Exploration of Targeted Anti-tumor Therapy (May 2025)

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

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

DOI
https://doi.org/10.37349/etat.2025.1002318
Journal volume & issue
Vol. 6
p. 1002318

Abstract

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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 (TP53), CD58, beta-2-microglobulin (B2M), and exportin 1 (XPO1) genes; short tandem repeats at 6p21.3 [major histocompatibility complex (MHC) class I/II], 9p24.1 (PD-L1/PD-L2), 16p13.13 [class II, MHC, transactivator gene (CIITA)]), and cytogenetic profiles [myelocytomatosis oncogene (MYC)/8q24, B-cell lymphoma 2 (BCL2)/18q21, BCL6/3q27, 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; P = 0.018). This study identified that adverse prognostic factors for PMBCL include allelic imbalance at specific loci 6p21.3 (MHC class I/II), 9p24.1 (PD-L1/PD-L2), and 16p13.13 (CIITA). 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.

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