弥漫性大B细胞淋巴瘤患者中免疫球蛋白重链重排和免疫球蛋白κ轻链重排的预后相关性

Prognostic relevance of immunoglobulin heavy chain rearrangement and immunoglobulin kappa light chain rearrangement in patients with diffuse large B cell lymphoma.

作者信息

Wang Jie, Zhao Sha, Niu Ting, Chen Jie, Li He, Xiong Hui, Ke Zhonghe, Xin Beibei, Zhu Kexin, Tang Yuan

机构信息

Department of Hematology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.

Department of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.

出版信息

Oncologist. 2025 Mar 10;30(3). doi: 10.1093/oncolo/oyaf016.

DOI:10.1093/oncolo/oyaf016

PMID:40063611

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11892554/

Abstract

PURPOSES

Evidence has demonstrated that monitoring of the variable, diversity, and joining gene segments (VDJ) rearrangement of immunoglobulin (Ig) gene in the circulating tumor DNA (ctDNA) is highly valuable in predicting the prognosis of patients with diffuse large B cell lymphoma (DLBCL). In this study, we investigated the role of both Ig heavy chain (IGH) and Ig kappa light chain (IGK) gene rearrangements detected in ctDNA samples in predicting DLBCL progression.

METHODS

Next-generation sequencing (NGS) was used to identify the dominant V(D)J clonotypic rearrangement in tissue samples of 33 DLBCL patients. Minimal residual disease (MRD) was monitored at the interim and end of the treatment, as well as the follow-up time by tracking the dominant V(D)J clonotypic rearrangement (defined as the "NGS MRD" method) in the peripheral blood (PB) ctDNA samples. The nomogram was established to predict the 12-month and 24-month progression-free survival (PFS) probability.

RESULTS

Prior to treatment, the dominant clones identified in the tissue samples could be retrieved in tissue-matched PB of 26 (78.8%, 26/33) patients. The addition of IGK clones to IGH clones increased the MRD detection rate from 42.9% to 58.0% in the total series. NGS MRD and imaging scans showed poor concordance at the interim of treatment (Kappa = 0.24) and the follow-up time (Kappa = 0.28), and fair concordance at the end of treatment (Kappa = 0.46). However, we confirmed that the interim NGS MRD monitoring demonstrated improved prognostic performance compared to imaging scans, and both NGS MRD monitoring and imaging scans served as valuable prognostic factors for PFS at the end of treatment. Notably, NGS MRD monitoring predicted disease relapse in 3 patients prior to imaging scans. Furthermore, we found that both the faster IGH and IGK clone clearance rates were associated with favorable prognosis. The nomogram model identified IGH and IGK clone clearance rates, together with the interim NGS MRD result were the important predictors of 12-month and 24-month progression of DLBCL.

CONCLUSIONS

MRD monitoring via NGS of Ig for both IGH and IGK is a promising noninvasive tool for prognosis prediction and early relapse prediction of DLBCL patients.

摘要

目的

有证据表明，监测循环肿瘤DNA（ctDNA）中免疫球蛋白（Ig）基因的可变区、多样性区和连接区基因片段（VDJ）重排，对于预测弥漫性大B细胞淋巴瘤（DLBCL）患者的预后具有很高的价值。在本研究中，我们调查了在ctDNA样本中检测到的Ig重链（IGH）和Igκ轻链（IGK）基因重排在预测DLBCL进展中的作用。

方法

采用二代测序（NGS）鉴定33例DLBCL患者组织样本中的主要V（D）J克隆型重排。通过追踪外周血（PB）ctDNA样本中的主要V（D）J克隆型重排（定义为“NGS MRD”方法），在治疗中期、末期以及随访期间监测微小残留病（MRD）情况。建立列线图以预测12个月和24个月的无进展生存（PFS）概率。

结果

治疗前，在26例（78.8%，26/33）患者与组织匹配的PB中可检索到组织样本中鉴定出的主要克隆。在整个队列中，将IGK克隆添加到IGH克隆中可使MRD检测率从42.9%提高到58.0%。NGS MRD与影像学扫描在治疗中期（Kappa = 0.24）和随访期间（Kappa = 0.28）一致性较差，在治疗末期一致性尚可（Kappa = 0.46）。然而，我们证实，与影像学扫描相比，中期NGS MRD监测显示出更好的预后性能，并且NGS MRD监测和影像学扫描均是治疗末期PFS的重要预后因素。值得注意的是，NGS MRD监测在影像学扫描前预测了3例患者的疾病复发。此外，我们发现IGH和IGK克隆清除率较快均与良好预后相关。列线图模型确定IGH和IGK克隆清除率以及中期NGS MRD结果是DLBCL 12个月和24个月进展的重要预测因素。