Maintenance Therapy for CD20+ Indolent Lymphoma: Who Should Receive Maintenance?


  • Edward Koo, MD Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario
  • David A. Macdonald, MD, FRCPC Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario



Maintenance rituximab (MR) has been a mainstay of treatment in Canada for CD20‑positive indolent lymphoma for two decades. The adoption of MR into clinical practice occurred after the publication of the EORTC 20981 trial. This trial showed a significant improvement in progression free survival (PFS) with two years of MR versus observation after induction therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with relapsed follicular lymphoma (FL). The use of MR was broadly extended to include its use in the front‑line setting, following any R-containing inductions and including all CD20-positive indolent lymphoma histologies.

Automatic recommendations for MR became the standard practice for most patients. Given the recent changes to standard induction regimens in some indications, and with heightened concerns about infectious complications during B-cell depleting therapy, the recommendation for the use of MR should no longer be considered automatic. This review offers a balanced perspective of the evidence for MR.

Author Biographies

Edward Koo, MD, Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario

Dr. Edward Koo is a fourth-year resident in the Adult Hematology Program at the University of Ottawa. He completed medical school at McMaster University followed by residency in Internal Medicine at Dalhousie University.

David A. Macdonald, MD, FRCPC, Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario

Dr. David Macdonald is a hematologist in the Malignant Hematology Group at the Ottawa Hospital, and Assistant Professor at the University of Ottawa. He is a member of the Scientific Advisory Board for Lymphoma Canada and is a contributor to the lymphoma working group of CCTG. His clinical practice focuses on lymphoma and chronic lymphocytic leukemia, and his research interests centre on clinical trials of novel therapies in lymphoma and CLL.


van Oers MH, Van Glabbeke M, Giurgea L, et al. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010;28(17):2853-2858. doi:10.1200/JCO.2009.26.5827

Le M, Ghazawi FM, Alakel A, Netchiporouk E, Rahme E, Zubarev A, et al. Incidence and mortality trends and geographic patterns of follicular lymphoma in Canada. Curr Oncol. 2019;26(4):e473-e481. doi: 10.3747/co.26.4625

Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, et al. Sustained progression-free survival benefit of rituximab maintenance in patients with follicular lymphoma: long-term results of the PRIMA study. J Clin Oncol. 2019;37(31):2815-2824. doi:10.1200/JCO.19.01073

Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, et al. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019;37(12):984-991. doi:10.1200/JCO.18.00605

Rummel MJ, Maschmeyer G, Ganser A, Heider A, von Gruenhagen U, Losem C, et al. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: nine-year updated results from the StiL NHL1 study. J Clin Oncol. 2017;35(15_suppl):7501. doi: 10.1200/JCO.2017.35.15_suppl.7501

Kahl BS, Burke JM, van der Jagt R, Chang J, Wood P, Hawkins TE, et al. Assessment of maintenance rituximab after first-line bendamustine-rituximab in patients with follicular lymphoma: an analysis from the BRIGHT trial. Blood. 2017;130 (Supplement 1):484. doi: 10.1182/blood.V130.Suppl_1484.1484

Hill BT, Nastoupil LJ, Winter A, Becnel M, Cerhan JR, Habermann TM, et al. Maintenance rituximab or observation after frontline treatment with bendamustine‐rituximab for follicular lymphoma. Br J Haematol. 2018;184(4):524-535. doi: 10.1111/bjh.15720

Rummel M, Buske C, Hertenstein B, Lerchenmüller C, Koenigsmann M, Lange E, et al. Four versus two years of rituximab maintenance (R-maintenance) following bendamustine plus rituximab (B-R): initial results of a prospective, randomized multicenter phase 3 study in first-line follicular lymphoma (the StiL NHL7-2008 MAINTAIN study). Blood. 2018;130 (Supplement 1):483. doi: 10.1182/blood.V130.Suppl_1.483.483

Sarkozy C, Maurer MJ, Link BK, Ghesquieres H, Nicolas E, Thompson CA, et al. Cause of death in follicular lymphoma in the first decade of the rituximab era: a pooled analysis of French and US Cohorts. J Clin Oncol. 2019;37(2):144-152. doi: 10.1200/JCO.18.00400

Townsend W, Hiddemann W, Buske C, Cartron G, Cunningham D, Dyer MJ, et al. Obinutuzumab versus rituximab immunochemotherapy in previously untreated iNHL: final results from the GALLIUM study. Hemasphere. 2023;7(7):e919. doi:10.1097/HS9.0000000000000919

