Front-Line Management of Mantle Cell Lymphoma in Canada: A Practical, Risk-Adapted Approach
Résumé
Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma (NHL) that accounts for approximately 5–7% of all lymphomas.1 Its clinical presentation is heterogeneous, ranging from an indolent leukemic non-nodal subtype that may be managed with observation to highly aggressive disease characterized by TP53 alterations, blastoid or pleomorphic morphology, and high Ki-67 expression. Although relatively uncommon, an estimated 500–600 new cases are diagnosed annually in Canada,2 underscoring the importance of optimizing evidence-based management strategies. In this review, we discuss front-line treatment approaches for MCL within the Canadian practice landscape.
Références
Armitage JO, Longo DL. Mantle-cell lymphoma. N Engl J Med. 2022;386(26):2495-506.
Anglin P, Elia-Pacitti J, Eberg M, Muratov S, Kukaswadia A, Sharma A, et al. Estimating the associated burden of illness and healthcare utilization of newly diagnosed patients aged ≥65 with mantle cell lymphoma (MCL) in Ontario, Canada. Curr Oncol. 2023;30(6):5529-45.
Abrisqueta P, Scott DW, Slack GW, Steidl C, Mottok A, Gascoyne RD, et al. Observation as the initial management strategy in patients with mantle cell lymphoma. Ann Oncol. 2017;28(10):2489-95.
McCulloch R, Smith A, Wainman B, Ingram W, Lewis A, Hawkins M, et al. 40% of Females with mantle cell lymphoma are managed with initial observation: results from the MCL biobank observational study. Blood. 2019;134(Supplement_1):2821-.
Kumar A, Ying Z, Alperovich A, Dogan A, Hamlin P, Moskowitz C, et al. Clinical presentation determines selection of patients for initial observation in mantle cell lymphoma. Haematologica. 2019;104(4):e163-e6.
Romaguera JE, Medeiros LJ, Hagemeister FB, Fayad LE, Rodriguez MA, Pro B, et al. Frequency of gastrointestinal involvement and its clinical significance in mantle cell lymphoma. Cancer. 2003;97(3):586-91.
Salar A, Juanpere N, Bellosillo B, Domingo-Domenech E, Espinet B, Seoane A, et al. Gastrointestinal involvement in mantle cell lymphoma: a prospective clinic, endoscopic, and pathologic study. Am J Surg Pathol. 2006;30(10):1274-80.
Skrypets T, Ferrari C, Nassi L, Margiotta Casaluci G, Puccini B, Mannelli L, et al. 18F-FDG PET/CT cannot substitute endoscopy in the staging of gastrointestinal involvement in mantle cell lymphoma. a retrospective multi-center cohort analysis. J Pers Med. 2021;11(2):123.
Leitch HA, Gascoyne RD, Chhanabhai M, Voss NJ, Klasa R, Connors JM. Limited-stage mantle-cell lymphoma. Ann Oncol. 2003;14(10):1555-61.
Rosenbluth BD, Yahalom J. Highly effective local control and palliation of mantle cell lymphoma with involved-field radiation therapy (IFRT). Int J Radiat Oncol Biol Phys. 2006;65(4):1185-91.
Bernard M, Tsang RW, Le LW, Hodgson DC, Sun A, Wells W, et al. Limited-stage mantle cell lymphoma: treatment outcomes at the Princess Margaret Hospital. Leuk Lymphoma. 2013;54(2):261-7.
Dabaja BS, Zelenetz AD, Ng AK, Tsang RW, Qi S, Allen PK, et al. Early-stage mantle cell lymphoma: a retrospective analysis from the International Lymphoma Radiation Oncology Group (ILROG). Ann Oncol. 2017;28(9):2185-90.
Eskelund CW, Kolstad A, Jerkeman M, Raty R, Laurell A, Eloranta S, et al. 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau. Br J Haematol. 2016;175(3):410-8.
Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, et al. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d’Etude des Lymphomes de l’Adulte. Blood. 2013;121(1):48-53.
Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, et al. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016;388(10044):565-75.
Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, et al. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017;377(13):1250-60.
Hermine O, Jiang L, Walewski J, Bosly A, Thieblemont C, Szymczyk M, et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: long-term follow-up of the randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023;41(3):479-84.
Villa D, Sehn LH, Savage KJ, Toze CL, Song K, den Brok WD, et al. Bendamustine and rituximab as induction therapy in both transplant-eligible and -ineligible patients with mantle cell lymphoma. Blood Adv. 2020;4(15):3486-94.
Alzahrani M, Gerrie AS, Sehn LH, Scott DW, Venner CP, Savage KJ, et al. Therapeutic advances and gradual improvement in overall survival in mantle cell lymphoma over four decades. Br J Haematol. 2025.
Villa D, Hoster E, Hermine O, Klapper W, Szymczyk M, Bosly A, et al. Bendamustine or high-dose cytarabine based induction with rituximab in transplant-eligible mantle cell lymphoma. Blood Adv. 2022;6(18):5285-94.
Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, et al. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008;112(7):2687-93.
Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R, et al. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005;105(7):2677-84.
Hoster E, Pott C. Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment. Hematology. 2016;2016(1):437-45.
Dreyling M, Doorduijn J, Giné E, Jerkeman M, Walewski J, Hutchings M, et al. Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network. Lancet. 2024;403(10441):2293-306.
Dreyling M, Doorduijn JK, Gine E, Jerkeman M, Walewski J, Hutchings M, et al. Role of autologous stem cell transplantation in the context of ibrutinib containing first-line treatment in younger patients with mantle cell lymphoma: results from the Randomized Triangle Trial by the European MCL Network. Blood. 2024;144(Supplement 1):240.
Fenske TS, Wang XV, Till BG, Blum KA, Lunning M, Lazarus HM, et al. Lack of benefit of autologous hematopoietic cell transplantation (auto-HCT) in mantle cell lymphoma (MCL) patients (pts) in first complete remission (CR) with undetectable minimal residual disease (uMRD): initial report from the ECOG ACRIN EA4151 phase 3 randomized trial. Blood. 2024;144(Supplement 2):LBA-6-LBA.
Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Trneny M, Geisler CH, et al. Treatment of older patients with mantle-cell lymphoma. N Engl J Med. 2012;367(6):520-31.
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):248-56.
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):984-91.
Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013;381(9873):1203-10.
Rummel MJ, Knauf W, Goerner M, Soeling U, Lange E, Hertenstein B, et al. Two years rituximab maintenance vs. observation after first-line treatment with bendamustine plus rituximab (B-R) in patients with mantle cell lymphoma: First results of a prospective, randomized, multicenter phase II study (a subgroup study of the StiL NHL7-2008 MAINTAIN trial). J Clin Oncol. 2016;34(15_suppl):7503.
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):541-54.
Wang Y, Larson MC, Hwang SR, Villa D, Kugathasan L, Kumar A, et al. Benefit of rituximab maintenance after first-line bendamustine-rituximab in patients with mantle cell lymphoma. Blood Adv. 2026;10(4):1372 80.
Wang ML, Jurczak W, Jerkeman M, Trotman J, Zinzani PL, Belada D, et al. Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma. N Engl J Med. 2022;386(26):2482-94.
Wang M, Salek D, Belada D, Song Y, Jurczak W, Kahl BS, et al. Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma. J Clin Oncol. 2025;43(20):2276-84.
Minson A, Hamad N, Di Ciaccio P, Talaulikar D, Ku M, Ratnasingam S, et al. Death from mantle cell lymphoma limits sequential therapy, particularly after first relapse: Patterns of care and outcomes in a series from Australia and the United Kingdom. Br J Haematol. 2024;204(2):548-54.
