Challenges and perspectives of first-line therapy in patients with diffuse B-cell lymphoma: A review
- Authors: Babicheva L.G.1, Poddubnaya I.V.1
-
Affiliations:
- Russian Medical Academy of Continuous Professional Education
- Issue: Vol 25, No 2 (2023)
- Pages: 178-184
- Section: CLINICAL ONCOLOGY
- URL: https://journals.rcsi.science/1815-1434/article/view/132815
- ID: 132815
Cite item
Full Text
Abstract
The neoplasm we refer to as diffuse large B-cell lymphoma (DLBCL) consists of many different subtypes that should not be subject to a single standardized treatment. Critical at the diagnostic stage is the identification of rare (5–10%) but extremely aggressive variants – high grade B-cell lymphomas with MYC and BCL2 and/or BCL6 double-hit (DH) or triple-hit (TH) rearrangement, in which intensive chemoimmunotherapy programs should be applied. The main and most frequent variant of the heterogeneous group of B-cell lymphomas discussed in this publication is diffuse large B-cell lymphoma, not otherwise specified (NOS). Two immunohistochemical subtypes of DLBCL NOS are distinguished, GCB and non-GCB. According to cell of origin, the DLBCL NOS is divided into GCB, ABC, and an unclassified (U) subtypes. In addition, DLBCL NOS includes MYC and BCL2 double-expressor lymphoma (DEL), which is not a unique biological entity, occurs in both GCB and non-GCB subtypes of DLBCL, and is associated with a worse prognosis. Over the past two decades, DLBCL NOS, which accounts for more than 80% of all cases, has been the subject of a growing number of molecular studies that have identified prognostic factors that are being actively introduced into real-world clinical practice. Since the turn of the century, the R-CHOP regimen has been considered the most frequent first line therapy approach for DLBCL NOS, achieving long-term remissions in 60–70% of patients. The worst outcomes when using R-CHOP are recorded in groups at high risk of progression according to the International Prognostic Index (IPI – 3–5), as well as in the presence of unfavorable molecular genetic characteristics of the tumor, such as DEL or ABC subtype of DLBCL NOS. These patient populations benefited the most from the inclusion of polatuzumab vedotin in the initial therapy regimen (Pola-R-CHP). This approach reduced the risk of progression and death in patients with high-risk DLBCL by 30%, reducing the need for second-line therapy by 34%, which can be considered a breakthrough in the last 20 years of searching for improving the "gold standard" of first-line therapy and potentially defining a new standard of therapy for primary patients with high-risk DLBCL.
Full Text
##article.viewOnOriginalSite##About the authors
Lali G. Babicheva
Russian Medical Academy of Continuous Professional Education
Author for correspondence.
Email: lalibabicheva@mail.ru
ORCID iD: 0000-0001-8290-5564
Cand. Sci. (Med.)n Medical Academy of Continuous Professional Education
Russian Federation, MoscowIrina V. Poddubnaya
Russian Medical Academy of Continuous Professional Education
Email: ivprectorat@inbox.ru
ORCID iD: 0000-0002-0995-1801
D. Sci. (Med.), Prof., Acad. RASn Medical Academy of Continuous Professional Education
Russian Federation, MoscowReferences
- 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
- Wan M, Hong H, Li X, et al. Prognosis Evaluation of the Progression of Diffuse Large B-Cell Lymphoma within 24 Months. Ann Hematol Oncol. 2022;9(3):1398.
