Skip to main content
Top
Published in: International Journal of Clinical Oncology 3/2015

01-06-2015 | Review Article

Current therapeutic strategies for multiple myeloma

Authors: Yoshihiro Torimoto, Motohiro Shindo, Katsuya Ikuta, Yutaka Kohgo

Published in: International Journal of Clinical Oncology | Issue 3/2015

Login to get access

Abstract

The introduction of novel molecular targeting agents against multiple myeloma has dramatically and rapidly changed the therapeutic strategies for this incurable hematologic disease. Novel agents such as thalidomide, bortezomib and lenalidomide have significantly improved the response rate, progression-free survival, and overall survival compared with conventional chemotherapies, and made it easy to control the disease for longer periods of time. Initial therapies for newly diagnosed myeloma patients depend on the individual’s clinical condition. Induction therapy with novel agents and high-dose chemotherapy followed by autologous stem cell transplantation is a standard therapy for newly diagnosed younger myeloma patients. On the other hand, several combinations of novel agents and other drugs (melphalan, prednisone, dexamethasone, etc.) are widely used as initial therapy for transplantation-ineligible myeloma patients. Although the clinical advantage of maintenance therapy after induction therapy has been reported, it is not recommend in routine practice. Maintenance therapy would be an option for some patients. Despite the significant improvements with the use of novel agents, the majority of patients eventually relapse. A number of treatment options including novel agents, which demonstrated marked clinical effects, are reported in the setting of salvage therapy. The choice of appropriate therapy for relapsed or refractory patients must take the disease status or patient status in consideration. Furthermore, a new generation of novel agents such as pomalidomide, carfilzomib or panobinostat has recently become available for relapsed or refractory myeloma. It is necessary to determine the optimal combination of drugs, administration timing and patients to be treated in future clinical trials.
Literature
1.
go back to reference International Myeloma Working Group (2003) Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 121:749–757CrossRef International Myeloma Working Group (2003) Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 121:749–757CrossRef
2.
go back to reference Alexanian R, Bergsagel DE, Migliore PJ et al (1968) Melphalan therapy for plasma cell myeloma. Blood 31:1–10PubMed Alexanian R, Bergsagel DE, Migliore PJ et al (1968) Melphalan therapy for plasma cell myeloma. Blood 31:1–10PubMed
3.
go back to reference Myeloma Trialists’ Collaborative Group (1998) Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6633 patients from 27 randomized trials. J Clin Oncol 16:3832–3842 Myeloma Trialists’ Collaborative Group (1998) Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6633 patients from 27 randomized trials. J Clin Oncol 16:3832–3842
4.
go back to reference Koreth J, Cutler CS, Djulbegovic B et al (2007) High-dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: a systematic review and meta-analysis of randomized controlled trials. Biol Blood Marrow Transplant 13:183–196PubMedCrossRef Koreth J, Cutler CS, Djulbegovic B et al (2007) High-dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: a systematic review and meta-analysis of randomized controlled trials. Biol Blood Marrow Transplant 13:183–196PubMedCrossRef
5.
go back to reference Attal M, Harousseau JL, Stoppa AM et al (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med 335:91–97PubMedCrossRef Attal M, Harousseau JL, Stoppa AM et al (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med 335:91–97PubMedCrossRef
6.
go back to reference Dimopoulos M, Spencer A, Attal M et al (2007) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357:2123–2132PubMedCrossRef Dimopoulos M, Spencer A, Attal M et al (2007) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357:2123–2132PubMedCrossRef
7.
go back to reference Richardson PG, Sonneveld P, Schuster MW et al (2005) Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352:2487–2498PubMedCrossRef Richardson PG, Sonneveld P, Schuster MW et al (2005) Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352:2487–2498PubMedCrossRef
