Poddubnaya IV, Babicheva LG, Bariakh EA. Diffuse large B-cell lymphoma: strokes to the epidemiological portrait. A review. Journal of Modern Oncology. 2023;25(3). DOI: 10.26442/18151434.2023.3.202402
Диффузная В-клеточная крупноклеточная лимфома: штрихи к эпидемиологическому портрету
Poddubnaya IV, Babicheva LG, Bariakh EA. Diffuse large B-cell lymphoma: strokes to the epidemiological portrait. A review. Journal of Modern Oncology. 2023;25(3). DOI: 10.26442/18151434.2023.3.202402
Диффузная крупноклеточная В-клеточная лимфома (ДВККЛ) – это гетерогенное орфанное лимфопролиферативное заболевание, характеризующееся агрессивным течением, на долю которого приходится 30–40% всех неходжкинских лимфом. Ежегодно в России диагностируется примерно 3 тыс. первичных случаев ДВККЛ. Тенденция к неуклонному росту заболеваемости во всем мире и быстро меняющийся ландшафт лечения с внедрением инновационных опций требуют актуализации эпидемиологических данных. Несмотря на более глубокое понимание лимфомагенеза и молекулярной гетерогенности ДВККЛ, стандартом 1-й линии терапии остается режим R-CHOP, который получают подавляющее большинство (74%) пациентов в России и мире. Эффективность такого подхода сильно варьирует и зависит от ряда клинических, биологических и генетических факторов. В настоящее время наиболее эффективной и простой прогностической моделью является Международный прогностический индекс (IPI), согласно которому примерно 20% пациентов относятся к промежуточной/высокой группе риска раннего прогрессирования (IPI3-5) и требуют модификации терапии. После проведения стандартной иммунохимиотерапии 1-й линии 60–70% пациентов с ДВККЛ достигают длительной ремиссии с потенциалом излечения. К сожалению, возникновение рецидива или констатация рефрактерности заболевания у оставшихся 40% пациентов обусловливают крайне неблагоприятный прогноз с медианой общей выживаемости около 6 мес, с тенденцией к уменьшению с каждой последующей линией, обусловливая острую необходимость в разработке новых инновационных методов лечения пациентов с рецидивами ДВККЛ.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous orphan lymphoproliferative disease with an aggressive course, which accounts for 30–40% of all non-Hodgkin lymphomas. Approximately 3,000 new cases of DLBCL are diagnosed annually in Russia. The trend towards a steady increase in DLBCL incidence worldwide and the rapidly changing treatment landscape with the introduction of innovative options require the updating of epidemiological data. Despite a deeper understanding of the lymphomagenesis and molecular heterogeneity of DLBCL, the R-CHOP regimen remains the first-line standard of care for the vast majority (74%) of patients in Russia and worldwide. The effectiveness of this approach varies greatly and depends on several clinical, biological, and genetic factors. Currently, the most effective and simple prognostic model is the International Prognostic Index (IPI), according to which approximately 20% of patients are at intermediate/high risk of early progression (IPI3-5) and require therapy modification. After the first-line standard immunochemotherapy, 60–70% of DLBCL patients achieve long-term remission with the potential for cure. However, the occurrence of relapse or refractory disease in the remaining 40% of patients is associated with an abysmal prognosis with a median overall survival of about 6 months, which tends to decrease with each subsequent line, warranting an urgent need for new innovative treatments for patients with relapsed DLBCL.
1. Проект клинических рекомендаций 2022 «Агрессивные нефолликулярные лимфомы –диффузная крупноклеточная В-клеточная лимфома, первичная медиастинальная В-клеточная лимфома, лимфома Беркитта». Режим доступа: https://rusoncohem.ru/klinrec/agressivnye-nefollikulyarnye-limfomy-proekt-2021-2022. Ссылка активна на 15.05.2023 [Draft clinical guidelines 2022 “Aggressive non-follicular lymphomas – diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, Burkitt’s lymphoma.” Available at: https://rusoncohem.ru/klinrec/agressivnye-nefollikulyarnye-limfomy-proekt-2021-2022. Accessed: 15.05.2023 (in Russian)].