- 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. doi: 10.1093/annonc/mdy203
- Cheson BD, Fisher RI, Barrington SF, et al; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Español de Médula Ósea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. 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
- Zelenetz AD, Gordon LI, Abramson JS, et al. NCCN Guidelines insights: B-cell lymphomas, Version 3.2019. J Natl Compr Canc Netw. 2019;17(6):650-61. doi: 10.6004/jnccn.2019.0029
- Johnson NA, Slack GW, Savage KJ, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30(28):3452-9. doi: 10.1200/JCO.2011.41.0985
- Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503-11. doi: 10.1038/35000501
- Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275-82. doi: 10.1182/blood-2003-05-1545
- Khan AB, Barrington SF, Mikhaeel NG, et al. PET-CT staging of DLBCL accurately identifies and provides new insight into the clinical significance of bone marrow involvement. Blood. 2013;122(1):61-7. doi: 10.1182/blood-2012-12-473389
- Alzahrani M, El-Galaly TC, Hutchings M, et al. The value of routine bone marrow biopsy in patients with diffuse large B-cell lymphoma staged with PET/CT: a Danish-Canadian study. Ann Oncol. 2016;27(6):1095-9. doi: 10.1093/annonc/mdw137
- The 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
- Sehn LH, Berry B, Chhanabhai M, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007;109(5):1857-61. doi: 10.1182/blood-2006-08-038257
- Zhou Z, Sehn LH, Rademaker AW, et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014;123(6):837-42. doi: 10.1182/blood-2013-09-524108
- Shi X, Liu X, Li X, et al. Risk Stratification for Diffuse Large B-Cell Lymphoma by Integrating Interim Evaluation and International Prognostic Index: A Multicenter Retrospective Study. Front Oncol. 2021;11:754964. doi: 10.3389/fonc.2021.754964
- Tilly H, Gomes da Silva M, Vitolo U, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl. 5):v116-25. doi: 10.1093/annonc/mdv304
- Schmitz N, Zeynalova S, Nickelsen M, et al. CNS International Prognostic Index: a risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2016;34(26):3150-6. doi: 10.1200/JCO.2015.65.6520
- Lin Z, Chen X, Liu L, et al. The role of central nervous system (CNS) prophylaxis in preventing DLBCL patients from CNS relapse: A network meta-analysis. Crit Rev Oncol Hematol. 2022;176:103756. doi: 10.1016/j.critrevonc.2022.103756
- Hutchings M, Ladetto M, Buske C, et al. ESMO Consensus Conference on malignant lymphoma: management of ‘ultra-high-risk’ patients. Ann Oncol. 2018;29(8):1687-700. doi: 10.1093/annonc/mdy167
- Поддубная И.В., Паровичникова Е.Н., Каприн А.Д., Варфоломеева С.Р. Клинические рекомендации Агрессивные нефолликулярные лимфомы – диффузная крупноклеточная В-клеточная лимфома, первичная медиастинальная В-клеточная лимфома, лимфома Беркитта 2022 г. [Poddubnaya IV, Parovichnikova EN, Kaprin AD, Varfolomeeva SR. Klinicheskie rekomendatsii Agressivnye nefollikuliarnye limfomy – diffuznaia krupnokletochnaia V-kletochnaia limfoma, pervichnaia mediastinal'naia V-kletochnaia limfoma, limfoma Berkitta 2022 g. (in Russian)].
- Park S, Hong J, Hwang I, et al. Comprehensive geriatric assessment in elderly patients with newly diagnosed aggressive non-Hodgkin lymphoma treated with multi-agent chemotherapy. J Geriatr Oncol. 2015;6(6):470-8. doi: 10.1016/j.jgo.2015.10.183
- Merli F, Luminari S, Tucci A, et al. Simplified geriatric assessment in older patients with diffuse large B-cell lymphoma: the prospective Elderly Project of the Fondazione Italiana Linfomi. J Clin Oncol. 2021;39(11):1214-22. doi: 10.1200/JCO.20.02465
- Isaksen KT, Mastroianni MA, Rinde M, et al. A simplified frailty score predicts survival and can aid treatment-intensity decisions in older patients with DLBCL. Blood Adv. 2021;5(22):4771-82. doi: 10.1182/bloodadvances.2021004777
- 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
- Récher C, Coiffier B, Haioun C, et al. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011;378(9806):1858-67. doi: 10.1016/S0140-6736(11)61040-4
- Bartlett NL, Wilson WH, Jung SH, 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):1790-9. doi: 10.1200/JCO.18.01994