George S, Seung SJ, Thibault S, Wong A, Hamilton M, Prica A. 609 | Real-world treatment patterns, clinical outcomes and burden of illness of autologous stem-cell transplant ineligible patients with mantle cell lymphoma in Ontario, Canada. Hematol Oncol. 2025;43(S3):e609_70096.
Wang Y, Larson MC, Hwang SR, Villa D, Kugathasan L, Kumar A, et al. Mantle cell lymphoma outcomes following sequential first-line bendamustine-rituximab and second-line Bruton’s tyrosine kinase inhibitor therapy. Blood Cancer J. 2026.
Lewis DJ, Jerkeman M, Sorrell L, Wright D, Glimelius I, Poulsen CB, et al. Ibrutinib and rituximab versus immunochemotherapy in patients with previously untreated mantle cell lymphoma (ENRICH): a randomised, open-label, phase 2/3 superiority trial. Lancet. 2025;406(10514):1953-68.
Rampotas A, Wilson MR, Lomas O, Denny N, Leary H, Ferguson G, et al. Treatment patterns and outcomes of unfit and elderly patients with mantle cell lymphoma unfit for standard immunochemotherapy: A UK and Ireland analysis. Br J Haematol. 2021;194(2):365-77.
Jerkeman M, Wader KF, Glimelius I, Pasanen A, Kim WS, Hansen LK, et al. Acalabrutinib and rituximab in elderly patients with newly diagnosed mantle cell lymphoma including a matched population based external comparator- the Nordic Lymphoma Group NLG-MCL8 (ALTAMIRA) phase II trial. Blood. 2024;144(Supplement 1):747.
Eskelund CW, Dahl C, Hansen JW, Westman M, Kolstad A, Pedersen LB, et al. TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy. Blood. 2017;130(17):1903-10.
Kumar A, Soumerai J, Abramson JS, Barnes JA, Caron P, Chhabra S, et al. Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutation. Blood. 2025;145(5):497-507.
Hawkes E, Romejko-Jarosinska J, Jurczak W, Iyengar S, Costa A, Shah N, et al. Acalabrutinib plus venetoclax and rituximab in patients with treatment-naive (TN) mantle cell lymphoma (MCL): Results from the phase 2 TrAVeRse study. Blood. 2025;146(Supplement 1):884.
Wang M, Hoffmann MS, Wrobel T, Trneny M, Belada D, Demirkan F, et al. Efficacy and safety of first-line ibrutinib plus venetoclax in patients with mantle cell lymphoma (MCL) who were older or had TP53 mutations in the SYMPATICO study. J Clin Oncol. 2025;43(16_suppl):7017.
Tilch M-K, Schmidt C, Trneny M, Gine E, Hermine O, Ohler A, et al. Trials in Progress: Carman - an international, randomized phase ii study evaluating early treatment intensification in patients with high risk mantle cell lymphoma using CAR-T-cell treatment after an abbreviated induction therapy with rituximab and ibrutinib and 6 months ibrutinib maintenance (Arm A) as compared to standard of care induction and maintenance (Arm B). Blood. 2024;144(Supplement 1):4422.3-.3.
Jain P, Ahmed S, Ok CY, Nair R, Fetooh A, Hill H, et al. Acalabrutinib plus rituximab followed by brexucabtagene autoleucel for frontline treatment of high-risk mantle cell lymphoma: The window-3 clinical trial. Blood. 2025;146(Supplement 1):666.
Phillips T, Chen L, Barnhizer T, Herrera A, Shouse G, Ermann D, et al. Interim analysis of the phase II study of glofitamab, lenaliomide and venetoclax (GLOVe) in untreated patients w/ high-risk mantle cell lymphoma. response and safety outcomes after the completion of stage 1 of 2 enrollment. Blood. 2025;146(Supplement 1):883.
Téléchargements
Publié
Comment citer
Numéro
Rubrique
Licence
© Actualité hématologique au Canada 2026
Cette œuvre est sous licence Creative Commons Attribution - Pas d'Utilisation Commerciale - Pas de Modification 4.0 International.
