自体 CD19 嵌合抗原受体 T 细胞疗法 (CAR-T) 显着改变化学难治性弥漫性大 B 细胞淋巴瘤 (DLBCL) 的自然病程。然而，25% 至 50% 的复发/难治性 DLBCL 患者仍未获得缓解。因此，研究影响CAR-T治疗DLBCL有效性的新分子预后指标并开发新的联合疗法至关重要。 回顾性收集了上海地区接受CD19 CAR-T（Axi-cel或Relma-cel）的73例DLBCL患者的数据同济大学同济医院、浙江大学医学院附属第二医院、宁波大学附属人民医院。在CD19 CAR-T细胞输注之前，患者接受了氟达拉滨和环磷酰胺化疗方案。我们的研究显示，复发/难治性弥漫性大B细胞淋巴瘤（r/r DLBCL）患者同时具有双表达（MYC > 40%和BCL2 > 50%）和 TP53 改变在 CAR-T 治疗后往往临床预后较差，即使 CAR-T 治疗与其他疗法联合使用也是如此。然而，CAR-T 疗法被发现对仅具有 TP53 改变或 DE 状态的患者有效，这表明他们的预后与没有 TP53 改变或 DE 状态的患者的预后一致。我们的研究表明，患有两种疾病的 r/r DLBCL 患者使用 CAR-T 疗法治疗的 DE 状态和 TP53 改变更有可能具有较差的临床预后。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，使其与没有这些异常的患者的预后相似。版权所有 © 2024。由 Elsevier Inc. 出版。

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.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.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.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.Copyright © 2024. Published by Elsevier Inc.