Skip to main content

Advertisement

SpringerLink
Log in

Current treatment strategy and new agents in mantle cell lymphoma

  • Progress in Hematology
  • Targeted treatment and new agents in malignant lymphoma
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Mantle cell lymphoma (MCL) is a well-recognized lymphoma subtype that accounts for about 5% of all patients with non-Hodgkin lymphoma. The clinical course of MCL ranges from an indolent disease to a rapidly progressive malignancy, with a poor prognosis and a median overall survival (OS) of about 3–5 years reported in earlier data sets. Knowledge of its biology has increased in the last few years. Unfortunately, this progress has not yet brought any major improvements in therapeutic approaches, which still remain highly unsatisfactory. Recent improvement has been achieved by the successful introduction of monoclonal antibodies and dose-intensified approaches including autologous stem cell transplantation strategies. However, with the exception of allogeneic hematopoietic stem cell transplantation, current treatment approaches are non-curative, and the corresponding survival curves are characterized by a delayed but continuous decline and a median survival of 4–6 years. In recent years, new insights into the biology of MCL have been obtained which have provided the rationale for the development of novel therapeutic strategies. Emerging new drugs such as bendamustine, proteasome inhibitors, antibodies, mTOR inhibitors, and immunomodulatory drugs and others are based on the dysregulated control of cell cycle machinery and impaired apoptotic pathways. The efficacy of these agents as monotherapy was demonstrated to be comparable to conventional chemotherapy in relapsed MCL, and combination strategies are currently being investigated in clinical trials.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Schmidt C, Dreyling M. Therapy of mantle cell lymphoma: current standards and future strategies. Hematol Oncol Clin North Am. 2008;22:953–63.

    Article  PubMed  Google Scholar 

  2. Fisher RI, Dahlberg S, Nathwani BN, et al. A clinical analysis of two indolent lymphoma entities: mantle cell lymphoma and marginal zone lymphoma (including the mucosa-associated lymphoid tissue and monocytoid B-cell subcategories): a Southwest Oncology Group study. Blood. 1995;85:1075–82.

    CAS  PubMed  Google Scholar 

  3. Yatabe Y, Suzuki R, Tobinai K, et al. Significance of cyclin D1 overexpression for the diagnosis of mantle cell lymphoma: a clinicopathologic comparison of cyclin D1-positive MCL and cyclin D1-negative MCL-like B-cell lymphoma. Blood. 2000;95:2253–61.

    CAS  PubMed  Google Scholar 

  4. Tam CS, Bassett R, Ledesma C, et al. Mature results of the M.D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma. Blood. 2009;113:4144–52.

    Article  CAS  PubMed  Google Scholar 

  5. 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;112:2687–93.

    Article  CAS  PubMed  Google Scholar 

  6. Hiddemann W, Lenz G, Weisenburger DD, et al. Mantle cell lymphoma. In: Mauch PM, Armitage J, Coiffier B, et al., editors. Non-Hodgkin’s lymphomas. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 461–76.

  7. 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;20:1288–94.

    Article  CAS  PubMed  Google Scholar 

  8. 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;23:1984–92.

    Article  CAS  PubMed  Google Scholar 

  9. Dreyling M, Meyer T, Hiddemann W. Mantle cell lymphoma. In: Cavalli F, Armitage JO, Longo DL, editors. Annual of lymphoid malignancies. London: Martin Dunitz; 2001. p. 61–8.

  10. Vandenberghe E, Ruiz de Elvira C, Loberiza FR, et al. Outcome of autologous transplantation for mantle cell lymphoma: a study by the European Blood and Bone Marrow Transplant and Autologous Blood and Marrow Transplant Registries. Br J Haematol. 2003;120:793–800.

    Article  PubMed  Google Scholar 

  11. Gianni AM, Magni M, Martelli M, et al. Long-term remission in mantle-cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen). Blood. 2003;102:749–55.

    Article  CAS  PubMed  Google Scholar 

  12. Ogura M, Kagami Y, Taji H, et al. Phase I/II study of new salvage therapy (CHASE) for refractory or relapsed malignant lymphomas. Int J Hematol. 2003;77:503–11.

    Article  CAS  PubMed  Google Scholar 

  13. Oki Y, Ogura M, Kato H, et al. Phase II study of a salvage regimen using cyclophosphamide, high-dose cytarabine, dexamethasone, etoposide, and rituximab in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Cancer Sci. 2008;99:179–84.

    CAS  PubMed  Google Scholar 

  14. 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;23:7013–23.

