Vol. 17 No. 3 (2024), LYMPHOID TUMORS
Vol. 17 No. 3 (2024)
LYMPHOID TUMORS

Treatment Outcomes in Primary Mediastinal Large B-Cell Lymphoma. Experience of the AF Tsyb Medical Radiological Research Center (Obninsk)

Published 01.07.2024
Alena Yurevna Terekhova
AF Tsyb Medical Radiological Research Center, branch of the NMRC of Radiology, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036
https://orcid.org/0000-0002-7458-0269
N.A. Falaleeva
AF Tsyb Medical Radiological Research Center, branch of the NMRC of Radiology, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036
https://orcid.org/0000-0002-0023-4216
A.B. Galitsyna
MIFI National Research Nuclear University, Obninsk Institute for Nuclear Power Engineering, 1 Studgorodok ter., Obninsk, Kaluga Region, Russian Federation, 249040
https://orcid.org/0009-0009-0188-8420
A.M. Chelmakov
AF Tsyb Medical Radiological Research Center, branch of the NMRC of Radiology, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036
https://orcid.org/0009-0001-0236-1390
A.A. Vovchenko
AF Tsyb Medical Radiological Research Center, branch of the NMRC of Radiology, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036
https://orcid.org/0009-0009-6911-3322
N.A. Riabikina
AF Tsyb Medical Radiological Research Center, branch of the NMRC of Radiology, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036
https://orcid.org/0009-0000-2769-0601
A.A. Danilenko
AF Tsyb Medical Radiological Research Center, branch of the NMRC of Radiology, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036
https://orcid.org/0000-0002-6798-6076
T. I. Bogatyreva
AF Tsyb Medical Radiological Research Center, branch of the NMRC of Radiology, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036
https://orcid.org/0000-0003-1753-9232
2024-3
PDF_2024-17-3_225-236 (Russian)

Keywords

primary mediastinal large B-cell lymphoma
immunochemotherapy
radiotherapy
immediate and long-term treatment outcomes
PET-CT

How to Cite

1.
Terekhova A.Y., Falaleeva N.A., Galitsyna A.B., et al. Treatment Outcomes in Primary Mediastinal Large B-Cell Lymphoma. Experience of the AF Tsyb Medical Radiological Research Center (Obninsk). Клиническая онкогематология. 2024;17(3):225-236. doi:10.21320/2500-2139-2024-17-3-225-236
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Abstract

AIM. To assess chemotherapy outcomes in patients with primary mediastinal large B-cell lymphoma (PMBCL) treated at the AF Tsyb Medical Radiological Research Center from 2016 to 2023.

MATERIALS & METHODS. The analysis focused on the data from 58 patients with the morphologically verified diagnosis of PMBCL. The patients were aged 17–62 years (median 34 years), there were 39 women and 19 men. The median follow-up was 51.2 months (range 0.4–200.9 months). Depending on drug chemotherapy regimens, patients were divided into 3 groups: R-NHL-BFM-90 (n = 9), R-CHOP (n = 17), and R-MACOP-B (n = 32). Most patients (90 %) received mediastinal radiotherapy of total 30–46 Gy.

RESULTS. The 5-year overall survival in the therapy groups was 66.7 %, 88.2 %, and 100 %, respectively (p = 0.007), progression-free survival was 66.7 %, 70.6 %, and 96.9 % (p = 0.006), and event-free survival was 66.7 %, 54.7 %, and 90.6 % (p = 0.038). On the whole, the toxicity profile of chemotherapy was quite acceptable. Neither low blood values nor other adverse events essentially affected a complete implementation of chemoradiotherapy program. The intermediate outcomes were based on PET-CT data after 2–4 therapy cycles in 37 (64 %) patients. PET-CT showed that at the stage of drug chemotherapy, complete response (CR) was achieved in 27 (73 %) patients, and partial response (PR) was achieved in 4 (11 %) patients. With respect to the CR and PR criteria, there were 6 (16 %) non-responders.

CONCLUSION. PMBCL is one of extranodal lymphomas with thymic B-cells being primary source of tumor growth. PMBCL is characterized by aggressive course and extreme heterogeneity of clinical manifestations. Up to now, the first-line chemotherapy decision making in PMBCL has remained an issue with practical importance. This paper reports immediate and long-term outcomes of the program chemoradiotherapy regimen R-MACOP-B with subsequent consolidation radiotherapy. The results obtained can be termed quite satisfactory and noninferior to the data from national and international sources. Nevertheless, more effective chemoradiotherapy programs for PMBCL continue to be elaborated. In this context, immune checkpoint inhibitors as part of therapy programs seem to hold promise for the treatment of newly diagnosed PMBCL.

