Skip to main content
SpringerLink
Log in

Treatment Strategies in Mantle Cell Lymphoma

  • Chapter
  • First Online:
Non-Hodgkin Lymphoma

Part of the book series: Cancer Treatment and Research ((CTAR,volume 165))

Abstract

Mantle cell lymphoma (MCL) is a distinct B-cell non-Hodgkin’s lymphoma (NHL) defined by the translocation t(11;14). MCL combines characteristics of both indolent and aggressive lymphomas, and it is incurable with conventional chemoimmunotherapy but has a more aggressive disease course. Minimal data exist on treatment of patients diagnosed with early-stage disease (stage I–II non-bulky), as this represents only a small portion of the patients diagnosed with MCL, but therapeutic options evaluated in retrospective studies include radiation or combination radiation and chemotherapy. There is a subset of patients with newly diagnosed MCL that can be observed without treatment, but the majority of patients will require treatment at diagnosis. Treatment is often based on age (≤65–70 years of age), comorbidities, and risk factors for disease. The majority of patients who are younger and without significant comorbidities are treated with intensive induction using combination chemoimmunotherapy regimens, many which include consolidation with autologous stem cell transplant (ASCT). Several regimens have been studied that show improved median progression-free survival (PFS) to 3–6 years in this population of patients. The majority of older patients (≥65–70 years of age) are treated with combination chemoimmunotherapy regimens with consideration of rituximab maintenance, with enrollment on a clinical trial encouraged. Therapy for relapsed disease is dependent on prior treatment, age, comorbidities, and toxicities but includes targeted therapies such as the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, the immunomodulatory agent lenalidomide, the proteasome inhibitor bortezomib, combination chemoimmunotherapy, ASCT, and allogeneic stem cell transplant in selected cases. Several novel agents and targeted therapies alone or in combination are currently being studied and developed in both the upfront and relapsed setting.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Swerdlow S, Campo E, Harris N et al (2008) WHO classification of tumors of hematopoietic and lymphoid tissues. World Health Organization, Lyon, pp 229–232

    Google Scholar 

  2. Anderson JR, Armitage JO et al (1998) Epidemiology of the non-Hodgkin’s lymphomas: distributions of the major subtypes differ by geographic locations. Non-Hodgkin’s lymphoma classification project. Ann Oncol 9(7):717–720

    Article  CAS  PubMed  Google Scholar 

  3. Zhou Y, Wang H et al (2008) Incidence trends of mantle cell lymphoma in the United States between 1992 and 2004. Cancerb 113(4):791–798

    Article  Google Scholar 

  4. International Non-Hodgkin’s Lymphoma Prognostic Factors Project (1993) A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med 329:987–994

    Article  Google Scholar 

  5. Hoster E, Dreyling M, Klapper W et al (2008) A new prognostic index (MIPI) for patients with advanced mantle cell lymphoma. Blood 111:558–565

    Article  CAS  PubMed  Google Scholar 

  6. Hernandez L, Fest T, Cazorla M, Teruya-Feldstein J, Bosch F, Peinado MA et al (1996) p53 gene mutations and protein overexpression are associated with aggressive variants of mantle cell lymphomas. Blood 87(8):3351–3359

    CAS  PubMed  Google Scholar 

  7. Greiner TC, Moynihan MJ, Chan WC, Lytle DM, Pedersen A, Anderson JR et al (1996) p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis. Blood 87(10):4302–4310

    CAS  PubMed  Google Scholar 

  8. Martinez A, Bellosillo B, Bosch F, Ferrer A, Marce S, Villamor N et al (2004) Nuclear surviving expression in mantle cell lymphoma is associated with cell proliferation and survival. Am J Pathol 164(2):501–510

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Raty R, Franssila K, Joensuu H, Teerenhovi L, Elonen E (2002) Ki-67 expression level, histological subtype, and the International Prognostic Index as outcome predictors in mantle cell lymphoma. Eur J Haematol 69(1):11–20

