Skip to main content

Advertisement

SpringerLink
Log in

Lenalidomide in combination with bendamustine and prednisolone in relapsed/refractory multiple myeloma: results of a phase 2 clinical trial (OSHO-#077)

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Introduction

While lenalidomide monotherapy is established for relapsed and/or refractory multiple myeloma (MM) treatment, combination therapies including lenalidomide are still under investigation in a number of phase 2/3 studies. In the current study, a treatment regime of lenalidomide (Revlimid®), bendamustine and prednisolone (RBP) was tested in patients with relapsed/refractory MM.

Methods

In the previously completed phase 1 study RBP with a dose of 75 mg/m2 bendamustine days 1–2, prednisolone 100 mg days 1–4 and 25 mg lenalidomide days 1–21 was well tolerated.

Results

Between July 2011 and September 2013, 25 patients were included in this analysis. The median number of previous treatments was 1 (range 1–2). Twenty-two patients (88%) responded after at least two cycles of RBP (one sCR, five nCR, eight VGPR and eight PR). The median time to first haematological response was 28 days, and median time to best response was 56 days. Due to increased haematological toxicity a dose reduction in most patients required in subsequent cycles of therapy. The median progression-free and overall survival was 22 and 38 months, respectively.

Summary

In conclusion RBP is a highly effective therapy for patients with relapsed/refractory MM. In contrast to our phase 1 study, dose reduction was necessary in many patients because of haematological toxicity.

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

  • 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  CAS  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  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Grey-Davies E, Bosworth JL, Boyd KD, Ebdon C, Saso R, Chitnavis D, Mercieca JE, Morgan GJ, Davies FE (2012) Bendamustine, thalidomide and dexamethasone is an effective salvage regimen for advanced stage multiple myeloma. Br J Haematol 156:552–555

    Article  CAS  PubMed  Google Scholar 

  • Kastritis E, Zervas K, Symeonidis A, Terpos E, Anagnostopoulos N, Michali E, Zomas A, Katodritou E, Gika D, Pouli A, Christoulas D, Roussou M, Kartasis Z, Economopoulos T, Dimopoulos MA (2009) Improved survival of patients with multiple myeloma after the introduction of novel agents and the applicability of the international staging system (ISS): an analysis of the Greek Myeloma Study Group (GMSG). Leukemia 23:1152–1157

    Article  CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Knop S, Gerecke C, Liebisch P, Topp MS, Platzbecker U, Sezer O, Vollmuth C, Falk K, Glasmacher A, Maeder U, Einsele H, Bargou RC (2009) Lenalidomide, adriamycin, and dexamethasone (RAD) in patients with relapsed and refractory multiple myeloma: a report from the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myeloma). Blood 113:4137–4143

    Article  CAS  PubMed  Google Scholar 

  • Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell 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  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar SK, Krishnan A, LaPlant B, Laumann K, Roy V, Zimmerman T, Gertz MA, Buadi FK, Stockerl-Goldstein K, Birgin A, Fiala M, Duarte L, Maharaj M, Levy J, Vij R (2015) Bendamustine, lenalidomide, and dexamethasone (BRD) is highly effective with durable responses in relapsed multiple myeloma. Am J Hematol 90:1106–1110

    Article  CAS  PubMed  Google Scholar 

  • Lau I-J, Smith D, Aitchison R, Blesing N, Roberts P, Peniket A, Yong K, Rabin N, Ramasamy K (2015) Bendamustine in combination with thalidomide and dexamethasone is a viable salvage option in myeloma relapsed and/or refractory to bortezomib and lenalidomide. Ann Hematol 94:643–649

    Article  CAS  PubMed  Google Scholar 

  • Lentzsch S, O’Sullivan A, Kennedy RC, Abbas M, Dai L, Pregja SL, Burt S, Boyiadzis M, Roodman GD, Mapara MY, Agha M, Waas J, Shuai Y, Normolle D, Zonder JA (2012) Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase I/II open-label, dose escalation study. Blood 119:4608–4613

    Article  CAS  PubMed  PubMed Central  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  CAS  PubMed  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) ia an active and well tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood 123:985–991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mateos MV, Oriol A, Rosinol L, de Arriba F, Puig N, Martin J, Martinez-Lopez J, Echeveste MA, Sarra J, Ocio EM, Ramirez G, Martinez R, Palomera L, Payer A, Iglesias R, de la Rubia J, Alegre A, Chinea AI, Blade J, Lahuerta JJ, San Miguel JF (2015) Bendamustine, bortezomib and prednisone for the treatment of newly diagnosed multiple myeloma patients: results of a prospective phase 2 Spanish/Pethesma trial. Haematologica 100(8):1096–1102

