UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Initial treatment of mantle cell lymphoma

Authors
Arnold S Freedman, MD
Jonathan W Friedberg, MD
Section Editor
Andrew Lister, MD, FRCP, FRCPath, FRCR
Deputy Editor
Alan G Rosmarin, MD

INTRODUCTION

Mantle cell lymphoma (MCL), one of the B cell non-Hodgkin lymphomas (NHLs), has a variable course. A minority of patients with this disorder may survive untreated for many years. However, in more patients, MCL assumes a more virulent character, akin to that of an aggressive NHL variant.

The initial treatment of MCL will be discussed here. Clinical and pathologic features, diagnosis, and differential diagnosis of this disorder are discussed separately, as is the treatment of relapsed or refractory MCL. (See "Clinical manifestations, pathologic features, and diagnosis of mantle cell lymphoma" and "Treatment of relapsed or refractory mantle cell lymphoma".)

ONCOLOGIC EMERGENCIES

Oncologic emergencies and treatment-related hematologic toxicities are common in the aggressive NHLs. Clinicians must always be alert to their potential presence, and be prepared to deal with them urgently and effectively. (See "Clinical presentation and diagnosis of non-Hodgkin lymphoma", section on 'Oncologic emergencies'.)

Emergencies that are more common in patients with MCL include hyperleukocytosis and intestinal obstruction or intussusception:

Involvement of the gastrointestinal tract is common in MCL, occasionally presenting with multiple intestinal polyposis and intestinal obstruction or intussusception. (See "Epidemiology, clinical features, and diagnosis of mechanical small bowel obstruction in adults" and "Clinical presentation and diagnosis of primary gastrointestinal lymphomas".)

                 

