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Erschienen in: memo - Magazine of European Medical Oncology 1/2015

01.04.2015 | short review

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

verfasst von: Michael Fillitz, Adelheid Seebacher, Michael Panny

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 1/2015

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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.
Literatur
1.
Zurück zum Zitat 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.CrossRefPubMedCentralPubMed 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.CrossRefPubMedCentralPubMed
3.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
4.
Zurück zum Zitat 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.CrossRefPubMedCentralPubMed 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.CrossRefPubMedCentralPubMed
5.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
6.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
7.
Zurück zum Zitat 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. 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.
8.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
9.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
10.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
11.
Zurück zum Zitat 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.CrossRef 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.CrossRef
12.
Zurück zum Zitat Attal M, Harrousseau JL, Leyvraz S, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108:3289–94.CrossRefPubMed Attal M, Harrousseau JL, Leyvraz S, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108:3289–94.CrossRefPubMed
13.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
14.
Zurück zum Zitat 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.CrossRefPubMedCentralPubMed 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.CrossRefPubMedCentralPubMed
15.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
16.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
18.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
19.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
20.
Zurück zum Zitat 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.CrossRefPubMedCentralPubMed 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.CrossRefPubMedCentralPubMed
21.
22.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
23.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
24.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
25.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
26.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
27.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
28.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
29.
Zurück zum Zitat Benboubker L, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10):906–17.CrossRefPubMed Benboubker L, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10):906–17.CrossRefPubMed
30.
Zurück zum Zitat 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.CrossRefPubMedCentralPubMed 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.CrossRefPubMedCentralPubMed
31.
Zurück zum Zitat 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.CrossRef 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.CrossRef
32.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
33.
Zurück zum Zitat 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]. 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.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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. 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.
Metadaten
Titel
Is more better in myeloma? Treatment intensity and outcome in newly diagnosed myeloma patients
verfasst von
Michael Fillitz
Adelheid Seebacher
Michael Panny
Publikationsdatum
01.04.2015
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 1/2015
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-015-0206-8

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