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mey UJ, Brugger W, Schwarb H, Pederiva S, Schwarzer A, Dechow T, Jehner P, Rauh J, Taverna CJ, Schmid M, Schmidt-Hieber M, Doerfel S, Fischer N, Ruefer A, Ziske C, Knauf W, Cathomas R, von Moos R, Hitz F, Sauter R, Hiendlmeyer E, Cantoni N, Bargetzi M, Driessen C (2017) Bendamustine, lenalidomide and dexamethasone (BRd) has high activity as 2nd—line therapy for relapsed and refractory multiple myeloma—a phase II trial. Br J Haematol 176:770–782

    Article  CAS  PubMed  Google Scholar 

  • Offidani M, Corvatta L, Maracci L, Liberati AM, 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, Oliveri 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 3:e162. doi:10.1038/bcj.2013.58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poenisch W, Plötze M, Holzvogt B, Andrea M, Schliwa T, Zehrfeld T, Hammerschmidt D, Schwarz M, Edelmann T, Becker C, Hoffmann FA, Schwarzer A, Kreibich U, Gutsche K, Reifenrath K, Schwarzbach H, Heyn S, Franke GN, Jentzsch M, Leiblein S, Schwind S, Lange T, Vucinic V, AlAli HK, Niederwieser D (2015) Stem cell mobilization and autologous stem cell transplantation after pretreatment with bendamustine, prednisone and bortezomib (BPV) in newly diagnosed multiple myeloma. J Cancer Res Clin Oncol 141:2013–2022

    Article  CAS  PubMed  Google Scholar 

  • Pönisch W, Mitrou PS, Merkle K, 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, Rozanski M, Goldschmidt H, Hoffmann FA, Boldt T, Schwarzer A, Ritter U, Rohrberg R, Schwalbe E, Uhlig J, Zehrfeld T, Schirmer V, Haas A, Kreibich U, Niederwieser D, East German Study Group of Haematology and Oncology (OSHO) (2008) Combined bendamustine, prednisolone and thalidomide for refractory or relapsed multiple myeloma after autologous stem-cell transplantation or conventional chemo-therapy: results of a Phase I clinical trial. Br J Haematol 143:191–200

    Article  PubMed  Google Scholar 

  • Pönisch W, Heyn S, Beck J, Wagner I, Mohren M, Hoffmann FA, Lange T, Schmalfeld M, Zehrfeld T, Schwarzer A, Winkelmann C, Edelmann T, Röhrborn R, Hebenstreit K, Al-Ali HK, Jäckel N, Niederwieser D (2013a) Lenalidomide, bendamustine and prednisolone exhibits a favourable safety and efficacy profile in relapsed or refractory multiple myeloma: final results of a phase 1 clinical trial OSHO-#077. Br J Haematol 162:202–209

    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, AlAli HK, Niederwieser D (2013b) 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 

  • Pozzi S, Gentile M, Sacchi S, Marcheselli R, Corso A, Cocito F, Musto P, Guarini A, Minoia C, Vincelli I, Ria R, Rivolti E, Mele G, Bari A, Mazzone C, Badiali S, Marcheselli L, Palumbo A, Morabito F (2017) Bendamustine, low-dose dexamethasone, and lenalidomide (BdL) for the treatment of patients with relapsed/refractory multiple myeloma confirms very promising results in a phase I/II study. Leuk Lymphoma 58:552–559

    Article  CAS  PubMed  Google Scholar 

  • Richardson P, Jagannath S, Hussein M, Berenson J, Singhal S, Irwin D, Williams SF, Bensinger W, Badros AZ, Vescio R, Kenvin L, Yu Z, Olesnyckyj M, Zeldis J, Knight R, Anderson KC (2009) Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood 114:772–778

    Article  CAS  PubMed  Google Scholar 

  • Richardson PG, Xie W, Jagannath S, Jakubowiak A, Lonial S, Raje NS, Alsina M, Ghobrial M, Schlossman RL, Munshi NC, Mazumder A, Vesole DH, Kaufman JL, Colson K, McKenney M, Lunde LE, Feather J, Maglio ME, Warren D, Francis D, Hideshima T, Knight R, Esseltine DL, Mitsiades CS, Weller E, Anderson KC (2014) A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood 123:1462–1469

