Optimization of the First-Line Therapy in Primary Mediastinal (Thymic) Large B-Cell Lymphoma

Leonid Aleksandrovich Kramynin, L.V. Filatova, I.S. Zyuzgin, M.S. Motalkina, Yu.A. Nikulina, S.S. Elkhova, A.G. Kolgotina, I.V. Ishmatova, A.A. Zverkova, S.A. Volchenkov, E.V. Dobrovolskaya, N.S. Kolupaev, A.O. Eliseeva, E.N. Kodrul, L.А. Belyakova, T.Yu. Semiglazova,

DOI:

https://doi.org/10.21320/2500-2139-2026-19-4-408-418

BACKGROUND. The standard first-line therapies for primary mediastinal (thymic) large B-cell lymphoma (PMBCL) have not yet been clearly defined. This is a rare disease (2–4 % among all NHLs), which makes it challenging to enroll patients into large randomized studies. Most commonly, induction therapy with DA-EPOCH-R and R-CHOP regimens is used, however, no explicit advantage of one of them over the other was demonstrated by any clinical study. The role of radiotherapy (RT) in the treatment of newly diagnosed PMBCL also remains a subject to debate. Besides, there are alternative options which have proven to be effective by smaller retrospective studies, in particular, consolidation of antitumor response by high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT).

AIM. To evaluate the outcomes of the first-line therapy with the standard DA-EPOCH-R and R-CHOP regimens as well as to study the feasibility of consolidating the achieved antitumor response by means of RT or HDCT with auto-HSCT in patents with newly diagnosed PMBCL in a real-world setting at one medical institution.

MATERIALS & METHODS. This single-center cohort retrospective study enrolled 180 patients treated at the NN Petrov National Medical Cancer Research Center from 2013 to 2023. Most patients (n = 159) received therapy with DA-EPOCH-R regimen, R-CHOP was administered to fewer patients (n = 21). After achieving complete (CR) or partial response (PR) resulting from 6 drug therapy cycles and documented by PET/CT, patients either continued to be followed-up (n = 52) or received HDCT consolidation with auto-HSCT (n = 13) or RT (n = 64). The decision-making about the consolidation regimen was arbitrary, on researcher’s opinion. HDCT with auto-HSCT was most commonly administered to patients with stage III/IV and high IPI; RT was commonly used in patients with PR when the biopsy of the residual lesion with increased FDG uptake was technically impossible.

RESULTS. In the total group, overall response rate was 76.7 % (138/180): CR 59.5 % and PR 17.2 %; in 23.3 % of cases primary refractoriness of the disease was reported. With the median follow-up of 29 months (range 17–56 months), progression-free survival (PFS) was 70.0 % and overall survival (OS) was 86.1 %. By univariate analysis of long-term outcomes, neither consolidation nor the lack of it affected PFS, which accounted for 92.3 % (HDCT with auto-HSCT), 95.3 % (RT), and 90.4 % (follow-up), respectively (p = 0.29). The evaluation of OS with and without consolidation yielded significant differences: 84.6 %, 96.9 %, and 96,2 %, respectively (p = 0.023), however, the multivariate analysis proved these data to be not significant (p = 0.06).

CONCLUSION. The results of this study demonstrate the efficacy of DA-EPOCH-R regimen for PMBCL patients. After achieving CR or PR, often morphologically negative antitumor response, resulting from 6 DA-EPOCH-R cycles, the consolidation of the effect by means of RT or HDCT with auto-HSCT does not improve long-term survival rates.

  1. NCCN Guidelines Version 3.2025. Primary Mediastinal Large B-Cell Lymphoma. Available from: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf (accessed 11.03.2026).
  2. Martelli M, Ferreri A, Di Rocco A, et al. Primary mediastinal large B-cell lymphoma. Crit Rev Oncol Hematol. 2017;113:318–27. doi: 10.1016/j.critrevonc.2017.01.009. DOI: https://doi.org/10.1016/j.critrevonc.2017.01.009
  3. Piperidou A, Angelopoulou MK, Chatzidimitriou C, et al. Optimally Delivered R-da-EPOCH Versus R-CHOP-21 in Primary Mediastinal Large B-Cell Lymphoma: A Real-Life Comparison in a Single Academic Center. Cancers (Basel). 2025;17(10):1699. doi: 10.3390/cancers17101699. DOI: https://doi.org/10.3390/cancers17101699
  4. Messmer M, Tsai HL, Varadhan R, et al. R-CHOP without radiation in frontline management of primary mediastinal B-cell lymphoma. Leuk Lymphoma. 2019;60(5):1261–5. doi: 10.1080/10428194.2018.1519812. DOI: https://doi.org/10.1080/10428194.2018.1519812
  5. Held G, Thurner L, Poeschel V, et al. Role of radiotherapy and dose-densification of R-CHOP in primary mediastinal B-cell lymphoma: A subgroup analysis of the unfolder trial of the German Lymphoma Alliance (GLA). J Clin Oncol 2020;38(15_suppl);8041. doi: 10.1200/JCO.2020.38.15_suppl.8041. DOI: https://doi.org/10.1200/JCO.2020.38.15_suppl.8041
  6. Dunleavy K, Pittaluga S, Maeda LS, et al. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013;368(15):1408–16. doi: 10.1056/NEJMoa1214561. DOI: https://doi.org/10.1056/NEJMoa1214561
  7. Агрессивные нефолликулярные лимфомы — диффузная В-клеточная крупноклеточная лимфома, В-клеточная лимфома высокой степени злокачественности с перестройкой генов c-MYC и BCL2/BCL6, первичная медиастинальная В-клеточная лимфома, медиастинальная лимфома серой зоны, лимфома Беркитта, плазмобластная лимфома. Клинические рекомендации. Национальное гематологическое общество, Российское общество онкогематологов, Ассоциация онкологов России, Национальное общество детских гематологов, онкологов, 2024. (электронный документ) Доступно по: https://cr.minzdrav.gov.ru/preview-cr/129_3. Ссылка активна на 30.04.2026. [Aggressive non-follicular lymphomas: diffuse large B-cell lymphoma, B-cell high-grade lymphoma with c-MYC и BCL2/BCL6 gene rearrangement, primary mediastinal B-cell lymphoma, mediastinal grey zone lymphoma, Burkitt lymphoma, plasmablastic lymphoma. Clinical Guidelines. National Society of Hematologists, Russian Society of Oncohematologists, Russian Oncology Association, National Society of Pediatric Hematologists and Oncologists, 2024. (Internet) Available from https://cr.minzdrav.gov.ru/preview-cr/129_3. Accessed 30.04.2026. (In Russ)]
  8. Chan EHL, Koh LP, Lee J, et al. Real world experience of R-CHOP with or without consolidative radiotherapy vs DA-EPOCH-R in the first-line treatment of primary mediastinal B-cell lymphoma. Cancer Med. 2019;8(10):4626–32. doi: 10.1002/cam4.2347. DOI: https://doi.org/10.1002/cam4.2347
  9. Shah NN, Szabo A, Huntington SF, et al. R-CHOP versus dose-adjusted R-EPOCH in frontline management of primary mediastinal B-cell lymphoma: a multi-centre analysis. Br J Haematol. 2018 Feb;180(4):534–44. doi: 10.1111/bjh.15051. DOI: https://doi.org/10.1111/bjh.15051
  10. Goldschmidt N, Kleinstern G, Orevi M, et al. Favorable outcome of primary mediastinal large B-cell lymphoma patients treated with sequential RCHOP-RICE regimen without radiotherapy. Cancer Chemother Pharmacol. 2016;77(5):1053–60. doi: 10.1007/s00280-016-3024-8. DOI: https://doi.org/10.1007/s00280-016-3024-8
  11. Morgenstern Y, Aumann S, Goldschmidt N, et al. Dose-adjusted EPOCH-R is not superior to sequential R-CHOP/R-ICE as a frontline treatment for newly diagnosed primary mediastinal B-cell lymphoma: Results of a bi-center retrospective study. Cancer Med. 2021;10(24):8866–75. doi: 10.1002/cam4.4387. DOI: https://doi.org/10.1002/cam4.4387
  12. Held G, Thurner L, Poeschel V, et al. Radiation and Dose-densification of R-CHOP in Primary Mediastinal B-cell Lymphoma: Subgroup Analysis of the UNFOLDER Trial. Hemasphere. 2023;7(7):e917. doi: 10.1097/HS9.0000000000000917. DOI: https://doi.org/10.1097/HS9.0000000000000917
  13. Martelli M, Ceriani L, Ciccone G, et al. Omission of Radiotherapy in Primary Mediastinal B-Cell Lymphoma: IELSG37 Trial Results. J Clin Oncol. 2024;42(34):4071–83. doi: 10.1200/JCO-24-01373. DOI: https://doi.org/10.1200/JCO-24-01373