- Leonard JP, Kolibaba KS, Reeves JA, et al. Randomized phase II study of R-CHOP with or without bortezomib in previously untreated patients with non-germinal center B-cell-like diffuse large B-cell lymphoma. J Clin Oncol. 2017;35(31):3538-46. doi: 10.1200/JCO.2017.73.2784
- Younes A, Sehn LH, Johnson P, et al. Randomized phase III trial of Ibrutinib and Rituximab plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019;37(15):1285-95. doi: 10.1200/JCO.18.02403
- Nowakowski GS, Hong F, Scott DW, et al. Addition of Lenalidomide to R-CHOP improves outcomes in newly diagnosed diffuse large B-cell lymphoma in a randomized phase II US Intergroup study ECOG-ACRIN E1412. J Clin Oncol. 2021;39(12):1329-38. doi: 10.1200/JCO.20.01375
- Nowakowski GS, Chiappella A, Gascoyne R, et al. ROBUST: a phase III study of Lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2021;39(12):1317-28. doi: 10.1200/JCO.20.01366
- Habermann TM, Weller EA, Morrison VA, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(19):3121-7. doi: 10.1200/JCO.2005.05.1003
- Crump M, Leppä S, Fayad L, et al. Randomized, double-blind, phase III trial of enzastaurin versus placebo in patients achieving remission after first-line therapy for high-risk diffuse large B-cell lymphoma. J Clin Oncol. 2016;34(21):2484-92. doi: 10.1200/JCO.2015.65.7171
- Witzig TE, Tobinai K, Rigacci L, et al. Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial. Ann Oncol. 2018;29(3):707-14. doi: 10.1093/annonc/mdx764
- Thieblemont C, Tilly H, Gomes da Silva M, et al. Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone. J Clin Oncol. 2017;35(22):2473-81. doi: 10.1200/JCO.2017.72.6984
- Dornan D, Bennett F, Chen Y, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood. 2009;114(13):2721-9. doi: 10.1182/blood-2009-02-205500
- Sawalha Y, Maddocks K. Profile of Polatuzumab Vedotin in the Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma: A Brief Report on the Emerging Clinical Data. OncoTargets and Therapy. 2020;2020(13):5123-33. doi: 10.2147/OTT.S219449
- Polson AG, Yu SF, Elkins K, et al. Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. Blood. 2007;110(2):616-23. doi: 10.1182/blood-2007-01-066704
- Tilly H, Morschhauser F, Bartlett NL, et al. Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Lancet Oncol. 2019;20(7):998-1010. doi: 10.1016/S1470-2045(19)30091-9
- Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022;386(4):351-63. doi: 10.1056/NEJMoa2115304
- Melchardt T, Egle A, Greil R. How I treat diffuse large B-cell lymphoma. ESMO Open. 2023;8(1):100750. doi: 10.1016/j.esmoop.2022.100750
- Boissard F, Tilly H, Lenz G, et al. Epidemiological Impact of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin and Prednisone (Pola-R-CHP) Use in Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL) in Terms of Second Line (2L) Treatment: An Ad Hoc Analysis from the POLARIX Study. Blood. 2022;140(Suppl. 1):6645-7. doi: 10.1182/blood-2022-157904
- Poeschel V, Held G, Ziepert M, et al; FLYER Trial Investigators, German Lymphoma Alliance. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2019;394(10216):2271-81. doi: 10.1016/S0140-6736(19)33008-9
- Bologna S, Vander Borght T, Briere J, et al. Early positron emission tomography response-adapted treatment in localized diffuse large B-cell lymphoma (AAIPI=0): results of the phase 3 LYSA LNH 09-1B trial. Hematol Oncol. 2021;39(Suppl. 2):abstr 5. doi: 10.1002/hon.5_2879
- Pfreundschuh M. How I treat elderly patients with diffuse large B-cell lymphoma. Blood. 2010;116(24):5103-10. doi: 10.1182/blood-2010-07-259333
- Held G, Murawski N, Ziepert M, et al. Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. J Clin Oncol. 2014;32(11):1112-8. doi: 10.1200/JCO.2013.51.4505
- Pfreundschuh M, Christofyllakis K, Altmann B, et al. Radiotherapy to bulky disease PET-negative after immunochemotherapy in elderly DLBCL patients: results of a planned interim analysis of the first 187 patients with bulky disease treated in the OPTIMAL>60 study of the DSHNHL. J Clin Oncol. 2017;35(Suppl. 15):7506. doi: 10.1200/JCO.2017.35.15_suppl.7506.