Первичная медиастинальная В-клеточная лимфома: эволюция и перспективы первой линии терапии. Обзор литературы
Первичная медиастинальная В-клеточная лимфома – агрессивная неходжкинская лимфома, занимающая пограничное положение между диффузной крупноклеточной В-клеточной лимфомой и классической лимфомой Ходжкина. По причине редкой встречаемости и малого количества проспективных клинических исследований единые стандарты терапии первичной медиастинальной В-клеточной лимфомы не определены. Исход при рефрактерном или рецидивирующем течении остается крайне неблагоприятным, поэтому выбор оптимального режима первой линии терапии особенно актуален. Первая линия терапии представлена двумя основными режимами: R-CHOP и DA-EPOCH-R, доказавшими свою эффективность в ретроспективных исследованиях. С учетом агрессивного течения лимфомы более интенсивные подходы к терапии остаются наиболее предпочтительными. После индукционной терапии R-CHOP следует консолидация лучевой терапией или альтернативными режимами (R-ICE). Режим DA-EPOCH-R не требует консолидирующего облучения средостения. После окончания лекарственного лечения с целью дифференцировки остаточной опухолевой ткани от фиброзных и воспалительных изменений в средостении и определения показаний к последующей лучевой терапии выполняется ПЭТ-КТ, которая, однако, имеет большой процент ложноположительных результатов. Инициированные клинические исследования помогут определить обоснованность консолидирующей лучевой терапии после ритуксимаб-содержащих режимов при полном метаболическом ответе, целесообразность применения ПЭТ-КТ в качестве дифференциально-диагностического метода, преимущество режима DA-EPOCH или R-CHOP, а также необходимость применения иммуноконъюгатов, ингибиторов иммунных контрольных точек в комбинации со стандартной терапией с целью улучшения отдаленных результатов лечения.Крамынин Л.А., Филатова Л.В., Зюзгин И.С., Моталкина М.С., Елхова С.С., Добровольская Е.В., Ковязин А.К., Семиглазова Т.Ю.
Ключевые слова
первичная медиастинальная В-клеточная лимфома
первая линия терапии
Список литературы
1. Salama M.E., Rajan Mariappan M., Inamdar K. et al. The value of CD23 expression as an additional marker in distinguishing mediastinal (thymic) large B-cell lymphoma from Hodgkin lymphoma. Int J Surg Pathol. 2010;18:121–28. Doi: 10.1177/1066896909331994.
2. Copie-Bergman C., Plonquet A., Alonso M.A., et al. MAL expression in lymphoid cells: further evidence for MAL as a distinct molecular marker of primary mediastinal large B-cell lymphomas. Mod Pathol. 2002;15(11):1172–80. Doi: 10.1097/01.MP.0000032534.81894.B3.
3. 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.
4. Jaffe E.S., Harris N.L., Stein H., Vardiman J.W., eds. WHO Classification of Tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press, 2001.
5. Ashraf A., Abou-Elella D.D.W., Vose J.M., et al. Primary Mediastinal Large B-Cell Lymphoma: A Clinicopathologic Study of 43 Patients From the Nebraska Lymphoma Study Group. J Clin Oncol. 1999;17(3):784–90. Doi: 10.1200/JCO.1999.17.3.784.
6. Johnson P.W.M., Davies A.J. Primary mediastinal B-cell lymphoma. Hematol Am Soc Hematol Educ Program. 2008;2008(1):349–58. Doi: 10.1182/asheducation-2008.1.349.
7. Kuruvilla J., Pintilie M., Tsang R., et al. Salvage chemotherapy and autologous stem cell transplantation are inferior for relapsed or refractory primary mediastinal large B-cell lymphoma compared with diffuse large B-cell lymphoma. Leuk Lymphoma. 2008;49(7):1329–36. Doi: 10.1080/10428190802108870.
8. Abou-Elella A.A., Weisenburger D.D., Vose J.M., et al. Primary mediastinal large B-cell lymphoma: a clinicopathologic study of 43 patients from the Nebraska Lymphoma Study Group. J Clin Oncol. 1999;17(3):784–90. Doi: 10.1200/JCO.1999.17.3.784.
9. Zinzani P.L., Martelli M., Bertini M., et al. Induction chemotherapy strategies for primary mediastinal large B-cell lymphoma with sclerosis: a retrospective multinational study on 426 previously untreated patients. Haematologica. 2002;87(12):1258–64.
10. 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):372–76. Doi: 10.1038/sj.bjc.6601460.
11. Marcus R., Imrie K., Belch A. et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005;105(4):1417–23. Doi: 10.1182/blood-2004-08-3175.
12. Hiddemann W., Kneda M., Dreyling M., et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with CHOP alone: results of prospective randomized study of the German Low Grade Lymphoma Study Group. Blood. 2005;106(12):3725–32. Doi: 10.1182/blood-2005-01-0016.
13. van Oers M.H., Klasa R., Marcus R., et al. Rituximab maintenance improves clinical outcome of relapse/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase III intergroup trial. Blood. 2006;108(10):3295–301. Doi: 10.1182/blood-2006-05-021113.
14. Forstpointner R., Dreyling M. et al. The addition of rituximab to FCM significantly increase the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphoma: results of prospective randomized study of the German Low Grade Lymphoma Study Group. Blood. 2004;104(10):3064–71. Doi: 10.1182/blood-2004-04-1323.
15. Coiffier B., Lepage E., Briere J. et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B-cell lymphoma. N Engl J Med. 2002;346(4):235–42. Doi: 10.1056/NEJMoa011795.
16. Pfreundschuh M., Trumper L., Osterborg A., et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large B-cell lymphoma: a randomized controlled trial by the MabThera International Trial (MinT) Group. Lancet Oncol. 2006;7(5):379–91. Doi: 10.1016/S1470-2045(06)70664-7.
17. Habermann T., Weller E., et al. Rituximab-CHOP versus CHOP alone without or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(19):3121–27. Doi: 10.1200/JCO.2005.05.1003.
18. Lenz G., Dreyling M. et al. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of prospective randomized study of the German Low Grade Lymphoma Study Group. J Clin Oncol. 2005;23:1984–92. Doi: 10.1200/JCO.2005.08.133.
19. Heroid M., Haas A., et al. Rituximab added to first-line mitoxantrone, chlorambucil and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007;25(15):1986–92.
20. Savage K.J., Al-Rajhi N., Voss N., et al. Favorable outcome of primary mediastinal large B-cell lymphoma in a single institution: the British Columbia experience. Ann Oncol. 2006;17(1):123–30. Doi: 10.1093/annonc/mdj030.
21. Zinzani P.L., 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):381–85. Doi: 10.3816/CLM.2009.n.074.
22. 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.
23. 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.
24. Soumerai J.D., Hellmann M.D., 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.
25. Dunleavy K., Pittaluga S., Maeda L.S., 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.
26. 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.
27. Chan E.H.L., Koh L.P., 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.
28. Shah N.N., Szabo A., Huntington S.F., 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.
29. Melani C., Wilson W.H., Roschewski M. What is the standard of care for primary mediastinal b-cell lymphoma; R-CHOP or DA-EPOCH-R? Br J Haematol. 2019;184(5):836–38. Doi: 10.1111/bjh.15185.
30. Shah N.N., Fenske T.S., Hamadani M., Svoboda J. What is the standard of care for primary mediastinal B cell lymphoma; R-CHOP or DA-EPOCH-R? – Response to Melani et al. Br J Haematol. 2019;184(5):838–40. Doi: 10.1111/bjh.15183.
31. Bartlett N.L., Wilson W.H., Jung S.H., et al. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol. 2019;37(21):1790–99. Doi: 10.1200/JCO.18.01994.