PDF_2024-17-3_225-236 (Russian)

References

  1. Barth TFE, Leithauser F, Joos S, et al. Mediastinal (thymic) large B-cell lymphoma: where do we stand? Lancet Oncol. 2002;3(4):229–34. doi: 10.1016/s1470-2045(02)00714-3.
  2. Glynn E, Soma L, Wu D, et al. Flow Cytometry for Non-Hodgkin and Hodgkin Lymphomas. Methods Mol Biol. 2019;1956:35–60. doi: 10.1007/978-1-4939-9151-8_2.
  3. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90. doi: 10.1182/blood-2016-01-643569.
  4. 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.
  5. Pfau D, Smith DA, Beck R, et al. Primary mediastinal large B-cell lymphoma: a review for radiologists. Am J Roentgenol. 2019;213(5):W194–W210. doi: 10.2214/AJR.19.21225.
  6. Fakhri B, Ai W. Current and emerging treatment options in primary mediastinal B-cell lymphoma. Ther Adv Hematol. 2021;12:20406207211048959. doi: 10.1177/20406207211048959.
  7. Noerenberg D, Briest F, Hennch C, et al. Genetic Characterization of Primary Mediastinal B-Cell Lymphoma: Pathogenesis and Patient Outcomes. J Clin Oncol. 2024;42(4):452–66. doi: 10.1200/JCO.23.01053.
  8. Tuveri S, Debackere K, Marcelis L, et al. Primary mediastinal large B-cell lymphoma is characterized by large-scale copy-neutral loss of heterozygosity. Genes Chromosomes Cancer. 2022;61(10):603–15. doi: 10.1002/gcc.23069.
  9. Aoki T, Shimada K, Suzuki R, et al. High-dose chemotherapy followed by autologous stem cell transplantation for relapsed/refractory primary mediastinal large B-cell lymphoma. Blood Cancer J. 2015;5(12):e372. doi: 10.1038/bcj.2015.101.
  10. Alkhaldi H, Reinhardt A, Barnett M, et al. High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma. Transplant Cell Ther. 2023;29(11):690–4. doi: 10.1016/j.jtct.2023.08.019.
  11. Takyar J, Raut M, Borse R, et al. Relapsed/refractory primary mediastinal large B-cell lymphoma: a structured review of epidemiology, treatment guidelines and real-world treatment practices. Expert Rev Hematol. 2020;13(3):275–87. doi: 10.1080/17474086.2020.1716725.
  12. Zinzani PL, Thieblemont C, Melnichenko V, et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: final analysis of KEYNOTE-170. Blood. 2023;142(2):141–5. doi: 10.1182/blood.2022019340.
  13. Savage KJ. Primary mediastinal large B-cell lymphoma. Blood. 2022;140(9):955–70. doi: 10.1182/blood.2020008376.
  14. Todeschini, G, Ambrosetti, A, Meneghini, V, et al. Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients. J Clin Oncol. 1990;8(5):804–8. doi: 10.1200/JCO.1990.8.5.804.
  15. Lazzarino M, Orlandi E, Paulli M, et al. Primary mediastinal B-cell lymphoma with sclerosis: an aggressive tumor with distinctive clinical and pathologic features. J Clin Oncol. 1993;11(12):2306–13. doi: 10.1200/JCO.1993.11.12.2306.
  16. De Sanctis V, Finolezzi E, Osti MF, et al. MACOP-B and involved-field radiotherapy is an effective and safe therapy for primary mediastinal large B cell lymphoma. Int J Radiat Oncol Biol Phys. 2008;72(4):1154–60. doi: 10.1016/j.ijrobp.2008.02.036.
  17. Zinzani PL, Stefoni V, Finolezzi E, et al. Rituximab combined with MACOP-B or VACOP-B and radiation therapy in primary mediastinal large B-cell lymphoma: a retrospective study. Clin Lymphoma Myeloma. 2009;9(5):381–5. doi: 10.3816/CLM.2009.n.074.
  18. Zinzani PL, Martelli M, Magagnoli M, et al. Treatment and clinical management of primary mediastinal large B-cell lymphoma with sclerosis: MACOP-B regimen and mediastinal radiotherapy monitored by (67) gallium scan in 50 patients. Blood. 1999;94(10):3289–93.
  19. Zinzani PL, Martelli M, Bendandi M, et al. Primary mediastinal large B-cell lymphoma with slerosis: a Clinical study of 89 patients treated with MACOP-B chemotherapy and radiation therapy. Haematologica. 2001;86(2):187–91.
