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Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment of patients with newly diagnosed/untreated multiple myeloma

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Introduction

Bortezomib is a proteasome inhibitor that has shown important clinical efficacy either as a single agent or in combination in patients with multiple myeloma (MM). In the present protocol, bortezomib was combined with bendamustine and prednisone, in order to assess the efficacy and safety of this combination therapy in patients with newly diagnosed/untreated MM.

Methods

Between June 2006 and October 2013, 49 patients with newly diagnosed/untreated MM were treated with bendamustine 60 mg/m2 on days 1 and 2, bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11, and prednisone 100 mg on days 1, 2, 4, 8 and 11 bendamustine, prednisone and bortezomib (BPV) once every 21 days. Patients were divided into three groups: group A (n = 19) consisted of patients with normal renal function or mild dysfunction (eGFR ≥60 ml/min), group B (n = 15) patients with moderate or severe renal dysfunction (eGFR 15–59 ml/min) and group C (n = 15) patients with renal failure/dialysis (eGFR <15 ml/min).

Results

A median number of two (range 1–5) BPV treatment cycles were given to the patients. The majority of the patients (n = 40, 82 %) responded after at least one cycle of BPV therapy with five stringent complete responses (CRs), nine near complete responses, 12 very good partial responses and 14 partial responses. Five patients had MR, three stable and one progressive disease. After a median observation time of 13 months, progression-free survival (PFS) and overall survival (OS) at 12 months were 92 and 94 %, respectively, for patients with normal renal function or mild renal dysfunction (group A) and 83 and 93 %, respectively, for patients with moderate or severe renal dysfunction (group B). Outcome for these patients was slightly better but not statistically significantly better than that for patients with renal failure/dialysis (group C), who had a PFS, and OS of 66 % (p = 0.08) and 73 % (p = 0.05), respectively.

Summary

These results indicate that this BPV combination is feasible, effective and well tolerated in patients with newly diagnosed MM and normal or impaired renal function.

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References

  • Alexanian R, Dimopoulos M (1994) The treatment of multiple myeloma. N Engl J Med 330:484–489

    Article  PubMed  CAS  Google Scholar 

  • Alexanian R, Barlogie B, Dixon D (1990) Renal failure in multiple myeloma. Pathogenesis and prognostic implications. Arch Intern Med 150:1693–1695

    Article  PubMed  CAS  Google Scholar 

  • Berdeja JG, Savona MR, Chu L, Essell J, Murphy P, Bauer T, Raefsky E, Boccia RV, Flinn IW (2013) Bendamustine, bortezomib and dexamethasone (BBD) as first-line treatment of patients (pts) with multiple myeloma who are not candidates for high dose chemotherapy: toxicity comparison of two dose schedules. Blood (Abstract) 122:3193

    Google Scholar 

  • Berenson JR, Yellin O, Bessudo A, Boccia RV, Noga SJ, Gravenor DS, Patel-Donnelly D, Siegel RS, Kewalramani T, Gorak EJ, Nassir Y, Swift RA, Mayo D (2013) Phase I/II trial assessing bendamustine plus bortezomib combination therapy for the treatment of patients with relapsed or refractory multiple myeloma. Br J Haematol 160:321–330

    Article  PubMed  CAS  Google Scholar 

  • Dimopoulos MA, Kastritis E, Rosinol L, Blade J, Ludwig H (2008) Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia 22:1485–1493

    Article  PubMed  CAS  Google Scholar 

  • Dimopoulos MA, Roussou M, Gavriatopoulou M (2009a) Reversibility of renal impairment in patients with multiple myeloma treated with bortezomib based regimes: identification of predictive factors. Clin Lymphoma Myeloma 9:302–306

    Article  PubMed  CAS  Google Scholar 

  • Dimopoulos MA, Richardson PG, Schlag R, Khuageva NK, Shpilberg O, Kastritis E, Kropff M, Petrucci MT, Delforge M, Alexeeva J, Schots R, Masszi T, Mateos MV, Deraedt W, Liu K, Cakana A, van de Velde H, San Miguel JF (2009b) VMP (bortezomib, melphalan, and prednisone) is active and well tolerated in newly diagnosed patients with multiple myeloma with moderately impaired renal function, and results in reversal of renal impairment: cohort analysis of the phase III VISTA study. J Clin Oncol 27:6086–6093

    Article  PubMed  CAS  Google Scholar 

  • Dimopoulos MA, Terpos E, Chanan-Khan A, Leung N, Ludwig H, Jagannath S, Niesvizky R, Giralt S, Fermand J-P, Blade J, Comenzo RL, Sezer O, Palumbo A, Harousseau J-L, Richardson PG, Barlogie B, Anderson KC, Sonneveld P, Tosi P, Gavo M, Rajkumar SV, Durie BGM, Miguel JS (2010) Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the international myeloma working group. J Clin Oncol 28:4976–4984

    Article  PubMed  Google Scholar 

  • Durie BG, Salmon SE (1975) A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 36:842–854

    Article  PubMed  CAS  Google Scholar 

  • Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV, International Myeloma Working Group (2006) International uniform response criteria for multiple myeloma. Leukemia 20:1467–1473

    Article  PubMed  CAS  Google Scholar 

  • Einsele H, Liebisch P, Langer C, Kropff M, Wandt H, Jung W, Kröger N, Engelhardt M, Ostermann H, Mügge L-O, Wolf H–H, Hart C, Metzner B, Kaufmann M, Gramatzki M, Hertenstein B, Fischer Th, Weisel K, Dölken G, Brugger W, Gollasch H, Maschmeyer G, Pfreundschuh M, Schmitz N, Sezer O, Heidemann E, Jäger E, Kahl C, Kiani A, Dechow T, Rösler W, Simon JP, Dürk H, Pflüger KH, Bentz M, Hess G, Mergenthaler HG, Straka C, Hempel D, Salwender HJ, Fingerle-Rowson G, Knop S (2009) Velcade, intravenous cyclophosphamide and dexamethasone (VCD) Induction for previously untreated multiple myeloma (German DSMM XIa Trial. Blood (ASH Annual Meeting Abstracts) 114:131

    Google Scholar 

  • Ferlay J, Bray F, Pisani P, Parkin DM (2004) GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. IARC Cancer base No 5 Version 2.0. IARC Press, Lyon

  • Fischer K, Cramer P, Busch R, Stilgenbauer S, Bahlo J, Schweighofer CD, Böttcher S, Staib P, Kiehl M, Eckart MJ, Kranz G, Goede V, Elter T, Bühler A, Winkler D, Kneba M, Döhner H, Eichhorst BF, Hallek M, Wendtner CM (2011) Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German chronic lymphocytic leukemia study group. J Clin Oncol 29:3559–3566

    Article  PubMed  CAS  Google Scholar 

  • Gandhi V (2002) Metabolism and mechanisms of action of bendamustine: rationales for combination therapies. Semin Oncol 29(Suppl. 13):4–11

    Article  PubMed  CAS  Google Scholar 

  • Herold M, Schulze A, Niederwieser D, Franke A, Fricke HJ, Richter P, Freund M, Ismer B, Dachselt K, Boewer C, Schirmer V, Weniger J, Pasold R, Winkelmann C, Klinkenstein C, Schulze M, Arzberger H, Bremer K, Hahnfeld S, Schwarzer A, Muller C, Muller C (2006) Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin’s lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO # 19). J Cancer Res Clin Oncol 132:105–112

    Article  PubMed  CAS  Google Scholar 

  • Kastritis E, Anagnostopoulos A, Roussou M, Gika D, Matsouka C, Barmparousi D, Grapsa I, Psimenou E, Bamias A, Dimopoulos MA (2007) Reversibility of renal failure in newly diagnosed multiple myeloma patients treated with high dose dexamethasone-containing regimens and the impact of novel agents. Haematologica 92:546–549

    Article  PubMed  CAS  Google Scholar 

  • Knauf WU, Lissichkov T, Aldaoud A, Liberati A, Loscertales J, Herbrecht R, Juliusson G, Postner G, Gercheva L, Goranov S, Becker M, Fricke HJ, Huguet F, Del Giudice I, Klein P, Tremmel L, Merkle K, Montillo M (2009) Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol 27(26):4378–4384

    Article  PubMed  CAS  Google Scholar 

  • Knop S, Straka C, Haen M, Schwedes R, Hebart H, Einsele H (2005) The efficacy and toxicity of bendamustine in recurrent multiple myeloma after high-dose chemotherapy. Haematologica 90:1287–1288

    PubMed  CAS  Google Scholar 

  • Krebs in Deutschland 2009/2010. 9. Ausgabe. Robert Koch-Institut (Hrsg) und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. Berlin (2013), 120–123

  • Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Rusell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA (2008) Improved survival in multiple myeloma and the impact of novel therapies. Blood 111:2516–2520

