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Myeloma

Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients

Leukemia volume 28, pages 690–693 (2014)Cite this article

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Abstract

Prior studies have shown that myeloma patients exhibiting either genetically defined high-risk disease or plasma cell leukemia have a poor outcome with a median overall survival (OS) of ⩽3 years. Results of IFM 2005-01 and 02 suggest that relatively limited bortezomib-containing induction regimens did not produce a major survival benefit among these patients. However, results of recent studies suggest that combination therapy may benefit these patients when given early and again later in the treatment. We evaluated a combination maintenance/consolidation regimen (RVD) following autologous stem cell transplant (ASCT) for high-risk patients to evaluate the impact of this approach on outcome. Following initiation of RVD maintenance, 51% of patients achieved stringent complete response (sCR), with 96% achieving at least VGPR as best response. Median progression free survival (PFS) for all patients is 32 months with a 3-year OS of 93%. The regimen was well tolerated with no grade 3/4 neuropathy. Early ASCT followed by RVD maintenance is a promising strategy for high-risk myeloma patients and delivered excellent response rates, and promising PFS and OS.

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References

  1. Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood 2007; 109: 3489–3495.

    Article  CAS  Google Scholar 

  2. Barlogie B, Anaissie E, Van Rhee F, Haessler J, Hollmig K, Pineda-Roman M et al. Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. Br J Haematol 2007; 138: 176–185.

    Article  CAS  Google Scholar 

  3. Avet-Loiseau H, Leleu X, Roussel M, Moreau P, Guerin-Charbonnel C, Caillot D et al. Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol 2010; 28: 4630–4634.

    Article  CAS  Google Scholar 

  4. Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D et al. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood 2012; 120: 9–19.

    Article  CAS  Google Scholar 

  5. Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B et al. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood 2012; 119: 940–948.

    Article  CAS  Google Scholar 

  6. Mahindra A, Kalaycio ME, Vela-Ojeda J, Vesole DH, Zhang MJ, Li P et al. Hematopoietic cell transplantation for primary plasma cell leukemia: results from the Center for International Blood and Marrow Transplant Research. Leukemia 2012; 26: 1091–1097.

    Article  CAS  Google Scholar 

  7. Chaoui D, Leleu X, Roussel M, Royer B, Rubio M-t, Ducastelle S et al. Has the Prognostic of Primary Plasma Cell Leukemia Improved with New drugs? ASH Annual Meeting Abstracts 2009; 114: 3869.

    Google Scholar 

  8. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002; 99: 4525–4530.

    Article  CAS  Google Scholar 

  9. Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010; 116: 679–686.

    Article  CAS  Google Scholar 

  10. Richardson PG, Jagannath S, Jakubowiak AJ, Lonial S, Raje N, Alsina M et al. Phase II Trial of Lenalidomide, Bortezomib, and Dexamethasone In Patients (pts) with Relapsed and Relapsed/Refractory Multiple Myeloma (MM): Updated Efficacy and Safety Data After >2 Years of Follow-up. ASH Annual Meeting Abstracts 2010; 116: 3049.

    Google Scholar 

  11. Richardson PG, Weller E, Jagannath S, Avigan DE, Alsina M, Schlossman RL et al. Multicenter, phase i, dose-escalation trial of lenalidomide plus bortezomib for relapsed and relapsed/refractory multiple myeloma. J Clin Oncol 2009; 27: 5713–5719.

    Article  CAS  Google Scholar 

  12. Anderson KC, Jagannath S, Jakubowiak A, Lonial S, Raje N, Alsina M et al. Lenalidomide, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma (MM): Encouraging outcomes and tolerability in a phase II study. ASCO Meeting Abstracts 2009; 27: 8536.

    Google Scholar 

  13. Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood 2012; 119: 4375–4382.

    Article  CAS  Google Scholar 

  14. Durie BGM, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–1473.

    Article  CAS  Google Scholar 

  15. Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J et al. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood 2012; 120: 1589–1596.

    Article  Google Scholar 

  16. Kuehl WM, Bergsagel PL . Molecular pathogenesis of multiple myeloma and its premalignant precursor. J Clin Invest 2012; 122: 3456–3463.

    Article  CAS  Google Scholar 

  17. Harousseau J-L, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol 2010; 28: 4621–4629.

    Article  CAS  Google Scholar 

  18. Sonneveld P, Schmidt-Wolf IGH, van der Holt B, el Jarari L, Bertsch U, Salwender H et al. 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 2012; 30: 2946–2955.