32. Jackson M.W., Rusthoven C.G., Jones B.L., et al. Improved survival with combined modality therapy in the modern era for primary mediastinal B-cell lymphoma. Am J Hematol. 2016 May;91(5):476–80. Doi: 10.1002/ajh.24325.
33. Messmer M., Tsai H.L., Varadhan R., et al. R-CHOP without radiation in frontline management of primary mediastinal B-cell lymphoma. Leuk Lymphoma. 2019;60(5):1261–65. Doi: 10.1080/10428194.2018.1519812.
34. 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). 2020;38(15_suppl):8041–8041.
35. Jiang S., Zhen H., Jiang H. Role of Radiation Therapy in Younger and Older Adults with Primary Mediastinal Large B Cell Lymphoma in Rituximab Era: A U.S. Population-Based Analysis. J Adolesc Young Adult Oncol. 2019;8(5):623–27. Doi: 10.1089/jayao.2019.0018.
36. Smith G., Raj B.V., Ranjan P., et al. Role of radiation therapy in primary mediastinal large B-cell lymphoma in rituximab era: A US population-based analysis. Am J Hematol. 2015;90(11):1052–54. Doi: 10.1002/ajh.24172.
37. Schaapveld M., Aleman B.M., van Eggermond A.M., et al. Second cancer risk up to 40 years after treatment for hodgkin’s lymphoma. N Engl J Med. 2015;373:2499–511. Doi: 10.1056/NEJMoa1505949.
38. Bhakta N., Liu Q., Yeo F., et al. Cumulative burden of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin’s lymphoma: an analysis from the St Jude Lifetime Cohort Study. Lancet Oncol. 2016;17:1325–34. Doi: 10.1016/S1470-2045(16)30215-7.
39. Giulino‐Roth L. How I treat primary mediastinal B‐cell lymphoma. Blood. 2018;132(8):782–90.
40. Hayden A.R., Tonseth P., Lee D.G., Villa D., Gerrie A.S., Scott D.W., et al. Outcome of primary mediastinal large B‐cell lymphoma using R‐CHOP: impact of a PET‐adapted approach. Blood. 2020;136(24):2803–11. Doi: 10.1182/blood.2019004296.
41. Hoppe B.S., Advani R., Milgrom S.A., 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.
42. Pinnix C.C., Ng A.K., Dabaja B.S., et al. Positron emission tomography-computed tomography predictors of progression after DA-R-EPOCH for PMBCL. Blood Adv. 2018;2(11):1334-1343. doi: 10.1182/bloodadvances.2018017681
43. 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 Aug;103(8):1337–44. Doi: 10.3324/haematol.2018.192492.
44. Filippi A.R., Piva C., Levis M., et al. Prognostic Role of Pre-Radiation Therapy (18)F-Fluorodeoxyglucose Positron Emission Tomography for Primary Mediastinal B-Cell Lymphomas Treated with R-CHOP or R-CHOP-Like Chemotherapy Plus Radiation. Int J Radiat Oncol Biol Phys. 2016;95(4):1239–43. Doi: 10.1016/j.ijrobp.2016.02.057.
45. Martelli M., Ceriani L., Zucca E., et al.
46. Vassilakopoulos T.P., Pangalis G.A., Chatziioannou S., et al. PET/CT in primary mediastinal large B-cell lymphoma responding to rituximab-CHOP: An analysis of 106 patients regarding prognostic significance and implications for subsequent radiotherapy. Leukemia. 2016;30(1):238–42. Doi: 10.1038/leu.2015.120.
47. Pinnix C.C., Dabaja B., Ahmed M.A., et al. Single-institution experience in the treatment of primary mediastinal B cell lymphoma treated with immunochemotherapy in the setting of response assessment by 18fluorodeoxyglucose positron emission tomography. Int J Radiat Oncol Biol Phys. 2015;92(1):113–21. Doi: 10.1016/j.ijrobp.2015.02.006.
48. Kuruvilla J., Pintilie M., Tsang R., Nagy T., Keating A., Crump M. Salvage chemotherapy and autologous stem cell transplantation are inferior for relapsed or refractory primary mediastinal large B-cell lymphoma compared with diffuse large B-cell lymphoma. Leuk Lymphoma. 2008;49(7):1329–36. Doi: 10.1080/10428190802108870.
49. Moskowitz C.H., Hamlin P.A., Maragulia J., et al. Sequential dose-dense RCHOP followed by ICE consolidation (MSKCC protocol 01-142) without radiotherapy for patients with primary mediastinal large B cell lymphoma. Blood (ASH Annual Meeting Abstracts). 2010;118:Abstract 420.
50. 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;77:1053–60. Doi: 10.1007/s00280-016-3024-8.
51. 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.
52. NCCN Guidelines Version 5.2022 Primary Mediastinal Large B-Cell Lymphoma.
53. Sehn L.H., Antin J.H., Shulman L.N., et al. Primary diffuse large B-cell lymphoma of the mediastinum: outcome following high-dose chemotherapy and autologous hematopoietic cell transplantation. Blood. 1998;91(2):717–23.
54. Rodríguez J., Conde E., Gutiérrez A., et al. Primary mediastinal large cell lymphoma (PMBL): frontline treatment with autologous stem cell transplantation (ASCT). The GEL-TAMO experience. Hematol Oncol. 2008 26(3):171–78. Doi: 10.1002/hon.858.
55. Liu X., Deng T., Guo X., et al. A retrospective analysis of outcomes for primary mediastinallarge B-cell lymphoma treated with RCHOPfollowed by radiotherapy or front-line autologous stem cell transplantation. Hematology. 2017;22(5):258–64. Doi: 10.1080/10245332.2016.1258846.
56. 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.
57. Общероссийский национальный союз «Ассоциация онкологов России». Региональная общественная организация «Общество онкогематологов». Некоммерческое партнерство содействия развитию гематологии и трансплантологии костного мозга «Национальное гематологическое общество». Региональная общественная организация Национальное общество детских гематологов и онкологов. Клинические рекомендации. Агрессивные нефолликулярные лимфомы – диффузная крупноклеточная В-клеточная лимфома, первичная медиастинальная В-клеточная лимфома, лимфома Беркитта. 2020.
58. Higgins J.P., Warnke R.A. CD30 expression is common in mediastinal large B-cell lymphoma. Am J Clin Pathol. 1999;112(2):241–47. Doi: 10.1093/ajcp/112.2.241.
59. Svoboda J., Bair S.M., Landsburg D.J., Dwivedy Nasta S., et al. Brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone as frontline treatment for patients with CD30-positive B-cell lymphomas. Haematologica. 2021;106(6):1705–13. Doi: 10.3324/haematol.2019.238675.
60. Mottok A., Hung S.S., Chavez E.A., et al. Integrative genomic analysis identifies key pathogenic mechanisms in primary mediastinal large B-cell lymphoma. Blood. 2019; 134(10):802–13. Doi: 10.1182/blood.2019001126.
Об авторах / Для корреспонденции
Автор для связи: Лариса Валентиновна Филатова, д.м.н., доцент, ведущий науч. сотр. научного отдела инновационных методов терапевтической онкологии и реабилитации, Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова, Санкт-Петербург, Россия; larisa_filatova@list.ru">href="mailto:larisa_filatova@list.ru">larisa_filatova@list.ru
ORCID:
Л.А. Крамынин (Leonid A. Kramynin), https://orcid.org/0000-0003-4542-8353
Л.В. Филатова (Larisa V. Filatova), https://orcid.org/0000-0002-0728-4582
С.С. Елхова (Svetlana S. Elkhova), https://orcid.org/0000-0002-1691-0549
А.К. Ковязин (Aleksei K. Koviazin), https://orcid.org/0000-0001-5091-3711
Т.Ю. Семиглазова (Tatiana Yu. Semiglazova), https://orcid.org/0000-0002-4305-6691