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Thu Sep 08 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Yoong Y, Kurtin PJ, Allmer C, et al. Efficacy of splenectomy for patients with mantle cell non-Hodgkin's lymphoma. Leuk Lymphoma 2001; 42:1235.
  2. Angelopoulou MK, Siakantariz MP, Vassilakopoulos TP, et al. The splenic form of mantle cell lymphoma. Eur J Haematol 2002; 68:12.
  3. Ruchlemer R, Wotherspoon AC, Thompson JN, et al. Splenectomy in mantle cell lymphoma with leukaemia: a comparison with chronic lymphocytic leukaemia. Br J Haematol 2002; 118:952.
  4. Orchard J, Garand R, Davis Z, et al. A subset of t(11;14) lymphoma with mantle cell features displays mutated IgVH genes and includes patients with good prognosis, nonnodal disease. Blood 2003; 101:4975.
  5. Martin P, Chadburn A, Christos P, et al. Outcome of deferred initial therapy in mantle-cell lymphoma. J Clin Oncol 2009; 27:1209.
  6. 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.
  7. Goswami RS, Atenafu EG, Xuan Y, et al. MicroRNA signature obtained from the comparison of aggressive with indolent non-Hodgkin lymphomas: potential prognostic value in mantle-cell lymphoma. J Clin Oncol 2013; 31:2903.
  8. Hoster E, Rosenwald A, Berger F, et al. Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network. J Clin Oncol 2016; 34:1386.
  9. Navarro A, Clot G, Royo C, et al. Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biologic and clinical features. Cancer Res 2012; 72:5307.
  10. Xu W, Li JY. SOX11 expression in mantle cell lymphoma. Leuk Lymphoma 2010; 51:1962.
  11. Fernàndez V, Salamero O, Espinet B, et al. Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma. Cancer Res 2010; 70:1408.
  12. 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.
  13. Schulz H, Bohlius JF, Trelle S, et al. Immunochemotherapy with rituximab and overall survival in patients with indolent or mantle cell lymphoma: a systematic review and meta-analysis. J Natl Cancer Inst 2007; 99:706.
  14. Fenske TS, Zhang MJ, Carreras J, et al. Autologous or reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chemotherapy-sensitive mantle-cell lymphoma: analysis of transplantation timing and modality. J Clin Oncol 2014; 32:273.
  15. Abrahamsson A, Albertsson-Lindblad A, Brown PN, et al. Real world data on primary treatment for mantle cell lymphoma: a Nordic Lymphoma Group observational study. Blood 2014; 124:1288.
  16. Martin P, Chadburn A, Christos P, et al. Intensive treatment strategies may not provide superior outcomes in mantle cell lymphoma: overall survival exceeding 7 years with standard therapies. Ann Oncol 2008; 19:1327.
  17. Foran JM, Rohatiner AZ, Cunningham D, et al. 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 2000; 18:317.
  18. Ghielmini M, Schmitz SF, Cogliatti S, et al. 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 2005; 23:705.
  19. 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.
  20. Khouri IF, Romaguera J, Kantarjian H, et al. Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma. J Clin Oncol 1998; 16:3803.
  21. 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.
  22. Herold M, Haas A, Doerken B, et al. Immunochemotherapy (R-MCP) in advanced mantle cell lymphoma is not superior to chemotherapy (MCP) alone - 50 months up date of the OSHO phasae III study (abstract). Ann Oncol 2008; 19(suppl 4):12.
  23. Forstpointner R, Dreyling M, Repp R, et al. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2004; 104:3064.
  24. Andersen NS, Pedersen LB, Laurell A, et al. Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma. J Clin Oncol 2009; 27:4365.
  25. Schulz H, Bohlius J, Skoetz N, et al. Chemotherapy plus Rituximab versus chemotherapy alone for B-cell non-Hodgkin's lymphoma. Cochrane Database Syst Rev 2007; :CD003805.
  26. Griffiths R, Mikhael J, Gleeson M, et al. Addition of rituximab to chemotherapy alone as first-line therapy improves overall survival in elderly patients with mantle cell lymphoma. Blood 2011; 118:4808.
  27. Meusers P, Engelhard M, Bartels H, et al. Multicentre randomized therapeutic trial for advanced centrocytic lymphoma: anthracycline does not improve the prognosis. Hematol Oncol 1989; 7:365.
  28. Nickenig C, Dreyling M, Hoster E, et al. Combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) improves response rates but not survival and has lower hematologic toxicity compared with combined mitoxantrone, chlorambucil, and prednisone (MCP) in follicular and mantle cell lymphomas: results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group. Cancer 2006; 107:1014.
  29. Hoster E, Klapper W, Hermine O, et al. Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network. J Clin Oncol 2014; 32:1338.
  30. Rummel MJ, Niederle N, Maschmeyer G, 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; 381:1203.
  31. Flinn IW, van der Jagt R, Kahl BS, et al. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood 2014; 123:2944.
  32. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021602s040lbl.pdf (Accessed on October 13, 2014).
  33. Robak T, Huang H, Jin J, et al. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med 2015; 372:944.
  34. Kluin-Nelemans HC, Hoster E, Hermine O, et al. Treatment of older patients with mantle-cell lymphoma. N Engl J Med 2012; 367:520.
  35. Ruan J, Martin P, Furman RR, et al. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol 2011; 29:690.
  36. Furtado M, Johnson R, Kruger A, et al. Addition of bortezomib to standard dose chop chemotherapy improves response and survival in relapsed mantle cell lymphoma. Br J Haematol 2015; 168:55.
  37. Hermine O, Hoster E, Walewski J, 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; 388:565.
  38. 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.
  39. Geisler CH, Kolstad A, Laurell A, et al. 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 2012; 158:355.
  40. Damon LE, Johnson JL, Niedzwiecki D, et al. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol 2009; 27:6101.
  41. Schaffel R, Hedvat CV, Teruya-Feldstein J, et al. Prognostic impact of proliferative index determined by quantitative image analysis and the International Prognostic Index in patients with mantle cell lymphoma. Ann Oncol 2010; 21:133.
  42. Teodorovic I, Pittaluga S, Kluin-Nelemans JC, et al. Efficacy of four different regimens in 64 mantle-cell lymphoma cases: clinicopathologic comparison with 498 other non-Hodgkin's lymphoma subtypes. European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol 1995; 13:2819.