8.
10.
go back to reference Ludwig H, Sonneveld P, Davies F et al (2014) European perspective on multiple myeloma treatment strategies in 2014. Oncologist 19:829–844PubMedCrossRef Ludwig H, Sonneveld P, Davies F et al (2014) European perspective on multiple myeloma treatment strategies in 2014. Oncologist 19:829–844PubMedCrossRef
11.
go back to reference Palumbo A, Rajkumar SV, San Miguel JF et al (2014) International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol 32:587–600PubMedCentralPubMedCrossRef Palumbo A, Rajkumar SV, San Miguel JF et al (2014) International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol 32:587–600PubMedCentralPubMedCrossRef
12.
go back to reference Kumar SK, Dispenzieri A, Lacy MQ et al (2014) Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia 28:1122–1128PubMedCentralPubMedCrossRef Kumar SK, Dispenzieri A, Lacy MQ et al (2014) Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia 28:1122–1128PubMedCentralPubMedCrossRef
13.
go back to reference Rajkumar SV, Rosiñol L, Hussein M et al (2008) Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol 26:2171–2177PubMedCentralPubMedCrossRef Rajkumar SV, Rosiñol L, Hussein M et al (2008) Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol 26:2171–2177PubMedCentralPubMedCrossRef
14.
go back to reference Rajkumar SV, Jacobus S, Callander NS et al (2010) Eastern Cooperative Oncology Group. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 11:29–37PubMedCentralPubMedCrossRef Rajkumar SV, Jacobus S, Callander NS et al (2010) Eastern Cooperative Oncology Group. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 11:29–37PubMedCentralPubMedCrossRef
15.
go back to reference Cavo M, Zamagni E, Tosi P et al (2005) Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood 106:35–39PubMedCrossRef Cavo M, Zamagni E, Tosi P et al (2005) Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood 106:35–39PubMedCrossRef
16.
go back to reference Morgan GJ, Davies FE, Gregory WM et al (2012) Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica 97:442–450PubMedCentralPubMedCrossRef Morgan GJ, Davies FE, Gregory WM et al (2012) Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica 97:442–450PubMedCentralPubMedCrossRef
17.
go back to reference Zonder JA, Crowley J, Hussein MA et al (2010) Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood 116:5838–5841PubMedCentralPubMedCrossRef Zonder JA, Crowley J, Hussein MA et al (2010) Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood 116:5838–5841PubMedCentralPubMedCrossRef
18.
go back to reference Sonneveld P, Goldschmidt H, Rosiñol L et al (2013) Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials. J Clin Oncol 31:3279–3287PubMedCrossRef Sonneveld P, Goldschmidt H, Rosiñol L et al (2013) Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials. J Clin Oncol 31:3279–3287PubMedCrossRef
19.
go back to reference Harousseau JL, Attal M, Avet-Loiseau H et al (2010) 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 28:4621–4629PubMedCrossRef Harousseau JL, Attal M, Avet-Loiseau H et al (2010) 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 28:4621–4629PubMedCrossRef
20.
go back to reference Nooka AK, Kaufman JL, Behera M et al (2013) Bortezomib-containing induction regimens in transplant-eligible myeloma patients: a meta-analysis of phase 3 randomized clinical trials. Cancer 119:4119–4128PubMedCrossRef Nooka AK, Kaufman JL, Behera M et al (2013) Bortezomib-containing induction regimens in transplant-eligible myeloma patients: a meta-analysis of phase 3 randomized clinical trials. Cancer 119:4119–4128PubMedCrossRef
21.
go back to reference Sonneveld P, Schmidt-Wolf IG, van der Holt B et al (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 30:2946–2955PubMedCrossRef Sonneveld P, Schmidt-Wolf IG, van der Holt B et al (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 30:2946–2955PubMedCrossRef
22.
go back to reference Cavo M, Tacchetti P, Patriarca F et al (2010) 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 376:2075–2085PubMedCrossRef Cavo M, Tacchetti P, Patriarca F et al (2010) 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 376:2075–2085PubMedCrossRef
23.