    Article  CAS  PubMed  Google Scholar 

  15. Epner EM, Unger J, Miller T, et al. A multi center trial of hyperCVAD + Rituxan in patients with newly diagnosed cell lymphoma. Blood. 2007;110:387.

    Google Scholar 

  16. Mangel J, Leitch HA, Connors JM, et al. Intensive chemotherapy and autologous stem-cell transplantation plus rituximab is superior to conventional chemotherapy for newly diagnosed advanced stage mantle-cell lymphoma: a matched pair analysis. Ann Oncol. 2004;15:283–90.

    Article  CAS  PubMed  Google Scholar 

  17. Corradini P, Ladetto M, Zallio F, et al. Long-term follow-up of indolent lymphoma patients treated with high-dose sequential chemotherapy and autografting: evidence that durable molecular and clinical remission frequently can be attained only in follicular subtypes. J Clin Oncol. 2004;22:1460–8.

    Article  PubMed  Google Scholar 

  18. Khouri IF, Lee MS, Saliba RM, et al. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol. 2003;21:4407–12.

    Article  CAS  PubMed  Google Scholar 

  19. Wang M, Oki Y, Pro B, et al. Phase II study of yttrium-90-ibritumomab tiuxetan in patients with relapsed or refractory mantle cell lymphoma. Clin Oncol. 2009;27:5213–8.

    Article  CAS  Google Scholar 

  20. Gopal AK, Rajendran JG, Petersdorf SH, et al. High-dose chemo-radioimmunotherapy with autologous stem cell support for relapsed mantle cell lymphoma. Blood. 2002;99:3158–62.

    Article  CAS  PubMed  Google Scholar 

  21. Smith MR, Zhang L, Gordon LI, et al. Phase II study of R-CHOP followed by 90Y-ibritumomab tiuxetan in untreated mantle cell lymphoma: Eastern Cooperative Oncology Group study E1499. Blood. 2007;110:389.

    Google Scholar 

  22. Strumberg D, Harstrick A, Doll K, Hoffmann B, Seeber S. Bendamustine hydrochloride activity against doxorubicin-resistant human breast carcinoma cell lines. Anticancer Drugs. 1996;7:415–21.

    Article  CAS  PubMed  Google Scholar 

  23. Niemeyer CC, Bailey B, Riefert J. SDX-105 (bendamustine is a clinically active chemotherapeutic agent with a distinct mechanism of action. Proc Am Assoc Cancer Res. 2004;45:1129.

    Google Scholar 

  24. Leoni LM, Bailey B, Reifert J, et al. Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res. 2008;14:309–17.

    Article  CAS  PubMed  Google Scholar 

  25. Heider A, Niederle N. Efficacy and toxicity of bendamustine in patients with relapsed low-grade non-Hodgkin’s lymphomas. Anticancer Drugs. 2001;12:725–9.

    Article  CAS  PubMed  Google Scholar 

  26. Friedberg JW, Cohen P, Chen L, et al. Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin’s lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol. 2008;26:204–10.

    Article  CAS  PubMed  Google Scholar 

  27. Kahl B, Carbone PP, Bartlett N, Leonard J, Chen L. Bendamustine is effective therapy in patients with rituximab-refractory indolent B-cell non-Hodgkin’s lymphoma: results from a multicenter study. Cancer. 2010;116:106–14.

    CAS  PubMed  Google Scholar 

  28. Bremer K. High rates of long-lasting remissions after 5-day bendamustine chemotherapy cycles in pre-treated low-grade non-Hodgkin’s-lymphomas. J Cancer Res Clin Oncol. 2002;128:603–9.

    Article  CAS  PubMed  Google Scholar 

  29. Robinson KS, Williams ME, van der Jagt RH, et al. 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. 2008;26:4473–9.

    Article  CAS  PubMed  Google Scholar 

  30. Rummel MJ, Niederle N, Maschmeyer G, Banat A, Von Gruenhagen U. Bendamustine plus rituximab is superior in respect of progression free survival and CR rate when compared to CHOP plus rituximab as first-line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas: final results of a randomized phase III study of the Stil (Study Group Indolent Lymphomas, Germany). Blood. 2009;114:405.

    Google Scholar 

  31. Ogura M, Uchida T, Ando K, et al. Multicenter phase II study of bendamustine in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (B-NHL) and mantle cell lymphoma (MCL). Blood. 2009;114:3694.

    Google Scholar 

  32. Nencioni A, Grünebach F, Patrone F, et al. Proteasome inhibitors: antitumor effects and beyond. Leukemia. 2007;21:30–6.

    Article  CAS  PubMed  Google Scholar 

  33. Mani A, Gelmann EP. The ubiquitin-proteasome pathway and its role in cancer. J Clin Oncol. 2005;23:4776–89.

    Article  CAS  PubMed  Google Scholar 

  34. Nakayama KI, Nakayama K. Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer. 2006;6:369–81.

    Article  CAS  PubMed  Google Scholar 

  35. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348:2609–17.

    Article  CAS  PubMed  Google Scholar 

  36. Kane RC, Dagher R, Farrell A, et al. Bortezomib for the treatment of mantle cell lymphoma. Clin Cancer Res. 2007;13:5291–4.

    Article  CAS  PubMed  Google Scholar 

  37. Vignot S, Faivre S, Aguirre D, et al. mTOR-targeted therapy of cancer with rapamycin derivatives. Ann Oncol. 2005;16:525–37.

    Article  CAS  PubMed  Google Scholar 

  38. Witzig TE. Current treatment approaches for mantle-cell lymphoma. J Clin Oncol. 2005;23:6409–14.

    Article  CAS  PubMed  Google Scholar 

  39. Bertoni F, Zucca E, Cotter FE. Molecular basis of mantle cell lymphoma. Br J Haematol. 2004;124:130–40.

    Article  CAS  PubMed  Google Scholar 

  40. Kurtin PJ. Mantle cell lymphoma. Adv Anat Pathol. 1998;5:376–98.

    Article  CAS  PubMed  Google Scholar 

  41. Kurtin PJ, Hobdaz KS, Yiesmer S, et al. Demonstration of distinct antigenic profiles of small B-cell lymphomas by paraffin section immunohistochemistry. Am J Pathol. 1999;112:319–29.

    CAS  Google Scholar 

  42. Witzig TE, Geyer SM, Ghobrial I, et al. Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol. 2005;23:5347–56.

    Article  CAS  PubMed  Google Scholar 

  43. Hess G, Romaguera J, Verhoef G, et al. Phase 3 study of patients with relapsed, refractory mantle cell lymphoma treated with Temsirolimus compared with investigator’s choice therapy. J Clin Oncol. 2009;27:3822–9.

    Article  CAS  PubMed  Google Scholar 

  44. Crocker PR, Varki A. Siglecs, sialic acids and innate immunity. Trends Immunol. 2001;22:337–42.

    Article  CAS  PubMed  Google Scholar 

  45. Hanna R, Ong GL, Mattes MJ. Processing of antibodies bound to B-cell lymphomas and other hematological malignancies. Cancer Res. 1996;56:3062–8.

    CAS  PubMed  Google Scholar 

  46. DiJoseph JF, Armellino DC, Boghaert ER, et al. Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood. 2004;103:1807–14.

    Article  CAS  PubMed  Google Scholar 

  47. Advani A, Coiffier B, Czuczman MS, et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin’s lymphoma: results of a phase I study. J Clin Oncol. 2010;28:2085–93.

    Article  CAS  PubMed  Google Scholar 

  48. Mack M, Riethmueller G, Kufer P. A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity. Proc Natl Acad Sci USA. 1995;92:7021–5.

    Article  CAS  PubMed  Google Scholar 

  49. Brandl C, Haas C, d’Argouges S, et al. The effect of dexamethasone on polyclonal T cell activation and redirected target cell lysis as induced by a CD19/CD3-bispecific single-chain antibody construct. Cancer Immunol Immunother. 2007;56:1551–63.

    Article  CAS  PubMed  Google Scholar 

  50. Bargou R, Leo E, Zugmaier G, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science. 2008;321:974–7.

    Article  CAS  PubMed  Google Scholar 

  51. Kaufmann H, Raderer M, Wohrer S, et al. Antitumor activity of Rituximab plus thalidomide in patients with relapsed/refractory mantle cell lymphoma. Blood. 2004;104:2269–71.

    Article  CAS  PubMed  Google Scholar 

  52. Habermann TM, Lossos IS, Justice G, et al. Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. Br J Haematol. 2009;145:344–9.

    Article  CAS  PubMed  Google Scholar 

  53. Zinzani PL, Witzig T, Vose JM. Efficacy and safety of lenalidomide oral monotherapy in patients with relapsed or refractory mantle cell lymphoma: results of an international study (NHL-003). Blood. 2008;112:262.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, 2-9, Myokencho, Showaku, Nagoya, 466-8650, Japan

    Michinori Ogura

Authors
  1. Michinori Ogura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michinori Ogura.

About this article

Cite this article

Ogura, M. Current treatment strategy and new agents in mantle cell lymphoma. Int J Hematol 92, 25–32 (2010). https://doi.org/10.1007/s12185-010-0607-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-010-0607-8

Keywords

Search

Navigation