2. Sehn LH, Salles G. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021;384(9):842-58. DOI:10.1056/NEJMra2027612
3. National Cancer Institute. Cancer Stat Facts: NHL – Diffuse Large B-Cell Lymphoma (DLBCL). Available at: https://seer.cancer.gov/statfacts/html/dlbcl.html. Accessed: 15.05.2023.
4. Kanas G, Ge W, Quek RGW, et al. Epidemiology of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the United States and Western Europe: population-level projections for 2020–2025. Leukemia Lymphoma. 2022;63(1):54‑63. DOI:10.1080/10428194.2021.1975188
5. Состояние онкологической помощи населению России в 2020 году. Под ред. А.Д. Каприна, В.В. Cтаринского, А.О. Шахзадовой. М., 2021 [Sostoianiie onkologicheskoi pomoshchi naseleniiu Rossii v 2020 godu. Pod red. AD Kaprina, VV Ctarinskogo, AO Shakhzadovoi. Moscow, 2021 (in Russian)].
6. Состояние онкологической помощи населению России в 2021 году. Под ред. А.Д. Каприна, В.В. Cтаринского, А.О. Шахзадовой. М., 2022 [Sostoianiie onkologicheskoi pomoshchi naseleniiu Rossii v 2021 godu. Pod red. AD Kaprina, VV Ctarinskogo, AO Shakhzadovoi. Moscow, 2022 (in Russian)].
7. Состояние онкологической помощи населению России в 2022 году. Под ред. А.Д. Каприна, В.В. Cтаринского, А.О. Шахзадовой. М., 2023 [Sostoianiie onkologicheskoi pomoshchi naseleniiu Rossii v 2022 godu. Pod red. AD Kaprina, VV Ctarinskogo, AO Shakhzadovoi. Moscow, 2023 (in Russian)].
8. Ghesquieres H, Cherblanc F, Belot A, et al. P1186: A large French real world multicentric prospective cohort of patients with lymphoma (REALYSA): description of the diffuse large B cell lymphoma patients in real world in France. Hemasphere. 2022;6 (Suppl.):1072-3. DOI:10.1097/01.HS9.0000847608.68270.ea
9. Бабичева Л.Г., Поддубная И.В. Первая линия терапии агрессивных неходжкинских лимфом в Российской клинической практике: данные исследования EQUILIBRIUM. Онкогематология. 2020;15(2):10-8 [Babicheva LG, Poddubnaya IV. The first-line therapy of aggressive non-Hodgkin’s lymphomas in Russian clinical practice: data from the EQUILIBRIUM study. Oncohematology. 2020;15(2):10-8 (in Russian)].
10. Maurer MJ, Ghesquières H, Jais JP, et al. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014;32:1066-73.
11. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-8.
12. Sehn LH, Donaldson J, Chhanabhai M, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005;23(22):5027-33. DOI:10.1200/JCO.2005.09.137
13. Sarkozy C, Sehn LH. Management of relapsed/refractory DLBCL. Best Pract Res Clin Haematol. 2018;31:209-16. DOI:10.1016/j.beha.2018.07.014.
14. Капланов К.Д., Волков Н.П., Клиточенко Т.Ю., и др. Результаты анализа регионального регистра пациентов с диффузной В-крупноклеточной лимфомой: факторы риска и проблемы иммунохимиотерапии. Клиническая онкогематология. 2019;12(2):154-64 [Kaplanov KD, Volkov NP, Klitochenko TYu, et al. Analysis Results of the Regional Registry of Patients with Diffuse Large B-cell Lymphoma: Risk Factors and Chemo-Immunotherapy Issues. Clinical Oncohematology. 2019;12(2):154-64 (in Russian)].
15. Maurer MJ, Habermann TM, Shi Q, et al. Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) enrolled on randomized clinical trials. Ann Oncol. 2018;29(8):1822-7.
16. Wang S, Wang L, Hu J, Qian W. Outcomes in refractory diffuse large B-cell lymphoma: results from a multicenter real-world study in China. Cancer Commun (Lond).
2021;41(3):229-39.