  20. Todeschini G, Secchi S, Morra E, et al. Primary mediastinal large B-cell lymphoma (PMLBCL): long-term results from a retrospective multicentre Italian experience in 138 patients treated with CHOP or MACOP-B/VACOP-B. Br J Cancer 2004;90(2):372–6. doi: 10.1038/sj.bjc.6601460.
  21. Zinzani PL, Broccoli A, Casadei B, et al. The role of rituximab and positron emission tomography in the treatment of primary mediastinal large B-cell lymphoma: experience on 74 patients. Hematol Oncol. 2015;33(4):145–50. doi: 10.1002/hon.2172.
  22. Broccoli A, Casadei B, Stefoni V, et al. The treatment of primary mediastinal large B-cell lymphoma: a two decades monocentric experience with 98 patients. BMC Cancer. 2017;17(1):276. doi: 10.1186/s12885-017-3269-6.
  23. Vassilakopoulos TP, Pangalis GA, Katsigiannis A, et al. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone with or without radiotherapy in primary mediastinal large B-cell lymphoma: the emerging standard of care. Oncologist. 2012;17(2):239–49. doi: 10.1634/theoncologist.2011-0275.
  24. Rieger M, Osterborg A, Pettengell R, et al. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol. 2011;22(3):664–70. doi: 10.1093/annonc/mdq418.
  25. Soumerai JD, Hellmann MD, Feng Y, et al. Treatment of primary mediastinal B-cell lymphoma with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone is associated with a high rate of primary refractory disease. Leuk Lymphoma. 2014;55(3):538–43. doi: 10.3109/10428194.2013.810738.
  26. Fietz T, Knauf WU, Hanel M, et al. Treatment of primary mediastinal large B cell lymphoma with an alternating chemotherapy regimen based on high-dose methotrexate. Ann Hematol. 2009;88(5):433–9. doi: 10.1007/s00277-008- 0625–2.
  27. Pohlen M, Gerth HU, Liersch R, et al. Efficacy and toxicity of a rituximab and methotrexate based regimen (GMALL B-ALL/NHL 2002 protocol) in Burkitt’s and primary mediastinal large B-cell lymphoma. Am J Hematol. 2011;86(12):61–76. doi: 10.1002/ajh.22165.
  28. Wehde N, Borte G, Liebmann A, et al. Primary mediastinal large B cell lymphoma: Frontline treatment with an alternating chemotherapy regimen based on high dose methotrexate – A single institution experience. J Med Soc. 2017;31(1):8–13. doi: 10.4103/0972-4958.198427.
  29. 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.
  30. Dunleavy K, Pittaluga S, Janik J, et al. Primary mediastinal large B-cell lymphoma (PMBL) outcome may be significantly improved by the addition of rituximab to dose-adjusted (DA)-EPOCH and obviates the need for radiation: results from a prospective study of 44 patients. Blood. 2006;108:66A.
  31. 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;180(4):534–44. doi: 10.1111/bjh.15051.
  32. Malenda A, Kolkowska-Lesniak A, Pula B, et al. Outcomes of treatment with dose-adjusted EPOCH-R or R-CHOP in primary mediastinal large B-cell lymphoma. Eur J Haematol. 2020;104(1):59–66. doi: 10.1111/ejh.13337.
  33. 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.
  34. Агрессивные нефолликулярные лимфомы — диффузная крупноклеточная В-клеточная лимфома, первичная медиастинальная В-клеточная лимфома, лимфома Беркитта: Клинические рекомендации МЗ РФ, 2020 (электронный документ). Доступно по: https://oncology.ru/specialist/treatment/references/actual/129.pdf?ysclid=lveyfue9d3790543412. Ссылка активна на 25.04.2024. [Aggressive nonfollicular lymphomas: diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, Burkitt lymphoma. Clinical guidelines of the Ministry of Health of the Russian Federation (Internet). Available from: https://oncology.ru/specialist/treatment/references/actual/129.pdf?ysclid=lveyfue9d3790543412. Accessed 25.04.2024. (In Russ)]
  35. 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.
  36. 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.
  37. 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.
  38. Lees C, Keane C, Gandhi MK, Gunawardana J. Biology and therapy of primary mediastinal B-cell lymphoma: current status and future directions. Br J Haematol. 2019;185(1):25–41. doi: 10.1111/bjh.15778.