    Article  PubMed  Google Scholar 

  10. Cohen JB, Ruppert AS, Heerema NA et al (2012) Complex Karyotype (CK) is associated with a shortened progression-free survival (PFS) in patients with newly diagnosed mantle cell lymphoma. Blood A:2691

    Google Scholar 

  11. Sarkozy C, Terré C, Jardin F et al (2014) Complex karyotype in mantle cell lymphoma is a strong prognostic factor for the time to treatment and overall survival, independent of the MCL international prognostic index. Genes Chromo Cancer 53(1):106–116. doi:10.1002/gcc.22123

    Article  CAS  Google Scholar 

  12. Nodit L, Bahler D, Jacobs S et al (2003) Indolent mantle cell lymphoma with nodal involvement and mutated immunoglobulin heavy chain genes. Hum Pathol 34:1030–1034

    Article  CAS  PubMed  Google Scholar 

  13. Navarro A, Clot G, Royo C et al (2012) Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX22 expression have distinct biologic and clinical features. Cancer Res 72(20):5307–5316

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Leitch HA, GAscoyne RD, Chhanabhai M et al (2003) Limited-stage mantle-cell lymphoma. Ann Oncol 14:1555–1561

    Article  CAS  PubMed  Google Scholar 

  15. Martin P, Chadburn A, Christos P et al (2009) Outcome of deferred initial therapy in mantle cell lymphoma. J Clin Oncol 27:1209–1213

    Article  PubMed  Google Scholar 

  16. Romaguera J, Fayad L, Rodriquez MA et al (2005) High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol 23:7013–7023

    Article  CAS  PubMed  Google Scholar 

  17. Epner EM, Unger J, Miller T, Romzsa L, Spier C, Leblanc M, Fisher R (2007) A multi-center trial of hyperCVAD + rituxan in patients with newly diagnosed mantle cell lymphoma. Blood 110:A387

    Google Scholar 

  18. Bernstein SH, Epner E, Unger JM et al (2013) A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213. Ann Oncol 24:1587–1593

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Merli F, Luminari S, Ilariucci F, et al (2012) Rituximab plus hyper CVAD alternating with high dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma. A multicenter trial from GISL. Brit J Haematol 156:346–353

    Google Scholar 

  20. Dreyling M, Lenz G, Hoster E et al (2005) Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progress-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL network. Blood 105:2677–2684

    Article  CAS  PubMed  Google Scholar 

  21. Damon LE, Johnson JL, Niedzwiecki D et al (2009) Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol 27:6101–6108

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Kaplan LD, Jung S, Bartelet N et al (2013) Bortezomib maintenance (BM) versus consolidation (BC) following aggressive immunochemotherapy and autologous stem cell transplant (ASCT) for untreated mantle cell lymphoma (MCL): CALGB 50403. Hematol Oncol 31:A89

    Google Scholar 

  23. Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E, Nordic Lymphoma Group (2008) Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase II multicenter study by the Nordic Lymphoma Group. Blood 112:2687–2693

    Google Scholar 

  24. Geisler CH, Kolstad A, Laurell A et al (2012) Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem- cell support: still very long survival but late relapses do occur. Br J Haematol 158:355–362

    Article  CAS  PubMed  Google Scholar 

  25. Andersen NS, Pedersen L, Elonen E et al. (2003) Primary treatment with autologous stem cell transplantation in mantle cell lymphoma: outcome related to remission pretransplant. Eur J Haematol 71:73–80

    Google Scholar 

  26. Delarue R, Haioun C, Ribrag V et al (2013) CHOP and DHAP plus rituximab followed by autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL): a phase II study from the GELA. Blood 121:48–53

    Article  CAS  PubMed  Google Scholar 

  27. Pott C, Hoster E, Beldjord K, et al (2010) R-CHOP/R-DHAP compared to R-CHOP induction followed by high dose therapy with autologous stem cell transplantation induces higher rates of molecular remission in MCL: results of the MCL younger intergroup trial of the European MCL Network [abstract]. Blood 116:965