    Article  CAS  Google Scholar 

  19. Mateos M-V, Oriol A, Martínez-López J, Gutiérrez N, Teruel A-I, López de la Guía A et al. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood 2012; 120: 2581–2588.

    Article  CAS  Google Scholar 

  20. Nair B, van Rhee F, Shaughnessy JD, Anaissie E, Szymonifka J, Hoering A et al. Superior results of Total Therapy 3 (2003-33) in gene expression profiling–defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenance. Blood 2010; 115: 4168–4173.

    Article  CAS  Google Scholar 

  21. D'Arena G, Valentini CG, Pietrantuono G, Guariglia R, Martorelli MC, Mansueto G et al. Frontline chemotherapy with bortezomib-containing combinations improves response rate and survival in primary plasma cell leukemia: a retrospective study from GIMEMA Multiple Myeloma Working Party. Ann Oncol 2012; 23: 1499–1502.

    Article  CAS  Google Scholar 

  22. Richardson PGG, Berdeja JG, Niesvizky R, Lonial S, Roy V, Hari P et al. Oral weekly MLN9708, an investigational proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients (pts) with previously untreated multiple myeloma (MM): A phase I/II study. ASCO Meeting Abstracts 2012; 30 (15 suppl): 8033.

    Google Scholar 

  23. Vij R, Wang M, Kaufman JL, Lonial S, Jakubowiak AJ, Stewart AK et al. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood 2012; 119: 5661–5670.

    Article  Google Scholar 

  24. Lacy MQ, Hayman SR, Gertz MA, Dispenzieri A, Buadi F, Kumar S et al. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol 2009; 27: 5008–5014.

    Article  CAS  Google Scholar 

  25. Lonial S, Vij R, Harousseau J-L, Facon T, Moreau P, Mazumder A et al. Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol 2012; 30: 1953–1959.

    Article  CAS  Google Scholar 

  26. Lokhorst HM, Plesner T, Gimsing P, Nahi H, Minnema M, Lassen UN et al. Phase I/II dose-escalation study of daratumumab in patients with relapsed or refractory multiple myeloma. ASCO Meeting Abstracts 2013; 31 (15 suppl): 8512.

    Google Scholar 

  27. Kaufman JL, Fabre C, Lonial S, Richardson PG . Histone deacetylase inhibitors in multiple myeloma: rationale and evidence for their use in combination therapy. Clin Lymphoma Myeloma Leuk 2013; 13: 370–376.

    Article  CAS  Google Scholar 

  28. Richardson PG, Chanan-Khan AA, Lonial S, Krishnan AY, Carroll MP, Alsina M et al. Tanespimycin and bortezomib combination treatment in patients with relapsed or relapsed and refractory multiple myeloma: results of a phase 1/2 study. Br J Haematol 2011; 153: 729–740.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology and Medical Oncology Winship Cancer Center, Emory University, Atlanta, GA, USA

    A K Nooka, J L Kaufman, S Muppidi, A Langston, L T Heffner, C Gleason, D Casbourne, L H Boise & S Lonial

  2. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA

    D Saxe

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  1. A K Nooka
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  2. J L Kaufman
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  3. S Muppidi
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  4. A Langston
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  7. D Casbourne
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Correspondence to S Lonial.

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Competing interests

Jonathan Kaufman has received research support from Celgene, Novartis and Merck and served as a consultant for Celgene, Millennium, Janssen, Novartis and Onyx. Sagar Lonial has served as a consultant for Celgene, BMS, Novartis, Onyx, Sanofi and Millennium. Lawrence Boise served as a consultant for Onyx. Charise Gleason served as a consultant for Millennium. Leonard Heffner has received honoraria from Amgen, Spectrum and Pharmacyclics. The other authors declare no conflict of interest.

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AKN, JLK and SL designed the study; AKN, CG and DC analyzed the results and made the tables and figures; AKN, JLK, SL, AL, LHB, SM, LTH and DS prepared, reviewed and edited the final manuscript. All authors were fully responsible for the content.

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Nooka, A., Kaufman, J., Muppidi, S. et al. Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients. Leukemia 28, 690–693 (2014). https://doi.org/10.1038/leu.2013.335

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