  39. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405. doi: 10.1182/blood-2016-03-643544.
  40. The International Non-Hodgkin Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993;329(14):987–94. doi: 10.1056/nejm199309303291402.
  41. Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of Imaging in the Staging and Response Assessment of Lymphoma: Consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32(27):3048–58. doi: 10.1200/jco.2013.53.5229.
  42. Мангасарова Я.К., Магомедова А.У., Кравченко С.К. и др. Восьмилетний опыт лечения агрессивных В-крупноклеточных лимфом средостения. Терапевтический архив. 2013;8(7):50–6. [Mangasarova Ya.K., Magomedova A.U., Kravchenko S.K., et al. The 8-year treatment experience with aggressive mediastinal large B-cell lymphomas. Terapevticheskii arkhiv. 2013;8(7):50–6. (In Russ)]
  43. Габеева Н.Г., Королева Д.А., Татарникова С.А. и др. Промежуточные результаты терапии первичной медиастинальной В-крупноклеточной лимфомы по протоколам «ПМЛ-16» и «ПМЛ-19». Гематология и трансфузиология. 2022;67(3):328–50. doi: 10.35754/0234-5730-2022-67-3-328-350. [Gabeeva N.G., Koroleva D.A., Tatarnikova S.A., et al. Interim results of the PML-16, PML-19 protocols for primary mediastinal large B-cell lymphoma therapy. Russian journal of hematology and transfusiology. 2022;67(3):328–50. doi: 10.35754/0234-5730-2022-67-3-328-350. (In Russ)]
  44. Davies AJ, Zucca E, Ceriani L, et al. A randomized trial of observation versus radiotherapy in primary mediastinal B-cell lymphoma patients with complete metabolic response after standard immunochemotherapy. Hematol Oncol. 2023;41(Suppl 2):48–50. doi: 10.1002/hon.3163_19.
  45. National Library of Medicine. Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma (Internet). Available from: https://clinicaltrials.gov/study/NCT04759586?titles=NSC%20№%20748726&rank=3 (accessed 15.11.2023).
  46. Prochazka V, Henzlova L, Buriankova E, et al. Prognostic Impact of Interim and Final PET in Primary Mediastinal Large B-Cell Lymphoma Treated with Intensive Etoposide-Based Therapy. Blood. 2014;124(21):1729. doi: 10.1182/blood.V124.21.1729.1729.
  47. Lazarovici J, Terroir M, Arfi-Rouche J, et al. Poor predictive value of positive interim FDG-PET/CT in primary mediastinal large B-cell lymphoma. Eur J Nucl Med Mol Imaging. 2017;44(12):2018–24. doi: 10.1007/s00259-017-3758-5.
  48. Avigdor A, Sirotkin T, Kedmi M, et al. The impact of R-VACOP-B and interim FDG-PET/CT on outcome in primary mediastinal large B cell lymphoma. Ann Hematol. 2014;93(8):1297–304. doi: 10.1007/s00277-014-2043-y.
  49. Armand P, Rodig S, Melnichenko V, et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma. J Clin Oncol. 2019;37(34):3291–9. doi: 10.1200/JCO.19.01389.
  50. 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.
  51. Zinzani PL, Pellegrini C, Chiappella A, et al. Brentuximab vedotin in relapsed primary mediastinal large B-cell lymphoma: Results from a phase 2 clinical trial. Blood. 2017;129(16):2328–30. doi: 10.1182/blood-2017-01-764258.
  52. Zinzani PL, Santoro A, Gritti G, et al. Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: a 3-year follow-up. Blood Adv. 2023;7(18):5272–80. doi: 10.1182/bloodadvances.2023010254.
  53. Huang G, Huang J, Zhang Z, et al. Nivolumab plus gemcitabine, dexamethasone, and cisplatin chemotherapy induce durable complete remission in relapsed/refractory primary mediastinal B-cell lymphoma: a case report and literature review. Int Med Res. 2020;48(8):300060520945075. doi: 10.1177/0300060520945075.
  54. De-la-Fuente C, Nunez F, Cortes-Romera M, et al. Pembrolizumab for refractory primary mediastinal B-cell lymphoma with central nervous system involvement. Hematol Oncol. 2021;39(3):419–22. doi: 10.1002/hon.2836.
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