  43. Visco C, Finotto S, Zambello R, et al. Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. J Clin Oncol 2013; 31:1442.
  44. Zucca E, Roggero E, Pinotti G, et al. Patterns of survival in mantle cell lymphoma. Ann Oncol 1995; 6:257.
  45. Eve HE, Seymour JF, Rule SA. Impairment of peripheral blood stem-cell mobilisation in patients with mantle-cell lymphoma following primary treatment with fludarabine and cyclophosphamide +/- rituximab. Leuk Lymphoma 2009; 50:463.
  46. Ganti AK, Bierman PJ, Lynch JC, et al. Hematopoietic stem cell transplantation in mantle cell lymphoma. Ann Oncol 2005; 16:618.
  47. Sweetenham JW. Stem cell transplantation for mantle cell lymphoma: should it ever be used outside clinical trials? Bone Marrow Transplant 2001; 28:813.
  48. Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol 1999; 17:1244.
  49. Khouri IF, Saliba RM, Okoroji GJ, et al. Long-term follow-up of autologous stem cell transplantation in patients with diffuse mantle cell lymphoma in first disease remission: the prognostic value of beta2-microglobulin and the tumor score. Cancer 2003; 98:2630.
  50. Till BG, Gooley TA, Crawford N, et al. Effect of remission status and induction chemotherapy regimen on outcome of autologous stem cell transplantation for mantle cell lymphoma. Leuk Lymphoma 2008; 49:1062.
  51. Romaguera JE, Fayad LE, Feng L, et al. Ten-year follow-up after intense chemoimmunotherapy with Rituximab-HyperCVAD alternating with Rituximab-high dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma. Br J Haematol 2010; 150:200.
  52. Merli F, Luminari S, Ilariucci F, et al. Rituximab plus HyperCVAD alternating with high dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma, a multicentre trial from Gruppo Italiano Studio Linfomi. Br J Haematol 2012; 156:346.
  53. Bernstein SH, Epner E, Unger JM, et al. A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213. Ann Oncol 2013; 24:1587.
  54. Chang JE, Peterson C, Choi S, et al. VcR-CVAD induction chemotherapy followed by maintenance rituximab in mantle cell lymphoma: a Wisconsin Oncology Network study. Br J Haematol 2011; 155:190.
  55. Chang JE, Li H, Smith MR, et al. Phase 2 study of VcR-CVAD with maintenance rituximab for untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group study (E1405). Blood 2014; 123:1665.
  56. Epner E, Unger JM, Miller TP, et al. A multi center trial of hyperCVAD + rituxan in patients with nely diagnosed mantle cell lymphoma (abstract). Blood 2007; 110:387.
  57. LaCasce AS, Vandergrift JL, Rodriguez MA, et al. Comparative outcome of initial therapy for younger patients with mantle cell lymphoma: an analysis from the NCCN NHL Database. Blood 2012; 119:2093.
  58. Hosein PJ, Pastorini VH, Paes FM, et al. Utility of positron emission tomography scans in mantle cell lymphoma. Am J Hematol 2011; 86:841.
  59. Mato AR, Svoboda J, Feldman T, et al. Post-treatment (not interim) positron emission tomography-computed tomography scan status is highly predictive of outcome in mantle cell lymphoma patients treated with R-HyperCVAD. Cancer 2012; 118:3565.
  60. Seam P, Juweid ME, Cheson BD. The role of FDG-PET scans in patients with lymphoma. Blood 2007; 110:3507.
  61. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
  62. Ketterer N, Salles G, Espinouse D, et al. Intensive therapy with peripheral stem cell transplantation in 16 patients with mantle cell lymphoma. Ann Oncol 1997; 8:701.
  63. Freedman AS, Neuberg D, Gribben JG, et al. High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission. J Clin Oncol 1998; 16:13.
  64. 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.
  65. Murali S, Winton E, Waller EK, et al. Long-term progression-free survival after early autologous transplantation for mantle-cell lymphoma. Bone Marrow Transplant 2008; 42:529.
  66. 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.
  67. Evens AM, Winter JN, Hou N, et al. A phase II clinical trial of intensive chemotherapy followed by consolidative stem cell transplant: long-term follow-up in newly diagnosed mantle cell lymphoma. Br J Haematol 2008; 140:385.
  68. 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.
  69. van 't Veer MB, de Jong D, MacKenzie M, et al. High-dose Ara-C and beam with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. Br J Haematol 2009; 144:524.
  70. Kolstad A, Laurell A, Jerkeman M, et al. Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma. Blood 2014; 123:2953.
  71. Armand P, Redd R, Bsat J, et al. A phase 2 study of Rituximab-Bendamustine and Rituximab-Cytarabine for transplant-eligible patients with mantle cell lymphoma. Br J Haematol 2016; 173:89.
  72. Budde LE, Guthrie KA, Till BG, et al. Mantle cell lymphoma international prognostic index but not pretransplantation induction regimen predicts survival for patients with mantle-cell lymphoma receiving high-dose therapy and autologous stem-cell transplantation. J Clin Oncol 2011; 29:3023.
  73. Magni M, Di Nicola M, Devizzi L, et al. Successful in vivo purging of CD34-containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion. Blood 2000; 96:864.
  74. Mangel J, Buckstein R, Imrie K, et al. Immunotherapy with rituximab following high-dose therapy and autologous stem-cell transplantation for mantle cell lymphoma. Semin Oncol 2002; 29:56.
  75. Thieblemont C, Antal D, Lacotte-Thierry L, et al. Chemotherapy with rituximab followed by high-dose therapy and autologous stem cell transplantation in patients with mantle cell lymphoma. Cancer 2005; 104:1434.
  76. 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.
  77. Rummel MJ, Knauf W, Goerner M, 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). (abstract 7503). J Clin Oncol 2016; 34.
  78. Kenkre VP, Long WL, Eickhoff JC, et al. Maintenance rituximab following induction chemo-immunotherapy for mantle cell lymphoma: long-term follow-up of a pilot study from the Wisconsin Oncology Network. Leuk Lymphoma 2011; 52:1675.
  79. Ahmadi T, McQuade J, Porter D, et al. Potential prolongation of PFS in mantle cell lymphoma after R-HyperCVAD: auto-SCT consolidation or rituximab maintenance. Bone Marrow Transplant 2012; 47:1082.
  80. Ruan J, Martin P, Shah B, et al. Lenalidomide plus Rituximab as Initial Treatment for Mantle-Cell Lymphoma. N Engl J Med 2015; 373:1835.