Suleman A, Aktar SJ, Ante Z, Liu N, Chan K, Cheung MC, et al. Outcomes of patients with indolent lymphoma treated with bendamustine plus rituximab compared to rituximab plus CVP or CHOP chemoimmunotherapy in Ontario. Br J Haematol. 2023;202(6):1104-1118. doi: 10.1111/bjh.18972

Kahl BS, Jegede O, Peterson CG, Swinnen LJ, Habermann TM, Schuster SJ, et al. Long-term follow-up of the RESORT study (E4402): a randomized phase III comparison of two different rituximab dosing strategies for low–tumor burden follicular lymphoma. J Clin Oncol. 2024;42(7):774-778. doi:10.1200/JCO.23.01912

Kluin‐Nelemans HC, Hoster E, Hermine O, Walewski J, Geisler CH, Trneny M, et al. Treatment of older patients with mantle cell lymphoma (MCL): long-term follow-up of the randomized European MCL Elderly trial. J Clin Oncol. 2020;38(3):248-256. doi: 10.1200/JCO.19.01294

Martin P, Cohen JB, Wang M, Kumar A, Hill B, Villa D, et al. Treatment outcomes and roles of transplantation and maintenance rituximab in patients with previously untreated mantle cell lymphoma: results from large real-world cohorts. J Clin Oncol. 2023;41(3):541-554. doi:10.1200/JCO.21.02698

Sarkozy C, Thieblemont C, Obéric L, Moreau A, Bouabdallah K, Damaj G, et al. Very long-term follow-up of rituximab maintenance in young patients with mantle cell lymphoma included in the LYMA trial, a LYSA study. J Clin Oncol. 2024;42(7):769-773. doi:10.1200/JCO.23.01586

Vidal L, Gafter‐Gvili A, Dreyling M, Ghielmini M, Witzens‐Harig M, Shpilberg O, et al. Maintenance treatment for patients with mantle cell lymphoma. Hemasphere. 2018;2(4):e136. doi:10.1097/HS9.0000000000000136

Saurabh Zanwar, Abeykoon JP. Treatment paradigm in Waldenström macroglobulinemia: frontline therapy and beyond. Ther Adv Hematol. 2022;13:20406207221093962. doi:10.1177/20406207221093962

Rummel MJ, Lerchenmuller CA, Hensel M, Goerner M, Buske C, Schulz H, et al. Two years rituximab maintenance vs. observation after first line treatment with bendamustine plus rituximab (B-R) in patients with Waldenström’s macroglobulinemia (MW): results of a prospective, randomized, multicenter phase 3 study (the StiL NHL7-2008 MAINTAIN trial). Blood. 2019;134(Supplement_1):343. doi: 10.1182/blood-2019-121909

Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, et al. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016;173(6):867-875. doi: 10.1111/bjh.14007

Wirth SRM, Podar K, Pecherstorfer M, Wohlfarth P, Jaeger U, Singer J. Evaluation of antibody responses in patients with B-Cell malignancies after two and three doses of Anti-SARS-CoV-2 S vaccination-a retrospective cohort study. Cancers (Basel). 2023;15(2):524. doi: 10.3390/cancers15020524

Liatsou E, Ntanasis-Stathopoulos I, Lykos S, Ntanasis-Stathopoulos A, Gavriatopoulou M, Psaltopoulou T, et al. Adult patients with cancer have impaired humoral responses to complete and booster COVID-19 vaccination, especially those with hematologic cancer on active treatment: a systematic review and meta-analysis. Cancers (Basel). 2023;15(8):2266. doi: 10.3390/cancers15082266

Duléry R, Lamure S, Delord M, Di Blasi R, Chauchet A, Hueso T, et al. Prolonged in-hospital stay and higher mortality after Covid-19 among patients with non-Hodgkin lymphoma treated with B-cell depleting immunotherapy. Am J Hematol. 2021;96(8):934-944. doi: 10.1002/ajh.26209

Kow CS, Ramachandram DS, Hasan SS, Thiruchelvam K. Systematic review and meta-analysis of anti-CD20 treatments in patients with COVID-19: an assessment of severe illness and mortality outcomes. Inflammopharmacology. 2023;31(6):3339-3355. doi: 10.1007/s10787-023-01349-z



How to Cite

Koo E, Macdonald DA. Maintenance Therapy for CD20+ Indolent Lymphoma: Who Should Receive Maintenance?. Can Hematol Today [Internet]. 2024 Apr. 25 [cited 2024 May 20];3(1):44–50. Available from: