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Is more better in myeloma? Treatment intensity and outcome in newly diagnosed myeloma patients

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Abstract

During the course of disease multiple myeloma subclones acquire more and more additional genetic changes causing an aggressive proliferative growth with less responsiveness to therapeutic agents. On the other hand new therapeutic options are getting available, leading to the question, if a more intensive treatment in newly diagnosed myeloma patients may result in a better outcome concerning progression-free survival, quality of life and overall survival. In newly diagnosed myeloma patients, physicians have to distinguish between patients eligible for autologous stem cell transplantion (ASCT) and patients ineligible for ASCT. Transplant eligibility is mainly based on biological age, performance status and co-morbidities. New data suggest that prolonged treatment—synonymously called maintenance therapy—may lead to additional survival benefit even in the elderly/frail patient group. Yet there is no clear data on overall survival for prolonged treatment. At time the first-line armoury in myeloma consists of chemotherapy, steroids, proteasome inhibitors and immunmodulatory/antiangiogenetic drugs. The role of new antibodies in myeloma treatment is evolving but there is only limited (but promising) data available yet. New agents might reduce the therapeutic side-effects of an intensive treatment despite increasing efficacy as shown, e.g., for the new proteasome inhibitor carfilzomib. In the first-line setting, other new oral proteasome inhibitors with low dose-limiting neurotoxicity rates will be available shortly. In this short review, therapeutic strategies will be discussed focusing on treatment intensity.

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References

  1. Rajkumar SV, Gupta V, Fonesca R, et al. Impact of primary molecular cytogenetic abnormities and risk of progression in smoldering multiple. Leukemia. 2013;27:1738–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Keats JJ, Chesi M, Egan JB, et al. Clonal competition with alternating dominance in multiple myeloma. Blood. 2012;120(5):1067–76.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Mateos MV, Hernández MT, Giraldo P, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013;369(5):438–47.

    Article  CAS  PubMed  Google Scholar 

  4. Palumbo A, Waage A, Hulin C, et al. Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials. Haematologica. 2013;98(1):87–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Kumar S, Flinn I, Richardson PG, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012;119(19):4375–82.

    Article  CAS  PubMed  Google Scholar 

  6. Garderet L, Iacobelli S, Moreau P, et al. Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2012;30(20):2475–82.

    Article  CAS  PubMed  Google Scholar 

  7. Francesca Gay F, Larocca A, Wijermans P, et al. Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood. 2001;117:3025–31.

    Google Scholar 

  8. Sonneveld P, Schmidt-Wolf IG, van der Holt B, 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(24):2946–55.

    Article  CAS  PubMed  Google Scholar 

  9. Cavo M, Pantani L, Petrucci MT, 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(1):9–19.

    Article  CAS  PubMed  Google Scholar 

  10. Cavo M, Tacchetti P, Patriarca F, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010;376:2075–85.

    Article  CAS  PubMed  Google Scholar 

  11. Spencer A, Prince HM, Roberts AW, et al. Consolidation therapy with low dose thalidomide and prednisone prolongs the survival of multiple myeloma patients undergoing a single autologous stem cell transplantation procedure. Clin Oncol. 2009;27:1788–93.

    Article  CAS  Google Scholar 

  12. Attal M, Harrousseau JL, Leyvraz S, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108:3289–94.

    Article  CAS  PubMed  Google Scholar 

  13. Attal M, Lauwers-Cances V, Marit G, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366(19):1782–91.

    Article  CAS  PubMed  Google Scholar 

  14. McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366(19):1770–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Palumbo A, Cavallo F, Gay F, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895–905.

    Article  PubMed  Google Scholar 

  16. Cavo M, Salwender H, Rosiñol L, et al. Clinical allogeneic and autologous transplantation—results: evidence-based decision making II—transplantation for lymphoma and plasma cell disorders. ASH 2013. Abstract 767.

  17. Leleu X, Fouquet G, Hebraud B, et al. Consolidation with VTd significantly improves the complete remission rate and time to progression following VTd induction and single autologous stem cell transplantation in multiple myeloma. Leukemia. 2013;27(11):2242–4.

    Article  CAS  PubMed  Google Scholar 

  18. Neben K, Lokhorst HM, Jauch A, et al. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012;119:940–8.

    Article  CAS  PubMed  Google Scholar 

  19. Donato M, Siegel DS, Vesole DH, et al. The graft-versus-myeloma effect: chronic graft-versus-host disease but not acute graft-versus-host disease prolongs survival in patients with multiple myeloma receiving allogeneic transplantation. Biol Blood Marrow Transplant. 2014;20(8):1211–6.

    Article  CAS  PubMed  Google Scholar 

  20. Freytes CO, Vesole DH, LeRademacher J, et al. Second transplants for multiple myeloma relapsing after a previous autotransplant-reduced-intensity allogeneic vs autologous transplantation. Bone Marrow Transplant. 2014;49(3):416–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Barlogie B, Mitchell A, van Rhee F, et al. Curing myeloma at last: defining criteria and providing the evidence. Blood. 2014;124(20):3043–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Facon T, Mary JY, Hulin C, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet. 2007;370:1209–18.

    Article  CAS  PubMed  Google Scholar 

  23. Hulin C, Facon T, Rodon P, et al. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol. 2009;27:3664–70.

    Article  CAS  PubMed  Google Scholar 

  24. Palumbo A, Bringhen S, Caravita T, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006;367:825–31.

    Article  CAS  PubMed  Google Scholar 

  25. Waage A, Gimsing P, Fayers P, et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood. 2010;116:1405–12.

    Article  CAS  PubMed  Google Scholar 

  26. Wijermans P, Schaafsma M, Termorshuizen F, et al. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol. 2010;28:3160–6.

    Article  CAS  PubMed  Google Scholar 

  27. San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359:906–17.

    Article  CAS  PubMed  Google Scholar 

  28. Mateos M-V, Richardson PG, Schlag R, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol. 2010;28:2259–66.

    Article  CAS  PubMed  Google Scholar 

  29. Benboubker L, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10):906–17.

    Article  CAS  PubMed  Google Scholar 

  30. Ludwig H, Adam Z, Tóthová E, et al. Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma. Haematologica. 2010;95(9):1548–54.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Mateos MV, Oriol A, Martínez-López J, Teruel AI, et al. Update of the GEM2005 trial comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators? Blood. 2014;127(12):1887–93.

    Article  Google Scholar 

  32. Palumbo A, Bringhen S, Larocca A, et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. J Clin Oncol. 2014;32(7):634–40.

    Article  CAS  PubMed  Google Scholar 

  33. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2014 [Epub ahead of print].

  34. Richardson P, Jagannath S, Moreau S, et al. Final results for the 1703 phase 1b/2 study of elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma. ASH 2014. Abstract 302.

  35. Martin TG, III, Baz R, Benson DM, Jr., et al. A phase Ib dose escalation trial of SAR650984 (Anti-CD-38 mAb) in combination with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma. ASH 2014. Abstract 83.

  36. Plesner T, Arkenau H-T, Lokhorst HM, et al. Safety and efficacy of daratumumab with lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma. ASH 2014. Abstract 84.

  37. Moreau P, Mateos M-V, Bladé J, et al. An open-label, multicenter, phase 1b study of daratumumab in combination with backbone regimens in patients with multiple myeloma. 2014 ASH 2014. Abstract 176.

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Fillitz, M., Seebacher, A. & Panny, M. Is more better in myeloma? Treatment intensity and outcome in newly diagnosed myeloma patients. memo 8, 22–25 (2015). https://doi.org/10.1007/s12254-015-0206-8

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  • DOI: https://doi.org/10.1007/s12254-015-0206-8

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