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复发/难治性弥漫大 B 细胞淋巴瘤患者 CAR-T 细胞治疗后来那度胺维持治疗带来的总生存期获益

英文原题:Overall survival benefits provided by lenalidomide maintenance after chimeric antigen receptor T cell therapy in patients with refractory/relapsed diffuse large B-cell lymphoma.

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Overall survival benefits provided by lenalidomide maintenance after chimeric antigen receptor T cell therapy in patients with refractory/relapsed diffuse large B-cell lymphoma.

PubMed 2022/03/01(内容时间) Ann Transl Med

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研究概要

来那度胺维持治疗是 R/R DLBCL 患者 CAR-T 治疗后的安全有效选择。我们证实来那度胺维持治疗可改善患者的 OS,而 CAR-T 细胞耗竭的延迟可能有助于这一 OS 获益。

研究思路结论见上方概要

CAR-T 细胞疗法在难治/复发性(R/R)弥漫大B细胞淋巴瘤(DLBCL)中取得了显著疗效。然而,许多接受CAR-T 疗法的患者仍最终因靶抗原丢失或CAR-T 细胞耗竭而死于疾病复发或进展。因此,维持CAR-T 疗效已成为一个特别的研究焦点。由于来那度胺可以调节T细胞功能,我们开展了一项研究,以评估R/R DLBCL患者CAR-T 疗法后来那度胺维持治疗的疗效。

纳入7例接受CAR-T 治疗后接受来那度胺维持治疗的R/R DLBCL患者和9例单独接受CAR-T 治疗的DLBCL患者。收集所有受试者的临床数据,以评估来那度胺维持治疗的疗效。为了解来那度胺在CAR-T 治疗中可能的作用机制,通过定量实时聚合酶链反应定期检测外周血CAR-T 拷贝数,并进行了体外试验。

来那度胺维持治疗组的总生存期(OS)显著延长。此外,1例最初对CAR-T 治疗有反应但不久后复发的患者,在来那度胺暴露后再次达到完全缓解,且检测到的CAR-T 拷贝数增加。体外试验显示,来那度胺可延缓CAR-T 细胞的耗竭。

展开英文摘要原文

Chimeric antigen receptor T cell (CAR-T) therapy has achieved remarkable effects in refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL). However, many patients receiving CAR-T therapy still eventually die of disease recurrence or progression due to target antigen loss or exhaustion of CAR-T cells. Therefore, maintaining the efficacy of CAR-T has become a particular research focus. As lenalidomide can regulate T cell function, we conducted a study to evaluate the efficacy of lenalidomide maintenance after CAR-T therapy in R/R DLBCL patients.

Seven R/R DLBCL patients who received lenalidomide maintenance after CAR-T therapy and nine DLBCL patients that underwent CAR-T treatment alone were included. The clinical data of all subjects were collected to evaluate the efficacy of lenalidomide maintenance. In order to understand the possible mechanisms of lenalidomide in CAR-T therapy, CAR-T copies of peripheral blood were regularly detected by quantitative real-time polymerase chain reaction, and an in vitro test was also conducted.

Overall survival (OS) was significantly prolonged in the lenalidomide maintenance group. Furthermore, one case responding to CAR-T therapy initially but suffering a relapse shortly achieved complete remission again after lenalidomide exposure, with an increase in the number of CAR-T copies detected. The in vitro test showed that lenalidomide could delay the exhaustion of CAR-T cells.

Lenalidomide maintenance after CAR-T therapy is a safe and effective choice for R/R DLBCL patients. We confirmed that lenalidomide maintenance can improve patients' OS, and the delayed exhaustion of CAR-T cells may contribute to this OS benefit.

论文信息

作者
Ping N、Qu C、Li M、Kang L、Kong D、Chen X、Wu Q、Xia F
单位
Department of Hematology, the First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou, China.China
期刊
Annals of translational medicine2022 Mar
原文标识
PubMed 35433994 · DOI 10.21037/atm-22-20