    Google Scholar 

  • Schey SA, Morgan GJ, Ramasamy K, Hazel B, Ladon D, Corderoy S, Jenner M, Phekoo K, Boyd K, Davies FE (2010) The addition of cyclophosphamide to lenalidomide and dexamethasone in multiply relapsed/refractory myeloma patients; a phase I/II study. Br J Haematol 150:326–333

    Article  CAS  PubMed  Google Scholar 

  • Schey S, Brown SR, Tillotson A-L, Williams C, Davies F, Morgan G, Cavenagh J, Cook G, Cook M, Orti G, Morris C, Sherratt D, Flanagan L, Gregory W, Cavet J (2015) Bendamustine, thalidomide and dexamethasone combination therapy for relapsed/refractory myeloma patients: results of the MUKone randomized dose selection trial. Br J Haematol 170:336–348

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology and Oncology, University of Leipzig, Johannisallee 32A, 04103, Leipzig, Germany

    Juliane Beck, Simone Heyn, Thomas Schliwa, Marc Andrea, Marius Bill, Madlen Jentzsch, Sebastian Schwind, Dietger Niederwieser & Wolfram Pönisch

  2. Haematology Practice, Strümpelstrasse 41, Leipzig, Germany

    Andreas Schwarzer

  3. Department of Haematology and Oncology, Klinikum Südstadt Rostock, Rostock, Germany

    Dietrich Gläser

  4. Department of Haematology and Oncology, University of Jena, Jena, Germany

    Lars-Olof Mügge

  5. Haematology Practice, Schulstrasse 1, Naunhof, Germany

    Jens Uhlig

  6. Department of Haematology and Oncology, University of Rostock, Rostock, Germany

    Brigitte Kragl

  7. Department of Haematology and Oncology, Johanniter Krankenhaus, Stendal, Germany

    Martin Mohren

  8. Haematology Practice, Biedermannstrasse 84, Leipzig, Germany

    Franz Albert Hoffmann & Cornelia Becker

  9. Department of Haematology and Oncology, Asklepios Hospital, Weissenfels, Germany

    Thoralf Lange

  10. Department of Haematology and Oncology, Hospital Johann Kentmann, Torgau, Germany

    Thomas Zehrfeld

  11. Department of Haematology and Oncology, Heinrich-Braun-Hospital, Zwickau, Germany

    Ute Kreibich

  12. Department of Haematology and Oncology, Paul Gerhardt Stift, Wittenberg, Germany

    Cornelia Winkelmann

  13. Haematology Practice, Theodor-Heuss-Str. 2, Schkeuditz, Germany

    Thomas Edelmann

Authors
  1. Juliane Beck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andreas Schwarzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dietrich Gläser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lars-Olof Mügge
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jens Uhlig
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Simone Heyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Brigitte Kragl
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Martin Mohren
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Franz Albert Hoffmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Thoralf Lange
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Thomas Schliwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Thomas Zehrfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Cornelia Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ute Kreibich
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Cornelia Winkelmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Thomas Edelmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Marc Andrea
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Marius Bill
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Madlen Jentzsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Sebastian Schwind
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Dietger Niederwieser
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Wolfram Pönisch
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

WP and SH designed the study. JB, WP, TS and SH collected the data, analysed and interpreted the data, performed statistical analysis and wrote the manuscript. MM, FAH and TL were members of independent data-monitoring committee. JB, AS, DG, LOM, JU, SH, BK, TZ, CB, UK, CW, TE, MA, MB, MJ, SS, DN and WP enrolled patients and collected the data. All authors reviewed and revised the manuscript.

Corresponding author

Correspondence to Wolfram Pönisch.

Ethics declarations

Conflict of interest

This study was supported in part by research funding from Celgene, Mundipharma and Amgen. We want to thank our contract research organisation ClinAssess for performing data management and site management for all study centres. No authors declare competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Beck, J., Schwarzer, A., Gläser, D. et al. Lenalidomide in combination with bendamustine and prednisolone in relapsed/refractory multiple myeloma: results of a phase 2 clinical trial (OSHO-#077). J Cancer Res Clin Oncol 143, 2545–2553 (2017). https://doi.org/10.1007/s00432-017-2504-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-017-2504-5

Keywords

Search

Navigation