[循环肿瘤DNA监测在接受嵌合抗原受体T细胞治疗的弥漫性大B细胞淋巴瘤患者基因突变检测中的可行性及预后价值分析]
[Analysis of the feasibility and prognostic value of circulating tumor DNA monitoring in detecting gene mutations in patients with diffuse large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy].
作者信息
Zhou L H, Feng Y Q, Hu Y X, Huang H
机构信息
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine; Liangzhu Laboratory, Zhejiang University Medical Center; Institute of Hematology, Zhejiang University; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310003, China.
出版信息
Zhonghua Xue Ye Xue Za Zhi. 2023 Oct 14;44(10):805-812. doi: 10.3760/cma.j.issn.0253-2727.2023.10.003.
To explore the prognostic value of circulating tumor DNA (ctDNA) testing in patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) undergoing chimeric antigen receptor T-cell (CAR-T) therapy, and to guide the prevention and subsequent treatment of CAR-T-cell therapy failure. In this study, 48 patients with R/R DLBCL who received CAR-T-cell therapy at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2017 and March 2022 were included. Furthermore, ctDNA testing of 187 lymphoma-related gene sets was performed on peripheral blood samples obtained before treatment. The patients were divided into complete remission and noncomplete remission groups. The chi-square test and -test were used to compare group differences, and the Log-rank test was used to compare the differences in survival. Among the patients who did not achieve complete remission after CAR-T-cell therapy for R/R DLBCL, the top ten genes with the highest mutation frequencies were TP53 (41%), TTN (36%), BCR (27%), KMT2D (27%), IGLL5 (23%), KMT2C (23%), MYD88 (23%), BTG2 (18%), MUC16 (18%), and SGK1 (18%). Kaplan-Meier survival analysis revealed that patients with ctDNA mutation genes >10 had poorer overall survival (OS) rate (1-year OS rate: 0 73.8%, <0.001) and progression-free survival (PFS) rate (1-year PFS rate: 0 51.8%, =0.011) compared with patients with ctDNA mutation genes ≤10. Moreover, patients with MUC16 mutation positivity before treatment had better OS (2-year OS rate: 56.8% 26.7%, =0.046), whereas patients with BTG2 mutation positivity had poorer OS (1-year OS rate: 0 72.5%, =0.005) . ctDNA detection can serve as a tool for evaluating the efficacy of CAR-T-cell therapy in patients with R/R DLBCL. The pretreatment gene mutation burden, mutations in MUC16 and BTG2 have potential prognostic value.
探讨循环肿瘤DNA（ctDNA）检测在接受嵌合抗原受体T细胞（CAR-T）治疗的难治性/复发性弥漫性大B细胞淋巴瘤（R/R DLBCL）患者中的预后价值，并指导CAR-T细胞治疗失败的预防及后续治疗。本研究纳入了2017年12月至2022年3月期间在浙江大学医学院附属第一医院接受CAR-T细胞治疗的48例R/R DLBCL患者。此外，对治疗前采集的外周血样本进行了187个淋巴瘤相关基因集的ctDNA检测。将患者分为完全缓解组和未完全缓解组。采用卡方检验和t检验比较组间差异，采用Log-rank检验比较生存差异。在R/R DLBCL患者接受CAR-T细胞治疗后未达到完全缓解的患者中，突变频率最高的前十位基因分别为TP53（41%）、TTN（36%）、BCR（27%）、KMT2D（27%）、IGLL5（23%）、KMT2C（23%）、MYD8（p23%）、BTG2（18%）、MUC16（18%）和SGK1（18%）。Kaplan-Meier生存分析显示，ctDNA突变基因>10的患者总生存（OS）率较差（1年OS率：0 73.8%，<0.001），无进展生存（PFS）率也较差（1年PFS率：0 51.8%，=0.011），而ctDNA突变基因≤10的患者则相反。此外，治疗前MUC16突变阳性的患者OS较好（2年OS率：56.8% 26.7%，=0.046），而BTG2突变阳性的患者OS较差（1年OS率：0 72.5%，=0.005）。ctDNA检测可作为评估R/R DLBCL患者CAR-T细胞治疗疗效的工具。治疗前基因突变负荷、MUC16和BTG2突变具有潜在的预后价值。
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