    Google Scholar 

  28. Budde LE, Guthric KA, Til BG et al (2011) Mantle Cell lymphoma international prognostic index but not pretransplantation induction regimen predicts survival for mantle-cell lymphoma receiving high-dose therapy and autologous stem-cell transplantation. J Clin Oncol 29:3023

    Google Scholar 

  29. Liu H, Johnson JL, Loval G et al (2012) Detection of minimal residual disease following induction chemoimmunotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909. Hematologica 97(4):579–585

    Article  CAS  Google Scholar 

  30. Pott C, Hoster E, Delfau-Larue MH et al (2010) Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study. Blood 115:3215–3223

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Foran JM, Cunningham D, Coiffier B (2000) Treatment of mantle-cell lymphoma with rituximab (chimeric anti-CD20 antibody): analysis of factors associated with response. Ann Oncol 11(1):117–121

    Article  PubMed  Google Scholar 

  32. Foran JM, Rohatiner AZ, Cunningham D et al (2000) European phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma and previously treated mantle-cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma. J Clin Oncol 18(2):317–324

    CAS  PubMed  Google Scholar 

  33. Ghielmini M, Schmitz SF, Cogliatti S et al (2005) Effect of single-agent rituximab given at the standard schedule or as prolonged treatment in patients with mantle cell lymphoma: a study of the Swiss Group for Clinical Cancer Research (SAKK). J Clin Oncol 23(4):705–711

    Article  CAS  PubMed  Google Scholar 

  34. Kluin-Nelemans JC, Hoster E, Walewski J, et al (2011) R-CHOP versus R-FC followed by maintenance with Rituximab versus interferon-Alfa: outcome of the first randomized trial for elderly patients with mantle cell lymphoma [abstract]. Blood 118:439

    Google Scholar 

  35. Rummel MJ, Niederle N, Maschmeyer G et al (2013) Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL): an open-label, multicentre, randomized, phase 3 non-inferiority trial. Lancet 381:1203–1210

    Article  CAS  PubMed  Google Scholar 

  36. Flinn IW, van der Jagt R, Kahl BS et al (2014) Open-label, randomized, noninferiority study of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of advanced indolent NHL or MCL: the BRIGHT study. Blood, Epub

    Google Scholar 

  37. Inward DJ, Fishkin PA, Hillman DW et al (2008) Long-term results of the treatment of patients with mantle cell lymphoma with cladribine (2-CDA) alone or 2-CDA and rituximab in the North Central Cancer Treatment Group. Cancer 113:108–116

    Article  Google Scholar 

  38. Advani RH, Buggy JJ, Sharman JP et al (2013) Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol 31:88–94

    Article  CAS  PubMed  Google Scholar 

  39. Wang ML, Rule S, Martin P et al (2013) Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 369:507

    Google Scholar 

  40. Budde LE, Guthric KA, Til BG et al (2011) Mantle cell lymphoma international prognostic index but not pretransplantation induction regimen predicts survival for mantle-cell lymphoma receiving high-dose therapy and autologous stem-cell transplantation. J Clin Oncol 29:3023

    Google Scholar 

  41. Habermann TM, Lossos IS, Justice G, Vose JM, Wiernik PH, McBride K, Wride K, Ervin-Haynes A, Takeshita K, Pietronigro D, Zeldis JB, Tuscano JM (2009) Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle-cell lymphoma. Brit J Haem 145:344–349

    Article  CAS  Google Scholar 

  42. Reeder CB, Witzig TE, Zinzani PL et al (2009) Efficacy and safety of lenalidomide oral monotherapy in patients with relapsed or refractory mantle-cell lymphoma: results from an international study (NHL-003) [abstract]. J Clin Oncol 27:8569