go back to reference Kumar S, Flinn I, Richardson PG et al (2012) Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood 119:4375–4382PubMedCrossRef Kumar S, Flinn I, Richardson PG et al (2012) Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood 119:4375–4382PubMedCrossRef
24.
go back to reference Richardson PG, Weller E, Lonial S et al (2010) Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 116:679–686PubMedCentralPubMedCrossRef Richardson PG, Weller E, Lonial S et al (2010) Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 116:679–686PubMedCentralPubMedCrossRef
25.
go back to reference Rosiñol L, Oriol A, Teruel AI et al (2012) Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood 120:1589–1596PubMedCrossRef Rosiñol L, Oriol A, Teruel AI et al (2012) Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood 120:1589–1596PubMedCrossRef
26.
go back to reference Moreau P, Facon T, Attal M et al (2002) Comparison of 200 mg/m2 melphalan and 8 Gy total body irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood 99:731–735PubMedCrossRef Moreau P, Facon T, Attal M et al (2002) Comparison of 200 mg/m2 melphalan and 8 Gy total body irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood 99:731–735PubMedCrossRef
27.
go back to reference Roussel M, Moreau P, Huynh A et al (2010) Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood 115:32–37PubMedCrossRef Roussel M, Moreau P, Huynh A et al (2010) Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood 115:32–37PubMedCrossRef
28.
go back to reference Blanes M, Lahuerta JJ, González JD et al (2013) Intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: a matched comparison to a melphalan-only approach. Biol Blood Marrow Transplant 19:69–74PubMedCrossRef Blanes M, Lahuerta JJ, González JD et al (2013) Intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: a matched comparison to a melphalan-only approach. Biol Blood Marrow Transplant 19:69–74PubMedCrossRef
29.
go back to reference Mark TM, Reid W, Niesvizky R (2013) A phase 1 study of bendamustine and melphalan conditioning for autologous stem cell transplantation in multiple myeloma. Biol Blood Marrow Transplant 19:831–837PubMedCentralPubMedCrossRef Mark TM, Reid W, Niesvizky R (2013) A phase 1 study of bendamustine and melphalan conditioning for autologous stem cell transplantation in multiple myeloma. Biol Blood Marrow Transplant 19:831–837PubMedCentralPubMedCrossRef
30.
go back to reference Sonneveld P, van der Holt B, Segeren CM et al (2007) Intermediate-dose melphalan compared with myeloablative treatment in multiple myeloma: long-term follow-up of the Dutch Cooperative Group HOVON 24 trial. Haematologica 92:928–935PubMedCrossRef Sonneveld P, van der Holt B, Segeren CM et al (2007) Intermediate-dose melphalan compared with myeloablative treatment in multiple myeloma: long-term follow-up of the Dutch Cooperative Group HOVON 24 trial. Haematologica 92:928–935PubMedCrossRef
31.
go back to reference Cavo M, Tosi P, Zamagni E (2007) Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol 25:2434–2441PubMedCrossRef Cavo M, Tosi P, Zamagni E (2007) Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol 25:2434–2441PubMedCrossRef
32.
go back to reference Attal M, Harousseau JL, Facon T et al (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495–2502PubMedCrossRef Attal M, Harousseau JL, Facon T et al (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495–2502PubMedCrossRef
33.
go back to reference Cavo M, Pantani L, Petrucci MT et al (2012) 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 120:9–19PubMedCrossRef Cavo M, Pantani L, Petrucci MT et al (2012) 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 120:9–19PubMedCrossRef
34.
go back to reference Ladetto M, Pagliano G, Ferrero S et al (2010) Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol 28:2077–2084PubMedCrossRef Ladetto M, Pagliano G, Ferrero S et al (2010) Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol 28:2077–2084PubMedCrossRef
35.
go back to reference Mellqvist UH, Gimsing P, Hjertner O et al (2013) Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood 121:4647–4654PubMedCentralPubMedCrossRef Mellqvist UH, Gimsing P, Hjertner O et al (2013) Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood 121:4647–4654PubMedCentralPubMedCrossRef