17. International Non-Hodgkin's 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
18. Ruppert AS, Dixon JG, Salles G, et al. International prognostic indices in diffuse large B-cell lymphoma: a comparison of IPI, R-IPI, and NCCN-IPI. Blood. 2020;135(23):2041-8. DOI:10.1182/blood.2019002729
19. Knauf W, Abenhardt W, Mohm J, et al. Similar effectiveness of R-CHOP-14 and -21 in diffuse large B-cell lymphoma-data from the prospective German Tumour Registry Lymphatic Neoplasms. Eur J Haematol. 2019;103(5):460-71. DOI:10.1111/ejh.13295
20. Wu JQ, Song YP, Su LP, et al. Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study. Chin Med J (Engl). 2018;131(15):1767-75.
DOI:10.4103/0366-6999.237401
21. McMillan AK, Phillips EH, Kirkwood AA, et al. Favourable outcomes for high-risk diffuse large B-cell lymphoma (IPI 3-5) treated with front-line R-CODOX‑M/R-IVAC chemotherapy: results of a phase 2 UK NCRI trial. Ann Oncol. 2020;31(9):1251-9. DOI:10.1016/j.annonc.2020.05.016
22. Philip T, Guglielmi C, Hagenbeek A, et al. Autologous Bone Marrow Transplantation as Compared with Salvage Chemotherapy in Relapses of Chemotherapy-Sensitive Non-Hodgkin's Lymphoma. N Engl J Med. 1995;333:1540-5.
23. Gisselbrecht C, Schmitz N, Mounier N, et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20+ diffuse large B-cell lymphoma: final analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma. J Clin Oncol. 2012;30:4462-9.
24. Von Matt S, Bacher U, Banz Y, et al. Outcome of Patients with Diffuse Large B-Cell Lymphoma Relapsing after Autologous Transplant before Availability of CAR-T Cell Treatment. Mediterr J Hematol Infect Dis. 2023;15(1):e2023025. DOI:10.4084/MJHID.2023.025
25. Van Den Neste E, Schmitz N, Mounier N, et al. Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study. Bone Marrow Transplant. 2016;51(1):51-7. DOI:10.1038/bmt.2015.213
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1. Draft clinical guidelines 2022 “Aggressive non-follicular lymphomas – diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, Burkitt’s lymphoma.” Available at: https://rusoncohem.ru/klinrec/agressivnye-nefollikulyarnye-limfomy-proekt-2021-2022. Accessed: 15.05.2023 (in Russian).
2. Sehn LH, Salles G. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021;384(9):842-58. DOI:10.1056/NEJMra2027612
3. National Cancer Institute. Cancer Stat Facts: NHL – Diffuse Large B-Cell Lymphoma (DLBCL). Available at: https://seer.cancer.gov/statfacts/html/dlbcl.html. Accessed: 15.05.2023.
4. Kanas G, Ge W, Quek RGW, et al. Epidemiology of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the United States and Western Europe: population-level projections for 2020–2025. Leukemia Lymphoma. 2022;63(1):54‑63. DOI:10.1080/10428194.2021.1975188
5. Sostoianiie onkologicheskoi pomoshchi naseleniiu Rossii v 2020 godu. Pod red. AD Kaprina, VV Ctarinskogo, AO Shakhzadovoi. Moscow, 2021 (in Russian).
6. Sostoianiie onkologicheskoi pomoshchi naseleniiu Rossii v 2021 godu. Pod red. AD Kaprina, VV Ctarinskogo, AO Shakhzadovoi. Moscow, 2022 (in Russian).
7. Sostoianiie onkologicheskoi pomoshchi naseleniiu Rossii v 2022 godu. Pod red. AD Kaprina, VV Ctarinskogo, AO Shakhzadovoi. Moscow, 2023 (in Russian).
8. Ghesquieres H, Cherblanc F, Belot A, et al. P1186: A large French real world multicentric prospective cohort of patients with lymphoma (REALYSA): description of the diffuse large B cell lymphoma patients in real world in France. Hemasphere. 2022;6 (Suppl.):1072-3. DOI:10.1097/01.HS9.0000847608.68270.ea
9. Babicheva LG, Poddubnaya IV. The first-line therapy of aggressive non-Hodgkin’s lymphomas in Russian clinical practice: data from the EQUILIBRIUM study. Oncohematology. 2020;15(2):10-8 (in Russian).