  14. Liu X, Deng T, Guo X, et al. A retrospective analysis of outcomes for primary mediastinal large B-cell lymphoma treated with RCHOP followed by radiotherapy or front-line autologous stem cell transplantation. Hematology. 2017;22(5):258–64. doi: 10.1080/10245332.2016.1258846. DOI: https://doi.org/10.1080/10245332.2016.1258846
  15. Avivi I, Boumendil A, Finel H, et al. Autologous stem cell transplantation for primary mediastinal B-cell lymphoma: long-term outcome and role of post-transplant radiotherapy. A report of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2018;53(8):1001–9. doi: 10.1038/s41409-017-0063-7. DOI: https://doi.org/10.1038/s41409-017-0063-7
  16. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–68. doi: 10.1200/JCO.2013.54.8800. DOI: https://doi.org/10.1200/JCO.2013.54.8800
  17. Johnson PWM, Davies AJ. Primary mediastinal B-cell lymphoma. Hematol Am Soc Hematol Educ Program. 2008;2008(1):349–58. doi: 10.1182/asheducation-2008.1.349. DOI: https://doi.org/10.1182/asheducation-2008.1.349
  18. Мангасарова Я.К., Абдурашидова Р.Р., Магомедова А.У. и др. Ответ-адаптированная стратегия терапии первичной медиастинальной В-крупноклеточной лимфомы: результаты проспективного одноцентрового клинического исследования. Клиническая онкогематология. 2024;17(4):335–46. doi: 10.21320/2500-2139-2024-17-4-335-346. [Mangasarova Ya.K., Abdurashidova R.R., Magomedova A.U., et al. Response-Adapted Strategy in the Treatment of Primary Mediastinal Large B-Cell Lymphoma: Results of a Prospective Single-Center Clinical Trial. Clinical oncohematology. 2024;17(4):335–46. doi: 10.21320/2500-2139-2024-17-4-335-346. (In Russ)] DOI: https://doi.org/10.21320/2500-2139-2024-17-4-335-346
  19. Cook MR, Williams LS, Dorris CS, et al. Improved survival for dose-intensive chemotherapy in primary mediastinal B-cell lymphoma: a systematic review and meta-analysis of 4,068 patients. Haematologica. 2024;109(3):846–56. doi: 10.3324/haematol.2023.283446. DOI: https://doi.org/10.3324/haematol.2023.283446
  20. Giulino-Roth L, O’Donohue T, Chen Z, et al. Outcomes of adults and children with primary mediastinal B-cell lymphoma treated with dose-adjusted EPOCH-R. Br J Haematol. 2017;179(5):739–47. doi: 10.1111/bjh.14951. DOI: https://doi.org/10.1111/bjh.14951
  21. Pinnix CC, Ng AK, Dabaja BS, et al. Positron emission tomography-computed tomography predictors of progression after DA-R-EPOCH for PMBCL. Blood Adv. 2018;2(11):1334–43. doi: 10.1182/bloodadvances.2018017681. DOI: https://doi.org/10.1182/bloodadvances.2018017681
  22. Melani C, Advani R, Roschewski M, et al. End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R: a paradigm shift in clinical decision making. Haematologica. 2018;103(8):1337–44. doi: 10.3324/haematol.2018.192492. DOI: https://doi.org/10.3324/haematol.2018.192492
  23. Hoppe BS, Advani R, Milgrom SA, et al. Primary mediastinal B cell lymphoma in the positron‐emission tomography era executive summary of the American Radium Society appropriate use criteria. Int J Radiat Oncol Biol Phys. 2021;111(1):36–4. doi: 10.1016/j.ijrobp.2021.03.035. DOI: https://doi.org/10.1016/j.ijrobp.2021.03.035
  24. Zinzani PL, Santoro A, Gritti G, et al. Nivolumab Combined With Brentuximab Vedotin for Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma: Efficacy and Safety From the Phase II CheckMate 436 Study. J Clin Oncol. 2019;37(33):3081–9. doi: 10.1200/JCO.19.01492. DOI: https://doi.org/10.1200/JCO.19.01492

Keywords:

primary mediastinal (thymic) large B-cell lymphoma, DA-EPOCH-R, R-CHOP, HDCT with auto-HSCT, radiotherapy

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  • Leonid Aleksandrovich Kramynin,  , NN Petrov National Medical Cancer Research Center, 68 Leningradskaya ul., pos. Pesochnyi, Saint Petersburg, Russian Federation, 197758, e-mail: kramleo@yandex.ru

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Published

01.10.2026

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Vol. 19 No. 4 (2026)
LYMPHOID TUMORS

How to Cite

Kramynin L.A., Filatova L.V., Zyuzgin I.S., et al. Optimization of the First-Line Therapy in Primary Mediastinal (Thymic) Large B-Cell Lymphoma. Clinical Oncohematology. Basic Research and Clinical Practice. 2026;19(4):408–418. doi:10.21320/2500-2139-2026-19-4-408-418.

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