CD19 CAR-T treatment shows limited efficacy in r/r DLBCL with double expression and TP53 alterations

IF 3.7 3区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotherapy Pub Date : 2024-07-25 DOI:10.1016/j.jcyt.2024.07.011

Bin Xue , Yifan Liu , Jie Zhou , Lili Zhou , Shiguang Ye , Yan Lu , Wenjun Zhang , Bing Xiu , Aibin Liang , Ping Li , Ying Lu , Wenbin Qian , Xiu Luo

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引用次数: 0

Abstract

Object

Autologous CD19 chimeric antigen receptor T-cell therapy (CAR-T) significantly modifies the natural course of chemorefractory diffuse large B-cell lymphoma (DLBCL). However, 25% to 50% of patients with relapsed/refractory DLBCL still do not achieve remission. Therefore, investigating new molecular prognostic indicators that affect the effectiveness of CAR-T for DLBCL and developing novel combination therapies are crucial.

Methods

Data from 73 DLBCL patients who received CD19 CAR-T (Axi-cel or Relma-cel) were retrospectively collected from Shanghai Tongji Hospital of Tongji University, The Second Affiliated Hospital Zhejiang University School of Medicine, and The Affiliated People's Hospital of Ningbo University. Prior to CD19 CAR-T-cell transfusions, the patients received fludarabine and cyclophosphamide chemotherapy regimen.

Results

Our study revealed that relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) patients with both Double-expression (MYC > 40% and BCL2 > 50%) and TP53 alterations tend to have a poorer clinical prognosis after CAR-T therapy, even when CAR-T therapy is used in combination with other therapies. However, CAR-T therapy was found to be effective in patients with only TP53 alterations or DE status, suggesting that their prognosis is in line with that of patients without TP53 alterations or DE status.

Conclusions

Our study suggests that r/r DLBCL patients with both DE status and TP53 alterations treated with CAR-T therapy are more likely to have a poorer clinical prognosis. However, CAR-T therapy has the potential to improve the prognosis of patients with only TP53 alterations or DE status to be similar to that of patients without these abnormalities.

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CD19 CAR-T疗法对有双重表达和TP53改变的r/r DLBCL疗效有限

目标自体CD19嵌合抗原受体T细胞疗法（CAR-T）能显著改变化疗难治性弥漫大B细胞淋巴瘤（DLBCL）的自然病程。然而，复发/难治性弥漫大B细胞淋巴瘤患者中仍有25%至50%的患者无法获得缓解。方法回顾性收集了同济大学附属上海同济医院、浙江大学医学院附属第二医院和宁波大学附属人民医院的73例接受CD19 CAR-T（Axi-cel或Relma-cel）治疗的DLBCL患者的数据。结果我们的研究发现，复发/难治性弥漫大B细胞淋巴瘤（r/r DLBCL）患者如果同时存在双表达（MYC表达40%，BCL2表达50%）和TP53改变，即使CAR-T疗法与其他疗法联合使用，其临床预后也会较差。然而，CAR-T疗法对仅有TP53改变或DE状态的患者有效，这表明他们的预后与无TP53改变或DE状态的患者一致。结论我们的研究表明，同时具有DE状态和TP53改变的r/r DLBCL患者接受CAR-T疗法治疗后，临床预后更可能较差。然而，CAR-T疗法有可能改善仅有TP53改变或DE状态的患者的预后，使其与无这些异常的患者的预后相似。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytotherapy 医学-生物工程与应用微生物

CiteScore

6.30

自引率

4.40%

发文量

683

审稿时长

49 days

期刊介绍： The journal brings readers the latest developments in the fast moving field of cellular therapy in man. This includes cell therapy for cancer, immune disorders, inherited diseases, tissue repair and regenerative medicine. The journal covers the science, translational development and treatment with variety of cell types including hematopoietic stem cells, immune cells (dendritic cells, NK, cells, T cells, antigen presenting cells) mesenchymal stromal cells, adipose cells, nerve, muscle, vascular and endothelial cells, and induced pluripotential stem cells. We also welcome manuscripts on subcellular derivatives such as exosomes. A specific focus is on translational research that brings cell therapy to the clinic. Cytotherapy publishes original papers, reviews, position papers editorials, commentaries and letters to the editor. We welcome "Protocols in Cytotherapy" bringing standard operating procedure for production specific cell types for clinical use within the reach of the readership.