36.
go back to reference Attal M, Harousseau JL, Leyvraz S et al (2006) Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 108:3289–3294PubMedCrossRef Attal M, Harousseau JL, Leyvraz S et al (2006) Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 108:3289–3294PubMedCrossRef
37.
go back to reference Morgan GJ, Davies FE, Gregory WM et al (2013) Long-term follow-up of MRC Myeloma IX trial: survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res 19:6030–6038PubMedCrossRef Morgan GJ, Davies FE, Gregory WM et al (2013) Long-term follow-up of MRC Myeloma IX trial: survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res 19:6030–6038PubMedCrossRef
38.
go back to reference Spencer A, Prince HM, Roberts AW et al (2009) Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol 27:1788–1793PubMedCrossRef Spencer A, Prince HM, Roberts AW et al (2009) Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol 27:1788–1793PubMedCrossRef
39.
go back to reference Attal M, Lauwers-Cances V, Marit G et al (2012) Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 366:1782–1791PubMedCrossRef Attal M, Lauwers-Cances V, Marit G et al (2012) Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 366:1782–1791PubMedCrossRef
40.
41.
go back to reference Palumbo A, Bringhen S, Kumar SK et al (2014) Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data. Lancet Oncol 15:333–342PubMedCrossRef Palumbo A, Bringhen S, Kumar SK et al (2014) Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data. Lancet Oncol 15:333–342PubMedCrossRef
42.
go back to reference Palumbo A, Cavallo F, Gay F et al (2014) Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med 371:895–905PubMedCrossRef Palumbo A, Cavallo F, Gay F et al (2014) Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med 371:895–905PubMedCrossRef
44.
go back to reference Palumbo A, Bringhen S, Liberati AM et al (2008) Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood 112:3107–3114PubMedCrossRef Palumbo A, Bringhen S, Liberati AM et al (2008) Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood 112:3107–3114PubMedCrossRef
45.
go back to reference Wijermans P, Schaafsma M, Termorshuizen F et al (2010) 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 28:3160–3166PubMedCrossRef Wijermans P, Schaafsma M, Termorshuizen F et al (2010) 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 28:3160–3166PubMedCrossRef
46.
go back to reference Facon T, Mary JY, Hulin C et al (2007) 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 370:1209–1218PubMedCrossRef Facon T, Mary JY, Hulin C et al (2007) 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 370:1209–1218PubMedCrossRef
47.
go back to reference Hulin C, Facon T, Rodon P et al (2009) 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 27:3664–3670PubMedCrossRef Hulin C, Facon T, Rodon P et al (2009) 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 27:3664–3670PubMedCrossRef
48.
go back to reference Waage A, Gimsing P, Fayers P et al (2010) Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood 116:1405–1412PubMedCrossRef Waage A, Gimsing P, Fayers P et al (2010) Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood 116:1405–1412PubMedCrossRef
49.
go back to reference Beksac M, Haznedar R, Firatli-Tuglular T et al (2011) Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group. Eur J Haematol 86:16–22PubMedCrossRef Beksac M, Haznedar R, Firatli-Tuglular T et al (2011) Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group. Eur J Haematol 86:16–22PubMedCrossRef
50.
go back to reference Fayers PM, Palumbo A, Hulin C et al (2011) Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood 118:1239–1247PubMedCrossRef Fayers PM, Palumbo A, Hulin C et al (2011) Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood 118:1239–1247PubMedCrossRef
51.
go back to reference Palumbo A, Falco P, Corradini P et al (2007) Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA–Italian Multiple Myeloma Network. J Clin Oncol 25:4459–4465PubMedCrossRef Palumbo A, Falco P, Corradini P et al (2007) Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA–Italian Multiple Myeloma Network. J Clin Oncol 25:4459–4465PubMedCrossRef
52.
go back to reference Palumbo A, Hajek R, Delforge M et al (2012) Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 366:1759–1769PubMedCrossRef Palumbo A, Hajek R, Delforge M et al (2012) Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 366:1759–1769PubMedCrossRef
53.
go back to reference Benboubker L, Dimopoulos MA, Dispenzieri A et al (2014) Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med 371:906–917PubMedCrossRef Benboubker L, Dimopoulos MA, Dispenzieri A et al (2014) Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med 371:906–917PubMedCrossRef
54.
go back to reference San Miguel JF, Schlag R, Khuageva NK et al (2013) Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol 31:448–455PubMedCrossRef San Miguel JF, Schlag R, Khuageva NK et al (2013) Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol 31:448–455PubMedCrossRef
55.
go back to reference Mateos MV, Richardson PG, Schlag R et al (2010) 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 28:2259–2266PubMedCrossRef Mateos MV, Richardson PG, Schlag R et al (2010) 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 28:2259–2266PubMedCrossRef
56.
go back to reference Bringhen S, Larocca A, Rossi D et al (2010) Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood 116:4745–4753PubMedCrossRef Bringhen S, Larocca A, Rossi D et al (2010) Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood 116:4745–4753PubMedCrossRef
57.
go back to reference Mateos MV, Oriol A, Martínez-López J et al (2010) Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 11:934–941PubMedCrossRef Mateos MV, Oriol A, Martínez-López J et al (2010) Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 11:934–941PubMedCrossRef
58.
go back to reference Moreau P, Pylypenko H, Grosicki S et al (2011) Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol 12:431–440PubMedCrossRef Moreau P, Pylypenko H, Grosicki S et al (2011) Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol 12:431–440PubMedCrossRef
59.
go back to reference Palumbo A, Bringhen S, Caravita T et al (2006) Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 367:825–831PubMedCrossRef Palumbo A, Bringhen S, Caravita T et al (2006) Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 367:825–831PubMedCrossRef
60.
go back to reference Morgan GJ, Gregory WM, Davies FE et al (2012) The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood 119:7–15PubMedCrossRef Morgan GJ, Gregory WM, Davies FE et al (2012) The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood 119:7–15PubMedCrossRef
61.
go back to reference Palumbo A, Bringhen S, Rossi D et al (2010) Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol 28:5101–5109PubMedCrossRef Palumbo A, Bringhen S, Rossi D et al (2010) Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol 28:5101–5109PubMedCrossRef
62.
go back to reference Palumbo A, Bringhen S, Larocca A et al (2014) 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 32:634–6340PubMedCrossRef Palumbo A, Bringhen S, Larocca A et al (2014) 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 32:634–6340PubMedCrossRef
63.
go back to reference Cook G, Liakopoulou E, Pearce R et al (2011) Factors influencing the outcome of a second autologous stem cell transplant (ASCT) in relapsed multiple myeloma: a study from the British Society of Blood and Marrow Transplantation Registry. Biol Blood Marrow Transplant 17:1638–1645PubMedCrossRef Cook G, Liakopoulou E, Pearce R et al (2011) Factors influencing the outcome of a second autologous stem cell transplant (ASCT) in relapsed multiple myeloma: a study from the British Society of Blood and Marrow Transplantation Registry. Biol Blood Marrow Transplant 17:1638–1645PubMedCrossRef
64.
go back to reference Mehta J, Singhal S (2007) High-dose chemotherapy and autologous hematopoietic stem cell transplantation in myeloma patients under the age of 65 years. Bone Marrow Transplant 40:1101–1114PubMedCrossRef Mehta J, Singhal S (2007) High-dose chemotherapy and autologous hematopoietic stem cell transplantation in myeloma patients under the age of 65 years. Bone Marrow Transplant 40:1101–1114PubMedCrossRef
65.
