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Bendamustine as salvage treatment for patients with relapsed or refractory mantle cell lymphoma patients: a retrospective study of the Spanish experience

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Abstract

Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1–8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3–18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1–54.2). Median overall survival (OS) was 30 months (95 % CI 25.6–34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses (p < 0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses (p < 0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL.

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References

  1. Swerdlow SH, Campo E, Harris N, Jaffe E, Pileri S, Stein H et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. IARC Press, Lyon, France

    Google Scholar 

  2. Howard OM, Gribben JG, Neuberg DS, Grossbard M, Poor C, Janicek MJ et al (2002) Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: molecular complete responses are not predictive of progression-free survival. J Clin Oncol 20(5):1288–1294

    Article  CAS  PubMed  Google Scholar 

  3. Lenz G, Dreyling M, Hoster E, Wörmann B, Dührsen U, Metzner B et al (2005) 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 23(9):1984–1992

    Article  CAS  PubMed  Google Scholar 

  4. Lefrère F, Delmer A, Suzan F, Levy V, Belanger C, Djabarri M et al (2002) Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study. Leukemia 16(4):587–593

    Article  PubMed  Google Scholar 

  5. Romaguera JE, Fayad L, Rodriguez MA, Broglio KR, Hagemeister FB, Pro B 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(28):7013–7023

    Article  CAS  PubMed  Google Scholar 

  6. Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M et al (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 2 multicenter study by the Nordic Lymphoma Group. Blood 112(7):2687–2693

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Hermine O, Hoster E, Walewski J, Ribrag V, Brousse N, Thieblemont C et al. Alternating courses of 3x CHOP and 3x DHAP plus rituximab followed by a high dose ARA-C containing myeloablative regimen and autologous stem cell transplantation (ASCT) increases overall survival when compared to 6 courses of CHOP Plus rituximab followed by myeloablative radiochemotherapy and ASCT in mantle cell lymphoma: final analysis of the MCL Younger Trial of the European Mantle Cell Lymphoma Network (MCL net). American Society of Hematology Annual Meeting. 2012. [Abstract] Dec 120; Atlanta: 151

  8. Zucca E, Roggero E, Pinotti G, Pedrinis E, Capella C, Venco A et al (1995) Patterns of survival in mantle cell lymphoma. Ann Oncol 6(3):257–262

    CAS  PubMed  Google Scholar 

  9. Vandenberghe E, Ruiz de Elvira C, Loberiza FR et al (2003) 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 120(5):793–800

    Article  PubMed  Google Scholar 

  10. 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 

  11. Robinson et al (2006) Reduced-intensity conditioning and allogenic stem cell transplantation in mantle cell lymphoma: an update from the Lymphoid Working Party of the EBMT. Bone Marrow Transplant 37(Suppl 1):236 (a)

    Google Scholar 

  12. 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(18):4144–4152

    Article  CAS  PubMed  Google Scholar 

  13. Gayoso J, Martino R, Balsalobre P et al (2009) (GELTAMO). Long-term results of fludarabine/melphalan as reduced-intensity conditioning regimen in mantle cell lymphoma: age matters. Bone Marrow Transplant 43(Suppl 1):753 (a)

    Google Scholar 

  14. Hess G, Herbrecht R, Romaguera J et al (2009) 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 27(23):3822–3829

    Article  CAS  PubMed  Google Scholar 

  15. 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(30):4867–4874

    Article  PubMed  Google Scholar 

  16. Witzig TE, Vose JM, Zinzani PL et al (2011) An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma. Ann Oncol 22(7):1622–1627

    Article  CAS  PubMed  Google Scholar 

  17. Lamm W, Kaufmann H, Raderer M, Hoffmann M, Chott A, Zielinski C, Drach J (2011) Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma. Haematologica 96(7):1008–1014

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Ansell SM, Tang H, Kurtin PJ, Koenig PA, Inwards DJ, Shah K et al (2011) Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study. Lancet Oncol 12(4):361–368

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Wang M, Fayad L, Wagner-Bartak N, Zhang L, Hagemeister F, Neelapu SS 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(7):716–723

    Article  PubMed  Google Scholar 

  20. Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D 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(15):3383–3389

    Article  CAS  PubMed  Google Scholar 

  21. Robinson KS, Williams ME, van der Jagt RH, Cohen P, Herst JA, Tulpule A et al (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(27):4473–4479

    Article  CAS  PubMed  Google Scholar 

  22. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM et al (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17(4):1244

    CAS  PubMed  Google Scholar 

  23. Damon LE, Johnson JL, Niedzwiecki D, Cheson BD, Hurd DD, Bartlett NL et al (2009) Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol 27(36):6101–6108

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Merli F, Luminari S, Ilariucci F, Petrini M, Visco C, Ambrosetti A et al (2012) 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 156(3):346–353

    Article  CAS  PubMed  Google Scholar 

  25. Geisler CH, Kolstad A, Laurell A, Jerkeman M, Räty R, Andersen NS 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(3):355–362

    Article  CAS  PubMed  Google Scholar 

  26. Gianni AM, Magni M, Martelli M, Di Nicola M, Carlo-Stella C, Pilotti S et al (2003) Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen). Blood 102(2):749–755

    Article  CAS  PubMed  Google Scholar 

  27. Leoni LM, Bailey B, Reifert J, Bendall HH, Zeller RW, Corbeil J et al (2008) Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res 14(1):309–317

    Article  CAS  PubMed  Google Scholar 

  28. Czuczman MS, Lamonica D, Gaylor SK, Bush, Nadolny P et al (2012) Open-Label bendamustine Combined with rituximab for treatment of relapsed/refractory mantle-cell lymphoma: efficacy and safety findings. Blood 120:1632 (a)

    Google Scholar 

  29. Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C et al (2013) 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 381(9873):1203–1210

    Article  CAS  PubMed  Google Scholar 

  30. Rodríguez J, Gutierrez A, Palacios A, Navarrete M, Blancas I, Alarcón J et al (2007) Rituximab, gemcitabine and oxaliplatin: an effective regimen in patients with refractory and relapsing mantle cell lymphoma. Leuk Lymphoma 48(11):2172–2178

    Article  PubMed  Google Scholar 

  31. Rigacci L, Puccini B, Cortelazzo S, Gaidano G, Piccin A, D’Arco A et al (2012) Bendamustine with or without rituximab for the treatment of heavily pretreated non-Hodgkin’s lymphoma patients: a multicenter retrospective study on behalf of the Italian Lymphoma Foundation (FIL). Ann Hematol 91(7):1013–1022

    Article  CAS  PubMed  Google Scholar 

  32. Sanchez-Gonzalez B, Peñalver FJ, Medina A, Guillén H, Calleja M, Gironella M et al (2012) Clinical experience of bendamustine treatment for non-Hodgkin lymphoma and chronic lymphocytic leukemia in Spain. Leuk Res 36(6):709–714

    Article  CAS  PubMed  Google Scholar 

  33. Warsch S, Hosein PJ, Maeda LS, Alizadeh AA, Lossos IS (2012) A retrospective study evaluating the efficacy and safety of bendamustine in the treatment of mantle cell lymphoma. Leuk Lymphoma 53(7):1299–1305

    Article  CAS  PubMed  Google Scholar 

  34. Rummel MJ, Kaiser U, Balser C, Stauch MB, Brugger W, Welslau M et al (2010) Bendamustine plus rituximab versus fludarabine plus rituximab in patients with relapsed follicular, indolent and mantle cell lymphomas: final results of the randomized phase III study NHL 2–2003 on behalf of the StiL (Study Group Indolent Lymphomas, Germany). Blood 116:856 (a)

    Google Scholar 

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Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Hematology, Hospital Universitario La Princesa, 28006, Madrid, Spain

    A. García-Noblejas, J. Cannata-Ortiz & R. Arranz

  2. Department of Hematology, Hospital Quirón, Madrid, Spain

    C. Martínez Chamorro

  3. Department of Hematology, Hospital Universitario Puerta de Hierro, Madrid, Spain

    B. Navarro Matilla

  4. Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain

    C. Da Silva Rodriguez

  5. Department of Hematology, Hospital General Yagüe, Burgos, Spain

    T. J. González-Lopez

  6. Department of Hematology, Hospital MD Anderson, Madrid, Spain

    R. Oña Navarrete

  7. Department of Hematology, Hospital General Jerez, Jerez, Spain

    M. J. Ramírez Sánchez

  8. Department of Hematology, Hospital Universitario Fundación Alcorcón, Madrid, Spain

    P. Martínez Barranco

  9. Department of Oncology, Hospital Morales Meseguer, Murcia, Spain

    J. J. Sánchez Blanco

  10. Department of Hematology, Hospital Central de Asturias, Oviedo, Spain

    C. Nicolás

  11. Department of Hematology, Hospital Gregorio Marañón, Madrid, Spain

    R. Pérez

  12. Department of Hematology, Hospital del Mar, Barcelona, Spain

    B. Sánchez González

  13. Department of Hematology, Hospital Universitario Ramón y Cajal, Madrid, Spain

    A. M. Ruedas López

  14. Department of Hematology, Instituto Clínico de Oncología (ICO), Barcelona, Spain

    E. Domingo-Domenech

  15. Department of Hematology, Clínica Universitaria de Navarra, Navarra, Spain

    C. Panizo

  16. Department of Hematology, Hospital General de Elda, Alicante, Spain

    S. Macia

  17. Department of Hematology, Hospital Rio Hortega, Valladolid, Spain

    E. Fernández-Fonseca

Authors
  1. A. García-Noblejas
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  2. C. Martínez Chamorro
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  3. B. Navarro Matilla
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  4. C. Da Silva Rodriguez
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  6. R. Oña Navarrete
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  7. M. J. Ramírez Sánchez
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  8. P. Martínez Barranco
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  9. J. J. Sánchez Blanco
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  10. C. Nicolás
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  11. R. Pérez
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  13. A. M. Ruedas López
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  14. E. Domingo-Domenech
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  18. J. Cannata-Ortiz
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  19. R. Arranz
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Correspondence to A. García-Noblejas.

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García-Noblejas, A., Martínez Chamorro, C., Navarro Matilla, B. et al. Bendamustine as salvage treatment for patients with relapsed or refractory mantle cell lymphoma patients: a retrospective study of the Spanish experience. Ann Hematol 93, 1551–1558 (2014). https://doi.org/10.1007/s00277-014-2077-1

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