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, Fonseca R, Rajkumar SV, Offord JR, Larson DR, Plevak ME, Therneau TM, Greipp PR (2003) Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 78:21–33

    Article  PubMed  Google Scholar 

  • Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med 130:461–470

    Article  PubMed  CAS  Google Scholar 

  • Ludwig H, Kasparu H, Leitgeb C, Rauch E, Linkesch W, Zojer N, Greil R, Seebacher A, Pour L, Weissmann A, Adam Z (2014) Bendamustine-Bortezomib-Dexamethasone (BBD) is an active and well tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood 123:985–991

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Mateos M-V, Oriol A, Rosinol L, de Arriba F, Martin J, Martinez-Lopez J, Echeveste MA, Sarra J, Ramirez G, Ocio EM, Martinez R, Palomera L, Payer A, Iglesias R, de la Rubia J, Alegre A, Chinea A, Blade J, Lahuerta JJ, San Miguel JF (2013) Phase 2 study of bendamustine, bortezomib (Velcade) and prednisone (BVP) for newly diagnosed multiple myeloma blood (ASH Annual Meeting Abstracts) 122: 2155

  • Morabito F, Bringhen S, Larocca A, Wijermans P, Mateos VM, Gimsing P, Mazzone C, Gottardi D, Omedè P, Zweegman S, Lahuerta J, Zambello R, Musto P, Magarotto V, Schaafsma M, Oriol A, Juliusson G, Cerrato C, Catalano L, Gentile M, Turel IA, Liberati MA, Cavalli M, Rossi D, Passera R, Rosso S, Beksac M, Cavo M, Waage A, San Miguel J, Boccadoro M, Sonneveld P, Palumbo A, Offidani M (2013) Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients: A retrospective case-matched study. Am J Hematol. 2013. doi: 10.1002/ajh.23641

  • Offidani M, Corvatta L, Maracci L, Liberati A.M, Ballanti S, Attolico I, Caraffa P, Alesiani F, Caravita di Toritto T, Gentili S, Tosi P, Brunori M, Derudas D, Ledda A, Gozzetti A, Cellini C, Malerba L, Mele A, Andriani A, Galimberti S, Mondello P, Pulini S, Coppetelli U, Fraticelli P Olivieri A, Leoni P (2013) Efficacy and tolerability of bendamustine bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma: a phase II study, Blood Cancer J Nov 22 (Epub ahead of print)

  • Pönisch W, Mitrou PS, Merkle K-H, Herold M, Assmann M, Wilhelm G, Dachselt K, Richter P, Schirmer V, Schulze A, Subert R, Harksel B, Grobe N, Stelzer E, Schulze M, Bittrich A, Freund M, Pasold R, Friedrich T, Helbig W, Niederwieser D (2006) Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone: a randomized phase III study of the East German study group of haematology and oncology (OSHO). J Cancer Res Clin Oncol 132:205–212

    Article  PubMed  Google Scholar 

  • Pönisch W, Andrea M, Wagner I, Hammerschmidt D, Kreibich U, Schwarzer A, Zehrfeld T, Schwarz M, Winkelmann C, Petros S, Bachmann A, Lindner T, Niederwieser D (2012) Successful treatment of patients with newly diagnosed/untreated multiple myeloma and advanced renal failure using bortezomib in combination with bendamustine and prednisone. J Cancer Res Clin Oncol 138:1405–1412

    Article  PubMed  Google Scholar 

  • Pönisch W, Bourgeois M, Moll B, Heyn S, Jäkel N, Wagner I, Rohrberg R, Hurtz HJ, Schmalfeld M, Aßmann M, Edelmann T, Mohren M, Hoffmann FA, Becker C, Schwarzer A, Schönfelder U, Zehrfeld T, Hensel G, Löschcke K, Krahl R, AL-Ali H, Niederwieser D (2013a) Combined bendamustine, prednisone and bortezomib (BPV) in patients with relapsed or refractory multiple myeloma. J Cancer Res Clin Oncol 139:499–508

    Article  PubMed  Google Scholar 

  • Pönisch W, Moll B, Bourgeois M, Andrea M, Schliwa T, Heyn S, Schmalfeld M, Edelmann T, Becker C, Hoffmann FA, Schwarzer A, Kreibich U, Egert M, Stiegler R, Krahl R, Remane Y, Bachmann A, Lindner T, Weidhase L, Petros S, Fricke S, Vucinic V, Al Ali H, Niederwieser D (2013b) Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment of patients with relapsed or refractory multiple myeloma and light chain-induced renal failure. J Cancer Res Clin Oncol 139:1937–1946

    Article  PubMed  Google Scholar 

  • Preiss R, Teichert J, Pönisch W, Niederwieser D, Matthias M, Merkle KH (2003) Pharmacokinetics and toxicity profile of bendamustine in multiple myeloma patients with end-stage renal disease. Hematolog J 4(Suppl. 1):263

    Google Scholar 

  • Rodon P, Hulin C, Pegourie B, Tiab M, Anglaret B, Benboubker L, Jardel H, Decaux O, Kolb B, Roussel M, Garderet L, Leleu X, Royer B, Banos A, Benramdane R, Cony-Makhoul P, Dib M, Fontan J, Stoppa A, Traullé C, Vilque J, Moreau P, Mathiot C, Avet-Loiseau H (2012) Bendamustine, bortezomib and dexamethasone (BVD) in elderly patients with relapsed/refractory Multiple myeloma: The Intergroupe Francophone du Myelome (IFM) 2009-01 protocol. Haematologica 97: e-Supplement 1, June 14-17, 2012, 400–401

  • Roussou M, Kastritis E, Christoulas D, Migkou M, Gavriatopoulou M, Grapsa I, Psimenou E, Gika D, Terpos E, Dimopoulos MA (2010) Reversibility of renal failure in newly diagnosed patients with multiple myeloma and the role of novel agents. Leuk Res 34:1395–1397

    Article  PubMed  CAS  Google Scholar 

  • Rummel, M.J., Niederle, N., Maschmeyer, G., Banat, G.A., von Grünhagen, U., Losem, C., Kofahl-Krause, D., Heil, G., Welslau, M., Balser, C., Kaiser, U., Weidmann, E., Dürk, H., Ballo, H., Stauch, M., Roller, F., Barth, J., Hoelzer, D., Hinke, A., Brugger, W.; Study group indolent Lymphomas (StiL) (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  Google Scholar 

  • San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H, Richardson PG (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 359:906–917

    Article  PubMed  CAS  Google Scholar 

  • Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM (2012) Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial. J Clin Oncol 30(24):2946–2955

    Article  PubMed  CAS  Google Scholar 

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Conflict of interest

There is no conflict of interest. All authors disclose no financial or personal relationships with other people and Organizations.

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Authors and Affiliations

  1. Department of Hematology, Clinical Oncology and Hemostasiology, University of Leipzig, Leipzig, Germany

    Wolfram Pönisch, Bruno Holzvogt, Madlen Plötze, Marc Andrea, Malvina Bourgeois, Simone Heyn, Rainer Krahl, Yvonne Remane, Evelin Hennig, Thomas Schliwa, Tom Lindner, Thorsten Kaiser, Vladan Vucinic, Gerhard Behre & Dietger Niederwieser

  2. Hospital of Torgau, Torgau, Germany

    Thomas Zehrfeld

  3. Hospital of Plauen, Plauen, Germany

    Doreen Hammerschmidt

  4. Praxis für Hämatologie und Onkologie, Schöneck, Germany

    Maik Schwarz

  5. Medcenter Nordsachsen, Schkeuditz, Germany

    Thomas Edelmann

  6. Praxis für Hämatologie und Onkologie, Rosa-Luxemburg-Str., Leipzig, Germany

    Cornelia Becker

  7. Praxis für Hämatologie, Diakonissenkrankenhaus, Leipzig, Germany

    Franz Albert Hoffmann

  8. Praxis für Hämatologie und Onkologie, Dösen, Germany

    Andreas Schwarzer

  9. Clinical Department III, Heinrich-Braun-Hospital, Zwickau, Germany

    Ute Kreibich

  10. Hospital Görlitz, Görlitz, Germany

    Kerstin Gutsche

  11. Hospital Zittau, Zittau, Germany

    Kolja Reifenrath

  12. Paul-Gerhard-Stift, Wittenberg, Germany

    Cornelia Winkelmann

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  1. Wolfram Pönisch
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  2. Bruno Holzvogt
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  4. Marc Andrea
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Correspondence to Wolfram Pönisch.

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Pönisch, W., Holzvogt, B., Plötze, M. et al. Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment of patients with newly diagnosed/untreated multiple myeloma. J Cancer Res Clin Oncol 140, 1947–1956 (2014). https://doi.org/10.1007/s00432-014-1737-9

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