go back to reference Patriarca F, Einsele H, Spina F et al (2012) Allogeneic stem cell transplantation in multiple myeloma relapsed after autograft: a multicenter retrospective study based on donor availability. Biol Blood Marrow Transplant 18:617–626PubMedCrossRef Patriarca F, Einsele H, Spina F et al (2012) Allogeneic stem cell transplantation in multiple myeloma relapsed after autograft: a multicenter retrospective study based on donor availability. Biol Blood Marrow Transplant 18:617–626PubMedCrossRef
66.
go back to reference Kropff M, Baylon HG, Hillengass J et al (2012) Thalidomide versus dexamethasone for the treatment of relapsed and/or refractory multiple myeloma: results from OPTIMUM, a randomized trial. Haematologica 97:784–791PubMedCentralPubMedCrossRef Kropff M, Baylon HG, Hillengass J et al (2012) Thalidomide versus dexamethasone for the treatment of relapsed and/or refractory multiple myeloma: results from OPTIMUM, a randomized trial. Haematologica 97:784–791PubMedCentralPubMedCrossRef
67.
go back to reference Knopf KB, Duh MS, Lafeuille MH et al (2014) Meta-analysis of the efficacy and safety of bortezomib re-treatment in patients with multiple myeloma. Clin Lymphoma Myeloma Leuk 14:380–388PubMedCrossRef Knopf KB, Duh MS, Lafeuille MH et al (2014) Meta-analysis of the efficacy and safety of bortezomib re-treatment in patients with multiple myeloma. Clin Lymphoma Myeloma Leuk 14:380–388PubMedCrossRef
68.
go back to reference Madan S, Lacy MQ, Dispenzieri A et al (2011) Efficacy of retreatment with immunomodulatory drugs (IMiDs) in patients receiving IMiDs for initial therapy of newly diagnosed multiple myeloma. Blood 118:1763–1765PubMedCentralPubMedCrossRef Madan S, Lacy MQ, Dispenzieri A et al (2011) Efficacy of retreatment with immunomodulatory drugs (IMiDs) in patients receiving IMiDs for initial therapy of newly diagnosed multiple myeloma. Blood 118:1763–1765PubMedCentralPubMedCrossRef
69.
go back to reference Richardson PG, Sonneveld P, Schuster M et al (2007) Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood 110:3557–3560PubMedCrossRef Richardson PG, Sonneveld P, Schuster M et al (2007) Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood 110:3557–3560PubMedCrossRef
70.
go back to reference Richardson P, Jagannath S, Hussein M et al (2009) Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood 114:772–778PubMedCrossRef Richardson P, Jagannath S, Hussein M et al (2009) Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood 114:772–778PubMedCrossRef
71.
go back to reference Anagnostopoulos A, Weber D, Rankin K et al (2003) Thalidomide and dexamethasone for resistant multiple myeloma. Br J Haematol 121:768–771PubMedCrossRef Anagnostopoulos A, Weber D, Rankin K et al (2003) Thalidomide and dexamethasone for resistant multiple myeloma. Br J Haematol 121:768–771PubMedCrossRef
72.
go back to reference Dimopoulos MA, Chen C, Spencer A et al (2009) Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia 23:2147–2152PubMedCrossRef Dimopoulos MA, Chen C, Spencer A et al (2009) Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia 23:2147–2152PubMedCrossRef
73.
go back to reference San Miguel J, Weisel K, Moreau P et al (2013) Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol 14:1055–1066PubMedCrossRef San Miguel J, Weisel K, Moreau P et al (2013) Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol 14:1055–1066PubMedCrossRef
74.
go back to reference Stewart AK, Rajkumar SV, Dimopoulos MA et al (2015) Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 372:142–152PubMedCrossRef Stewart AK, Rajkumar SV, Dimopoulos MA et al (2015) Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 372:142–152PubMedCrossRef
75.
go back to reference San-Miguel JF, Hungria VT, Yoon SS et al (2014) Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol 15:1195–1206PubMedCrossRef San-Miguel JF, Hungria VT, Yoon SS et al (2014) Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol 15:1195–1206PubMedCrossRef
Metadata
Title
Current therapeutic strategies for multiple myeloma
Authors
Yoshihiro Torimoto
Motohiro Shindo
Katsuya Ikuta
Yutaka Kohgo
Publication date
01-06-2015
Publisher
Springer Japan
Published in
International Journal of Clinical Oncology / Issue 3/2015
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-015-0826-3

Other articles of this Issue 3/2015

International Journal of Clinical Oncology 3/2015 Go to the issue

Introduction to Review Articles

Recent advances in multiple myeloma

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine