生物标志物在原发性纵隔大B细胞淋巴瘤中的预后影响：免疫检查点抑制剂早期整合的理论依据

Prognostic impact of biomarkers in PMBCL: rationale for early integration of immune checkpoint inhibitors.

作者信息

Mangasarova Yana K, Abdurashidova Runiza R, Risinskaya Natalya V, Biderman Bella V, Abramova Tatiana V, Surin Vadim L, Shupletsova Irina A, Obukhova Tatiana N, Iusupov Rasul I, Chabaeva Yulia A, Magomedova Aminat U, Nikulina Lena E, Kulikov Sergei M, Zvonkov Eugene E, Kovrigina Alla M, Sudarikov Andrey B

机构信息

National Medical Research Center for Hematology, 125167 Moscow, Russian Federation.

Lomonosov Moscow State University, 119991 Moscow, Russian Federation.

出版信息

Explor Target Antitumor Ther. 2025 May 20;6:1002318. doi: 10.37349/etat.2025.1002318. eCollection 2025.

DOI:10.37349/etat.2025.1002318

PMID:40416849

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12098338/

Abstract

AIM

This research aims to guide future strategies for personalized treatment of primary mediastinal large B-cell lymphoma (PMBCL), particularly to identify high-risk patients who may benefit from incorporating immune checkpoint inhibitors (ICIs) in the first-line setting.

METHODS

A retrospective, single-center study included 254 newly diagnosed PMBCL patients treated with rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (R-DA-EPOCH), rituximab, modified protocol NHL-BFM-90 (RmNHL-BFM-90), or R-DA-EPOCH combined with nivolumab. Clinical parameters, immunohistochemical markers [programmed death ligand-1 (PD-L1), programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), human leucocyte antigen (HLA)-DR, Ki-67, multiple myeloma oncogene 1 (MUM1)], molecular markers (mutations in tumor protein p53 (), , beta-2-microglobulin (), and exportin 1 () genes; short tandem repeats at 6p21.3 [major histocompatibility complex () class I/II], 9p24.1 (/), 16p13.13 [class II, MHC, transactivator gene ()]), and cytogenetic profiles [myelocytomatosis oncogene ()/8q24, B-cell lymphoma 2 ()/18q21, /3q27, del17p13, and karyotype abnormalities] were analyzed.

RESULTS

The addition of nivolumab to R-DA-EPOCH as a first-line regimen significantly improved event-free survival (EFS; = 0.018). This study identified that adverse prognostic factors for PMBCL include allelic imbalance at specific loci 6p21.3 ( class I/II), 9p24.1 (/), and 16p13.13 (). Incorporating nivolumab into the R-DA-EPOCH regimen as a first-line therapy has shown potential in reducing adverse prognostic factors.

CONCLUSIONS

These findings suggest that high-risk patients may benefit significantly from the early incorporation of ICIs into their treatment plans.

摘要

目的

本研究旨在指导原发性纵隔大B细胞淋巴瘤（PMBCL）个性化治疗的未来策略，尤其是识别可能从一线治疗中加入免疫检查点抑制剂（ICI）中获益的高危患者。

方法

一项回顾性单中心研究纳入了254例新诊断的PMBCL患者，这些患者接受了利妥昔单抗、剂量调整的依托泊苷、泼尼松、长春新碱、环磷酰胺、阿霉素（R-DA-EPOCH）、利妥昔单抗、改良方案NHL-BFM-90（RmNHL-BFM-90）或R-DA-EPOCH联合纳武单抗治疗。分析了临床参数、免疫组化标志物[程序性死亡配体-1（PD-L1）、程序性死亡-1（PD-1）、细胞毒性T淋巴细胞相关蛋白4（CTLA-4）、人类白细胞抗原（HLA）-DR、Ki-67、多发性骨髓瘤癌基因1（MUM1）]、分子标志物（肿瘤蛋白p53（）、、β2微球蛋白（）和输出蛋白1（）基因的突变；6p21.3[主要组织相容性复合体（）I/II类]、9p24.1（/）、16p13.13[II类，MHC，反式激活基因（）]处的短串联重复序列）以及细胞遗传学图谱[髓细胞瘤癌基因（）/8q24、B细胞淋巴瘤2（）/18q21、/3q27、del17p13和核型异常]。

结果

作为一线方案，在R-DA-EPOCH中加入纳武单抗显著改善了无事件生存期（EFS； = 0.018）。本研究确定PMBCL的不良预后因素包括特定基因座6p21.3（I/II类）、9p24.1（/）和16p13.13（）处的等位基因失衡。作为一线治疗，将纳武单抗纳入R-DA-EPOCH方案已显示出降低不良预后因素的潜力。