Skip to main content
SpringerLink
Log in

Frontline therapy in mantle cell lymphoma: The role of high-dose therapy and integration of new agents

  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Mantle cell lymphoma (MCL) is a unique lymphoma subtype comprising 6% to 8% of new lymphoma diagnoses. It is generally considered to be incurable with standard lymphoma therapies. The median overall survival (OS) is often reported to be 3 to 4 years, but more recent data suggest that the median OS may be longer than 5 years. There is considerable heterogeneity in MCL, with some patients succumbing to their disease in less than a year and others surviving for more than 10 years. The biology of MCL is reasonably well understood, and targeted therapies based on this knowledge are in development. Clinical trials incorporating new agents into standard therapies are under way. The optimal frontline treatment strategy is not defined and is a source of controversy. Intensive therapies administered to younger patients appear to produce better-quality remission than standard treatments, and one randomized clinical trial demonstrates improved OS with an intensive approach. Additional randomized clinical trials defining standard approaches are needed.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The Non-Hodgkin’s Lymphoma Classification Project. Blood 1997, 89:3909–3918.

  2. Herrmann A, Hoster E, Zwingers T, et al.: Improvement of overall survival in advanced stage mantle cell lymphoma. J Clin Oncol 2009, 27:511–518.

    Article  PubMed  Google Scholar 

  3. Kienle D, Katzenberger T, Ott G, et al.: Quantitative gene expression deregulation in mantle-cell lymphoma: correlation with clinical and biologic factors. J Clin Oncol 2007, 25:2770–2777.

    Article  PubMed  CAS  Google Scholar 

  4. Jares P, Colomer D, Campo E: Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics. Nat Rev Cancer 2007, 7:750–762.

    Article  PubMed  CAS  Google Scholar 

  5. Martin P, Coleman M, Leonard JP: Progress in mantle-cell lymphoma. J Clin Oncol 2009, 27:481–483.

    Article  PubMed  Google Scholar 

  6. Rosenwald A, Wright G, Wiestner A, et al.: The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell 2003, 3:185–197.

    Article  PubMed  CAS  Google Scholar 

  7. Hartmann E, Fernandez V, Moreno V, et al.: Five-gene model to predict survival in mantle-cell lymphoma using frozen or formalin-fixed, paraffin-embedded tissue. J Clin Oncol 2008, 26:4966–4972.

    Article  PubMed  Google Scholar 

  8. Determann O, Hoster E, Ott G, et al.: Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group. Blood 2008, 111:2385–2387.

    Article  PubMed  CAS  Google Scholar 

  9. Katzenberger T, Petzoldt C, Höller S, et al.: The Ki67 proliferation index is a quantitative indicator of clinical risk in mantle cell lymphoma. Blood 2006, 107:3407.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  11. Lenz G, Dreyling M, Hoster E, et al.: Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol 2005, 23:1984–1992.

    Article  PubMed  CAS  Google Scholar 

  12. Howard OM, Gribben JG, Neuberg DS, et al.: Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: molecular complete responses are not predictive of progression-free survival. J Clin Oncol 2002, 20:1288–1294.

    Article  PubMed  CAS  Google Scholar 

  13. Romaguera JE, Fayad L, Rodriguez MA, et al.: 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 2005, 23:7013–7023.

    Article  PubMed  CAS  Google Scholar 

  14. Fayad L, Thomas DA, Romaguera J: Update of the M.D. Anderson Cancer Center experience with hyperCVAD and rituximab for the treatment of mantle cell and Burkitttype lymphomas. Clin Lymphoma Myeloma 2007, 8(Suppl 2):S57–S62.

    Article  PubMed  CAS  Google Scholar 

  15. Epner E, Unger JM, Miller TP, et al.: A multi center trial of hyperCVAD + Rituxan in patients with newly diagnosed mantle cell lymphoma [abstract 387]. Blood (ASH Annual Meeting Abstracts) 2007, 110:Abstract 387.

  16. Dreyling M, Hoster E, van Hoof A, et al.: Early consolidation with myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission of mantle cell lymphoma [abstract 769]. Blood (ASH Annual Meeting Abstracts) 2008, 112:285.

    Google Scholar 

  17. Dreyling M, Lenz G, Hoster E, 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, 105:2677–2684.

    Article  PubMed  CAS  Google Scholar 

  18. Geisler CH, Kolstad A, Laurell A, 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, 112:2687–2693.

    Article  PubMed  CAS  Google Scholar 

  19. Delarue R, Haioun C, Ribrag V, et al.: RCHOP and RDHAP followed by autologous stem cell transplantation (ASCT) in mantle cell lymphoma: final results of a phase II study from the GELA [abstract 581]. Blood (ASH Annual Meeting Abstracts) 2008, 112:218.

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  21. Kahl B, Chang J, Eickhoff J, et al.: VcR-CVAD produces a high complete response rate in untreated mantle cell lymphoma: a phase II study from the Wisconsin Oncology Network [abstract 265]. Blood (ASH Annual Meeting Abstracts) 2008, 112:104.

    Google Scholar 

  22. Smith M, Zhang L, Gordon L, et al.: Phase II study of RCHOP followed by 90 Y-ibritumomab tiuxetan in untreated mantle cell lymphoma: Eastern Cooperative Oncology Group Study E1499 [abstract 389]. Blood (ASH Annual Meeting Abstracts) 2007, 110:Abstract 389.

  23. Kahl B, Longo W, Eickhoff J, et al.: Maintenance rituximab following induction chemoimmunotherapy may prolong progression-free survival in mantle cell lymphoma: a pilot study from the Wisconsin Oncology Network. Ann Oncol 2006, 17:1418–1423.

    Article  PubMed  CAS  Google Scholar 

  24. Hess G, Herbrecht R, Romaguera J, et al.: Phase III study to evaluate temsirolimus compared with investigator’s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009, 27:3822–3829.

    Article  PubMed  CAS  Google Scholar 

  25. Reeder C, Gornet M, Habermann T, et al.: A phase II trial of the oral mTOR inhibitor everolimus (RADOO1) in relapsed aggressive non-Hodgkin lymphoma [abstract 121]. Blood (ASH Annual Meeting Abstracts) 2007, 110:Abstract 121.

  26. Zinzani PL, Witzig TE, Vose JM, et al.: Confirmation of the efficacy and safety of lenalidomide oral monotherapy in patients with relapsed or refractory mantle cell lymphoma: results of an international study (NHL-003) [abstract 262]. Blood (ASH Annual Meeting Abstracts) 2008, 112:104.

    Google Scholar 

  27. Rummel M, von Gruenhagen U, Niederle N, et al.: Bendamustine plus rituximab versus CHOP plus rituximab in the first line treatment of patients with follicular, indolent, and mantle cell lymphomas: results of a randomized phase III study of the Study Group Indolent Lymphomas (StiL) [abstract 2596]. Blood (ASH Annual Meeting Abstracts) 2008, 112:900.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, H4/534 CSC, Madison, WI, 53792, USA

    Brad S. Kahl

Authors
  1. Brad S. Kahl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brad S. Kahl.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kahl, B.S. Frontline therapy in mantle cell lymphoma: The role of high-dose therapy and integration of new agents. Curr Hematol Malig Rep 4, 213–217 (2009). https://doi.org/10.1007/s11899-009-0028-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11899-009-0028-z

Keywords

Search

Navigation