10. Maurer MJ, Ghesquières H, Jais JP, et al. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014;32:1066-73.
11. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-8.
12. Sehn LH, Donaldson J, Chhanabhai M, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005;23(22):5027-33. DOI:10.1200/JCO.2005.09.137
13. Sarkozy C, Sehn LH. Management of relapsed/refractory DLBCL. Best Pract Res Clin Haematol. 2018;31:209-16. DOI:10.1016/j.beha.2018.07.014.
14. Kaplanov KD, Volkov NP, Klitochenko TYu, et al. Analysis Results of the Regional Registry of Patients with Diffuse Large B-cell Lymphoma: Risk Factors and Chemo-Immunotherapy Issues. Clinical Oncohematology. 2019;12(2):154-64 (in Russian).
15. Maurer MJ, Habermann TM, Shi Q, et al. Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) enrolled on randomized clinical trials. Ann Oncol. 2018;29(8):1822-7.
16. Wang S, Wang L, Hu J, Qian W. Outcomes in refractory diffuse large B-cell lymphoma: results from a multicenter real-world study in China. Cancer Commun (Lond).
2021;41(3):229-39.
17. International Non-Hodgkin's 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
18. Ruppert AS, Dixon JG, Salles G, et al. International prognostic indices in diffuse large B-cell lymphoma: a comparison of IPI, R-IPI, and NCCN-IPI. Blood. 2020;135(23):2041-8. DOI:10.1182/blood.2019002729
19. Knauf W, Abenhardt W, Mohm J, et al. Similar effectiveness of R-CHOP-14 and -21 in diffuse large B-cell lymphoma-data from the prospective German Tumour Registry Lymphatic Neoplasms. Eur J Haematol. 2019;103(5):460-71. DOI:10.1111/ejh.13295
20. Wu JQ, Song YP, Su LP, et al. Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study. Chin Med J (Engl). 2018;131(15):1767-75.
DOI:10.4103/0366-6999.237401
21. McMillan AK, Phillips EH, Kirkwood AA, et al. Favourable outcomes for high-risk diffuse large B-cell lymphoma (IPI 3-5) treated with front-line R-CODOX‑M/R-IVAC chemotherapy: results of a phase 2 UK NCRI trial. Ann Oncol. 2020;31(9):1251-9. DOI:10.1016/j.annonc.2020.05.016
22. Philip T, Guglielmi C, Hagenbeek A, et al. Autologous Bone Marrow Transplantation as Compared with Salvage Chemotherapy in Relapses of Chemotherapy-Sensitive Non-Hodgkin's Lymphoma. N Engl J Med. 1995;333:1540-5.
23. Gisselbrecht C, Schmitz N, Mounier N, et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20+ diffuse large B-cell lymphoma: final analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma. J Clin Oncol. 2012;30:4462-9.
24. Von Matt S, Bacher U, Banz Y, et al. Outcome of Patients with Diffuse Large B-Cell Lymphoma Relapsing after Autologous Transplant before Availability of CAR-T Cell Treatment. Mediterr J Hematol Infect Dis. 2023;15(1):e2023025. DOI:10.4084/MJHID.2023.025
25. Van Den Neste E, Schmitz N, Mounier N, et al. Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study. Bone Marrow Transplant. 2016;51(1):51-7. DOI:10.1038/bmt.2015.213
Авторы
И.В. Поддубная*1, Л.Г. Бабичева1, Е.А. Барях1–3
1ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия; 2ГБУЗ «Городская клиническая больница №52» Департамента здравоохранения г. Москвы, Москва, Россия; 3ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
*ivprectorat@inbox.ru
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Irina V. Poddubnaya*1, Lali G. Babicheva1, Elena A. Bariakh1–3 1Russian Medical Academy of Continuous Professional Education, Moscow, Russia; 2City Clinical Hospital №52, Moscow, Russia; 3Pirogov Russian National Research Medical University, Moscow, Russia
*ivprectorat@inbox.ru