的反应。我们的研究结果表明,TP53改变的LBCL可通过一线治愈性化学免疫治疗治愈。在二线和三线设置中,不同治疗方法之间的结局无显著差异,尽管在双打击患者中二线使用CAR-T观察到PFS改善。本研究代表了已报道的最大TP53改变LBCL患者队列,并为新型药物时代各线治疗的治疗结局提供了重要见解。
Advances in the treatment of large B-cell lymphoma (LBCL) have expanded therapeutic options beyond conventional chemoimmunotherapy to include cellular and targeted therapies. There is growing interest in identifying subsets of LBCL that may benefit from these novel approaches based on histopathologic and molecular features. Molecular subclassification has identified an LBCL A53 phenotype characterized by TP53 alterations, a subgroup historically associated with poor outcomes following standard therapy. To better define progression-free and overall survival outcomes in TP53-altered LBCL in the contemporary treatment era, we conducted a multicenter cohort study evaluating responses to first-, second-, and third-line therapies. Our findings demonstrate that TP53-altered LBCL can be cured with first-line curative intent chemoimmunotherapy. In the second and third-line setting, outcomes did not significantly differ between different treatment approaches, though improved PFS was seen with CAR-T in the second line for double hit patients. This study represents the largest reported cohort of patients with TP53-altered LBCL and provides important insights into treatment outcomes across lines of therapy in the era of novel agents.
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