    Google Scholar 

  43. Zinzani PL, Vose JM, Czuczman MS, et al (2012) Phase II multicenter study of the safety and efficacy of single-agent lenalidomide in subjects with relapsed/refractory mantle cell lymphoma: long-term follow-up analysis of the nhl-003 study [abstract]. Blood 120:2738

    Google Scholar 

  44. Wang M, Fayad L, Wagner-Bartak N et al (2012) Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Lancet Oncol 13:716–723

    Article  PubMed  Google Scholar 

  45. Fisher RI, Bernstein SH, Kahl BS et al (2006) Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol 24:4867–4874

    Article  PubMed  Google Scholar 

  46. Goy A, Bernstein SH, Kahl BS et al (2009) Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analysis of the multicenter phase 2 PINNACLE study. Ann Oncol 20:520–525

    Article  CAS  PubMed  Google Scholar 

  47. Rummel MJ, Al-Batran SE, Kim SZ et al (2005) Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin’s lymphoma. J Clin Oncol 23:3383–3389

    Article  CAS  PubMed  Google Scholar 

  48. Robinson KS, Williams ME, van der Jagt RH, Cohen P, Herst JA, Tulpule A, Schwartzberg LS, Lemieux B, Cheson BD (2008) Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin’s lymphoma. J Clin Oncol 26:4473–4479

    Article  CAS  PubMed  Google Scholar 

  49. Friedberg JW, Vose JM, Kelly JL et al (2011) The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell lymphoma. Blood 117:2807–2812

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Till BG, Gooley TA, Crawford N et al (2008) Effect of remission status and induction chemotherapy regimen on outcome of autologous stem cell transplantation for mantle cell lymphoma. Leuk Lymphoma 49(6):1062–1073

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Tam CS, Bassett R, Ledesma C et al (2009) Mature results of the M.D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma. Blood 113:444–4152

    Google Scholar 

  52. Khouri IF, Lee MS, Saliba RM et al (2003) Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol 21:4407–4412

    Article  CAS  PubMed  Google Scholar 

  53. Mari MB, Sandmaier BM, Storer BE et al (2004) Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma. Blood 104:3535–3542

    Article  Google Scholar 

  54. Ruan J, Martin P, Shah B et al (2013) Combination biologic therapy without chemotherapy as initial treatment for mantel cell lymphoma: multi-center phase II study of lenalidomide plus rituximab. Blood 21:247

    Google Scholar 

  55. Blum K (2012) A phase i trial of the Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib (PCI-32765), in combination with rituximab (R) and bendamustine in patients with relapsed/refractory non-Hodgkin’s lymphoma (NHL). Blood, p 1643

    Google Scholar 

  56. Kahl BS, Spurgeon, SE, Furman RR et al (2013) Results of a phase I study of idelalisb, a PI3κδ inhibitor with relapsed or refractory mantle cell lymphoma (MCL). Blood Abstract85

    Google Scholar 

  57. Davids MS, Roberts AW, Anderson MA et al (2012) The BCL-2-specific BH3-mimetic ABT-199 (GDC-0199) is active and well-tolerated in patients with relapsed non-hodgkin lymphoma: interim results of a phase I study [abstract]. Blood 120:404

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Arthur G James Comprehensive Cancer Center, The Ohio State University Comprehensive Cancer Center, 320 W 10th Street A350C Starling Loving Hall, Columbus, OH, 43210, USA

    Kami Maddocks & Kristie A. Blum

Authors
  1. Kami Maddocks
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kristie A. Blum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kami Maddocks .

Editor information

Editors and Affiliations

  1. Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts, USA

    Andrew M. Evens

  2. Division of Hematology, Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA

    Kristie A. Blum

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Maddocks, K., Blum, K.A. (2015). Treatment Strategies in Mantle Cell Lymphoma. In: Evens, A., Blum, K. (eds) Non-Hodgkin Lymphoma. Cancer Treatment and Research, vol 165. Springer, Cham. https://doi.org/10.1007/978-3-319-13150-4_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-13150-4_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-13149-8

  • Online ISBN: 978-3-319-13150-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation