Skip to main content
Top
Published in: Drugs & Aging 10/2007

01-10-2007 | Therapy In Practice

Treatment Strategies in Elderly Patients with Multiple Myeloma

Current Status

Authors: Hang Quach, Dr H. Miles Prince, Linda Mileshkin

Published in: Drugs & Aging | Issue 10/2007

Login to get access

Abstract

Multiple myeloma (MM), a plasma cell malignancy, is a disorder of the elderly with an increasing prevalence as the average life expectancy increases. Survival remains unacceptably low in elderly patients with MM, in whom the gold standard of treatment has been, until recently, oral melphalan and prednisolone, which induces a response rate of approximately 50% and overall survival of <3 years. In the last 15 years, traditional treatment paradigms for elderly patients with MM have been challenged not only as a result of the change in what we define as ‘elderly’ but also as a result of the reduced morbidity and treatment-related mortality associated with high-dose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT), and the emergence of novel therapies including thalidomide, its immunomodulator drug derivative lenalidomide and the first-in-class proteasome inhibitor, bortezomib. In this review, we examine currently available data regarding the treatment of MM in the elderly population. Recent years have seen a paradigm shift in the standard of care of elderly patients with MM from oral melphalan and prednisolone to approaches including HDT with ASCT using intermediate-dose melphalan in selected elderly patients, and the evaluation of and incorporation of drugs such as thalidomide, bortezomib and lenalidomide. Importantly, we now have been able to change the traditional goal of palliation in the elderly group of patients to a more ambitious objective of achieving a complete response or a near complete response, in the hope that this will translate into improved progression-free survival, overall survival and quality of life.
Literature
1.
go back to reference Hideshima T, Bergsagel PL, Kueh WM, et al. Advances in biology of multiple myeloma: clinical applications. Blood 2004; 104: 607–18PubMedCrossRef Hideshima T, Bergsagel PL, Kueh WM, et al. Advances in biology of multiple myeloma: clinical applications. Blood 2004; 104: 607–18PubMedCrossRef
4.
go back to reference Morton ML, Wang SS, Devesa SS, et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 2006; 107(1): 265–75PubMedCrossRef Morton ML, Wang SS, Devesa SS, et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 2006; 107(1): 265–75PubMedCrossRef
5.
go back to reference Jantunen E. Autologous stem cell transplantation beyond 60 years of age. Bone Marrow Transplant 2006; 38: 1–6CrossRef Jantunen E. Autologous stem cell transplantation beyond 60 years of age. Bone Marrow Transplant 2006; 38: 1–6CrossRef
7.
go back to reference Blade J, Munoz M, Fontanillas M, et al. Treatment of multiple myeloma in the elderly people: long-term results in 178 patients. Age Ageing 1996; 25: 357–61PubMedCrossRef Blade J, Munoz M, Fontanillas M, et al. Treatment of multiple myeloma in the elderly people: long-term results in 178 patients. Age Ageing 1996; 25: 357–61PubMedCrossRef
8.
go back to reference Clavio M, Casciaro S, Gatti A, et al. Multiple myeloma in the elderly: clinical features and response to treatment in 113 patients. Haematologica 1996; 81: 238–44PubMed Clavio M, Casciaro S, Gatti A, et al. Multiple myeloma in the elderly: clinical features and response to treatment in 113 patients. Haematologica 1996; 81: 238–44PubMed
9.
go back to reference Corso A, Klersy C, Lazzarino M, et al. Multiple myeloma in younger patients: the role of age as prognostic factor. Ann Hematol 1998; 76: 67–72PubMedCrossRef Corso A, Klersy C, Lazzarino M, et al. Multiple myeloma in younger patients: the role of age as prognostic factor. Ann Hematol 1998; 76: 67–72PubMedCrossRef
10.
go back to reference Mileshkin L, Prince M. The adverse prognostic impact of advance age in multiple myeloma. Leuk Lymphoma 2005; 46(7): 951–66PubMedCrossRef Mileshkin L, Prince M. The adverse prognostic impact of advance age in multiple myeloma. Leuk Lymphoma 2005; 46(7): 951–66PubMedCrossRef
11.
12.
go back to reference Cohen HJ, Bartoloucci A. Age and the treatment of multiple myeloma: South Eastern Cancer Study Group experience. Am J Med 1985; 79: 316–24PubMedCrossRef Cohen HJ, Bartoloucci A. Age and the treatment of multiple myeloma: South Eastern Cancer Study Group experience. Am J Med 1985; 79: 316–24PubMedCrossRef
13.
go back to reference Anagnostopoulos A, Gika D, Symeonidis A, et al. Multiple myeloma in elderly patients: prognostic factors and outcome. Eur J Haematol 2005; 75: 370–5PubMedCrossRef Anagnostopoulos A, Gika D, Symeonidis A, et al. Multiple myeloma in elderly patients: prognostic factors and outcome. Eur J Haematol 2005; 75: 370–5PubMedCrossRef
14.
go back to reference Palva IP, Ahrenberg P, Ala-Harja K, et al. Treatment of multiple myeloma in old patients. Eur J Haematol 1989; 43: 328–31PubMed Palva IP, Ahrenberg P, Ala-Harja K, et al. Treatment of multiple myeloma in old patients. Eur J Haematol 1989; 43: 328–31PubMed
15.
go back to reference Smith A, Wisloff F, Samson D. Guidelines on the diagnosis and management of multiple myeloma 2005. Br J Haematol 2005; 132: 410–51CrossRef Smith A, Wisloff F, Samson D. Guidelines on the diagnosis and management of multiple myeloma 2005. Br J Haematol 2005; 132: 410–51CrossRef
16.
go back to reference Dimopoulos MA, Moulopoulos A, Smith T, et al. Risk of disease progression in asymptomatic multiple myeloma. Am J Med 1993; 94: 57–61PubMedCrossRef Dimopoulos MA, Moulopoulos A, Smith T, et al. Risk of disease progression in asymptomatic multiple myeloma. Am J Med 1993; 94: 57–61PubMedCrossRef
17.
18.
go back to reference Durie BG, Katz MS. Interactive computer program reveals current disease features and patterns of myeloma management [abstract]. Hematol J 2003; 4Suppl. 1: S181 Durie BG, Katz MS. Interactive computer program reveals current disease features and patterns of myeloma management [abstract]. Hematol J 2003; 4Suppl. 1: S181
19.
go back to reference Hjorth M, Hellquist L, Holmberg E, et al. Initial versus deferred melphalan-prednisolone therapy for asymptomatic multiple myeloma stage I: a randomised study. Eur J Haematol 1993; 50: 95–102PubMedCrossRef Hjorth M, Hellquist L, Holmberg E, et al. Initial versus deferred melphalan-prednisolone therapy for asymptomatic multiple myeloma stage I: a randomised study. Eur J Haematol 1993; 50: 95–102PubMedCrossRef
20.
go back to reference Riccardi A, Mora O, Tinelli C, et al. Long term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicenter randomised study. Cooperative Group Study and Treatment of Multiple Myeloma. Br J Cancer 2003; 82: 1254–60 Riccardi A, Mora O, Tinelli C, et al. Long term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicenter randomised study. Cooperative Group Study and Treatment of Multiple Myeloma. Br J Cancer 2003; 82: 1254–60
21.
22.
go back to reference Barlogie B, Jagannath S, Kesikan KR, et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999; 93: 55–65PubMed Barlogie B, Jagannath S, Kesikan KR, et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999; 93: 55–65PubMed
23.
go back to reference Davies FE, Forsyth PD, Rawstron AC, et al. The impact of attaining a minimal disease state after high-dose melphalan and autologous transplantation for multiple myeloma. Br J Haematol 2001; 112: 814–9PubMedCrossRef Davies FE, Forsyth PD, Rawstron AC, et al. The impact of attaining a minimal disease state after high-dose melphalan and autologous transplantation for multiple myeloma. Br J Haematol 2001; 112: 814–9PubMedCrossRef
24.
go back to reference Lahuerta JJ, Marinez-lopez J, De La Serna J, et al. Remission status defined by immunofixation vs electrophoresis after autologous transplantation has a major impact on outcome for multiple myeloma patients. Br J Haematol 2002; 109: 438–46CrossRef Lahuerta JJ, Marinez-lopez J, De La Serna J, et al. Remission status defined by immunofixation vs electrophoresis after autologous transplantation has a major impact on outcome for multiple myeloma patients. Br J Haematol 2002; 109: 438–46CrossRef
25.
go back to reference Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomised trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 1996; 335: 91–8PubMedCrossRef Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomised trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 1996; 335: 91–8PubMedCrossRef
26.
go back to reference Child AJ, Gareth JM, Faith ED, et al. High-dose chemotherapy with hematopoietic stem-rescue for multiple myeloma. N Engl J Med 2003; 348(19): 1875–9PubMedCrossRef Child AJ, Gareth JM, Faith ED, et al. High-dose chemotherapy with hematopoietic stem-rescue for multiple myeloma. N Engl J Med 2003; 348(19): 1875–9PubMedCrossRef
27.
go back to reference Levy V, Katsahian S, Fernand JP, et al. A meta-analysis on data from 575 patients with multiple myeloma randomly assigned to either high-dose therapy or conventional therapy. Medicine 2005; 84(4): 250–60PubMedCrossRef Levy V, Katsahian S, Fernand JP, et al. A meta-analysis on data from 575 patients with multiple myeloma randomly assigned to either high-dose therapy or conventional therapy. Medicine 2005; 84(4): 250–60PubMedCrossRef
28.
go back to reference Fernand J, Katsahian S, Marine D, et al. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol 2005; 36: 9227–33CrossRef Fernand J, Katsahian S, Marine D, et al. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol 2005; 36: 9227–33CrossRef
29.
go back to reference Palumbo A, Triolo S, Argentino C, et al. Dose intensive melphalan with stem cell support (MEL100) is superior to standard treatment in elderly myeloma patients. Blood 1999; 94: 1248–53PubMed Palumbo A, Triolo S, Argentino C, et al. Dose intensive melphalan with stem cell support (MEL100) is superior to standard treatment in elderly myeloma patients. Blood 1999; 94: 1248–53PubMed
30.
go back to reference Sirohi B, Powles R, Treleaven J, et al. The role of autologous transplantation in patients with multiple myeloma aged 65 years and over. Bone Marrow Transplant 2000; 25: 533–9PubMedCrossRef Sirohi B, Powles R, Treleaven J, et al. The role of autologous transplantation in patients with multiple myeloma aged 65 years and over. Bone Marrow Transplant 2000; 25: 533–9PubMedCrossRef
31.
go back to reference Guba SC, Vesole DH, Jagannath S, et al. Peripheral stem cell mobilization and engraftment in patients over 60 years of age. Bone Marrow Transplant 1997; 20: 1–3PubMedCrossRef Guba SC, Vesole DH, Jagannath S, et al. Peripheral stem cell mobilization and engraftment in patients over 60 years of age. Bone Marrow Transplant 1997; 20: 1–3PubMedCrossRef
32.
go back to reference Jantunen E, Kuittinen T, Penttila K, et al. High-dose melphalan (200mg/m2) supported by autologous stem cell transplantation is safe and effective in elderly (≥65 years) myeloma patients: comparison with younger patients treated within same protocol. Bone Marrow Transplant 2006; 37: 917–22PubMedCrossRef Jantunen E, Kuittinen T, Penttila K, et al. High-dose melphalan (200mg/m2) supported by autologous stem cell transplantation is safe and effective in elderly (≥65 years) myeloma patients: comparison with younger patients treated within same protocol. Bone Marrow Transplant 2006; 37: 917–22PubMedCrossRef
33.
go back to reference Mileshkin LR, Seymour JF, Wolf M, et al. Cardiovascular toxicity is increased, but manageable during high-dose chemotherapy and autologous peripheral blood stem cell transplantation for patients aged 60 years and older. Leuk Lymphoma 2005; 46(11): 1575–9PubMedCrossRef Mileshkin LR, Seymour JF, Wolf M, et al. Cardiovascular toxicity is increased, but manageable during high-dose chemotherapy and autologous peripheral blood stem cell transplantation for patients aged 60 years and older. Leuk Lymphoma 2005; 46(11): 1575–9PubMedCrossRef
34.
go back to reference Badros A, Barglogie B, Seigel E, et al. Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years. Br J Haematol 2001; 114: 600–7PubMedCrossRef Badros A, Barglogie B, Seigel E, et al. Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years. Br J Haematol 2001; 114: 600–7PubMedCrossRef
35.
go back to reference Prince HM, Imrie K, Stewart AK, et al. Peripheral blood progenitor cell collections in multiple myeloma: predictors and management of inadequate collections. Br J Haematol 1996; 93: 142–5PubMedCrossRef Prince HM, Imrie K, Stewart AK, et al. Peripheral blood progenitor cell collections in multiple myeloma: predictors and management of inadequate collections. Br J Haematol 1996; 93: 142–5PubMedCrossRef
36.
go back to reference Tricot G, Jagannath S, Vesole D, et al. Peripheral blood stem cell transplants for multiple myeloma: identification of favourable variables for rapid engraftment in 225 patients. Blood 1995; 85: 588–96PubMed Tricot G, Jagannath S, Vesole D, et al. Peripheral blood stem cell transplants for multiple myeloma: identification of favourable variables for rapid engraftment in 225 patients. Blood 1995; 85: 588–96PubMed
37.
go back to reference Scheid C, Draube A, Reiser M, et al. Using at least 5×106/kg CD34+ cells for autologous stem cell transplantation significantly reduces febrile complications and the use of antibiotics after transplantation. Bone Marrow Transplant 1999; 23: 1177–81PubMedCrossRef Scheid C, Draube A, Reiser M, et al. Using at least 5×106/kg CD34+ cells for autologous stem cell transplantation significantly reduces febrile complications and the use of antibiotics after transplantation. Bone Marrow Transplant 1999; 23: 1177–81PubMedCrossRef
38.
go back to reference Palumbo A, Bringhen S, Petrucci TM, et al. Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized control trial. Blood 2004; 104: 3052–7PubMedCrossRef Palumbo A, Bringhen S, Petrucci TM, et al. Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized control trial. Blood 2004; 104: 3052–7PubMedCrossRef
39.
go back to reference Alexanian R, Dimopoulos MA, Delasalle K, et al. Primary dexamethasone treatment of multiple myeloma. Blood 1992; 80: 887–90PubMed Alexanian R, Dimopoulos MA, Delasalle K, et al. Primary dexamethasone treatment of multiple myeloma. Blood 1992; 80: 887–90PubMed
40.
go back to reference Cavo M, Zamagni E, Tosi P, et al. First line therapy with thalidomide and dexamethasone in preparation for autologous stem cell transplantation for multiple myeloma. Haematologica 2004; 89: 826–31PubMed Cavo M, Zamagni E, Tosi P, et al. First line therapy with thalidomide and dexamethasone in preparation for autologous stem cell transplantation for multiple myeloma. Haematologica 2004; 89: 826–31PubMed
41.
go back to reference Cavo M, Zamagni E, Tosii P, et al. Superiority of thalidomide and dexamethasone over vincristine doxorubicin-dex-amethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood 2005; 106: 35–9PubMedCrossRef Cavo M, Zamagni E, Tosii P, et al. Superiority of thalidomide and dexamethasone over vincristine doxorubicin-dex-amethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood 2005; 106: 35–9PubMedCrossRef
42.
go back to reference Richardson P, Anderson K. Thalidomide and dexamethasone: a new standard of care for initial therapy in multiple myeloma. J Clin Oncol 2006; 24: 334–6PubMedCrossRef Richardson P, Anderson K. Thalidomide and dexamethasone: a new standard of care for initial therapy in multiple myeloma. J Clin Oncol 2006; 24: 334–6PubMedCrossRef
43.
go back to reference Barlogie B, Tricot G, Anaissie E, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006; 354: 1021–30PubMedCrossRef Barlogie B, Tricot G, Anaissie E, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006; 354: 1021–30PubMedCrossRef
44.
go back to reference The Myeloma Trialists’ Collaborative Group. Combination chemotherapy versus melphalan plus prednisolone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol 1998; 16: 3832–42 The Myeloma Trialists’ Collaborative Group. Combination chemotherapy versus melphalan plus prednisolone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol 1998; 16: 3832–42
45.
go back to reference Belch A, Shelley W, Bergsagel D, et al. A randomized trial of maintenance vs no maintenance melphalan and prednisolone in responding multiple myeloma patients. Br J Cancer 1988; 57: 94–9PubMedCrossRef Belch A, Shelley W, Bergsagel D, et al. A randomized trial of maintenance vs no maintenance melphalan and prednisolone in responding multiple myeloma patients. Br J Cancer 1988; 57: 94–9PubMedCrossRef
46.
go back to reference Carlson K, Martin J, Knudsen L. Toxicity in standard melphalan-prednisolone therapy among myeloma patients with renal failure: a retrospective analysis and recommendations for dose adjustments. Br J Haematol 2005; 128: 631–5PubMedCrossRef Carlson K, Martin J, Knudsen L. Toxicity in standard melphalan-prednisolone therapy among myeloma patients with renal failure: a retrospective analysis and recommendations for dose adjustments. Br J Haematol 2005; 128: 631–5PubMedCrossRef
47.
go back to reference Boccadoro M, Marmont F, Tribalto M, et al. Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisolone even in high risk patients. J Clin Oncol 1991; 9: 444–8PubMed Boccadoro M, Marmont F, Tribalto M, et al. Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisolone even in high risk patients. J Clin Oncol 1991; 9: 444–8PubMed
48.
go back to reference Turk BE, Jiang H, Lie JO. Binding of thalidomide to alpha-1-acid-glycoprotein may be involved in its inhibition of tumour necrosis factor alpha production. Proc Natl Acad Sci USA 1996; 93: 7552–6PubMedCrossRef Turk BE, Jiang H, Lie JO. Binding of thalidomide to alpha-1-acid-glycoprotein may be involved in its inhibition of tumour necrosis factor alpha production. Proc Natl Acad Sci USA 1996; 93: 7552–6PubMedCrossRef
49.
go back to reference Hideshima T, Chauhan D, Sima Y, et al. Thalidomide and its analogues overcome drug resistance of multiple myeloma cells to conventional therapy. Blood 2000; 96(9): 2943–50PubMed Hideshima T, Chauhan D, Sima Y, et al. Thalidomide and its analogues overcome drug resistance of multiple myeloma cells to conventional therapy. Blood 2000; 96(9): 2943–50PubMed
50.
go back to reference Rajkumar S, Dispenzieri A, Fonseca R, et al. Thalidomide for previously untreated indolent or smouldering multiple myeloma. Leukemia 2001; 15: 1274–6PubMedCrossRef Rajkumar S, Dispenzieri A, Fonseca R, et al. Thalidomide for previously untreated indolent or smouldering multiple myeloma. Leukemia 2001; 15: 1274–6PubMedCrossRef
51.
go back to reference Rajkumar V, Hayman S, Gertz A, et al. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 2002; 20: 4319–23PubMedCrossRef Rajkumar V, Hayman S, Gertz A, et al. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 2002; 20: 4319–23PubMedCrossRef
52.
go back to reference Rajkumar V, Blood E, Vesole D, et al. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by Eastern Cooperative Oncology Group. J Clin Oncol 2006; 24: 431–6PubMedCrossRef Rajkumar V, Blood E, Vesole D, et al. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by Eastern Cooperative Oncology Group. J Clin Oncol 2006; 24: 431–6PubMedCrossRef
53.
go back to reference Dingli D, Rajkumar SV, Nowakowski G, et al. Combination therapy with thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma not undergoing autologous stem cell transplant: a phase II trial. Haematologica 2005; 90(12): 1650–4PubMed Dingli D, Rajkumar SV, Nowakowski G, et al. Combination therapy with thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma not undergoing autologous stem cell transplant: a phase II trial. Haematologica 2005; 90(12): 1650–4PubMed
54.
go back to reference Weber D, Rankin K, Gavino M, et al. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol 2003; 21: 16–9PubMedCrossRef Weber D, Rankin K, Gavino M, et al. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol 2003; 21: 16–9PubMedCrossRef
55.
go back to reference Offidani M, Corvatta L, Maria-Novella P, et al. Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma. Blood 2006; 108: 2159–64PubMedCrossRef Offidani M, Corvatta L, Maria-Novella P, et al. Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma. Blood 2006; 108: 2159–64PubMedCrossRef
56.
go back to reference Palumbo A, Bringhen S, Caravito 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: 825–31PubMedCrossRef Palumbo A, Bringhen S, Caravito 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: 825–31PubMedCrossRef
57.
go back to reference Facon T, Mary JY, Harousseau J, et al. Superiority of melphalan-prednisolone (MP) + thalidomide (THAL) over MP and autologous stem cell transplantation in the treatment of newly diagnosed elderly patients with multiple myeloma: Intergroupe Fracophone du Myeloma [abstract]. J Clin Oncol 2006; 24(18S): 1 Facon T, Mary JY, Harousseau J, et al. Superiority of melphalan-prednisolone (MP) + thalidomide (THAL) over MP and autologous stem cell transplantation in the treatment of newly diagnosed elderly patients with multiple myeloma: Intergroupe Fracophone du Myeloma [abstract]. J Clin Oncol 2006; 24(18S): 1
58.
go back to reference Barlogie B, Diskan R, Eddlemon P, et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 2001; 98(2): 492–4PubMedCrossRef Barlogie B, Diskan R, Eddlemon P, et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 2001; 98(2): 492–4PubMedCrossRef
59.
go back to reference Prince HM, Schenkel B, Mileshkin L. An analysis of clinical trials assessing the efficacy and safety of single agent thalidomide in patients with relapsed or refractory multiple myeloma. Leuk Lymphoma 2007; 48(1): 46–55PubMedCrossRef Prince HM, Schenkel B, Mileshkin L. An analysis of clinical trials assessing the efficacy and safety of single agent thalidomide in patients with relapsed or refractory multiple myeloma. Leuk Lymphoma 2007; 48(1): 46–55PubMedCrossRef
60.
go back to reference Glasmacher A, Hahn C, Hoffmann F, et al. A systematic review of phase II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. Br J Haematol 2005; 132: 584–93CrossRef Glasmacher A, Hahn C, Hoffmann F, et al. A systematic review of phase II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. Br J Haematol 2005; 132: 584–93CrossRef
61.
go back to reference Kenealy M, Prince HM. Current status of new drugs for the treatment of patients with multiple myeloma. Int J Med 2006; 36: 1–9CrossRef Kenealy M, Prince HM. Current status of new drugs for the treatment of patients with multiple myeloma. Int J Med 2006; 36: 1–9CrossRef
62.
go back to reference Zangari M, Anaissie E, Barlogie B. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood 2001; 98: 1614–5PubMedCrossRef Zangari M, Anaissie E, Barlogie B. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood 2001; 98: 1614–5PubMedCrossRef
63.
go back to reference Rajkumar S. Thalidomide therapy and deep venous thrombosis in myeloma. Mayo Clin Proc 2005; 80: 1564–74 Rajkumar S. Thalidomide therapy and deep venous thrombosis in myeloma. Mayo Clin Proc 2005; 80: 1564–74
64.
65.
go back to reference Kumar S, Gertz MA, Dispenzieri A, et al. Response rate, durability of response and survival after thalidomide therapy for relapsed multiple myeloma. Mayo Clin Proc 2003; 78: 34–9PubMedCrossRef Kumar S, Gertz MA, Dispenzieri A, et al. Response rate, durability of response and survival after thalidomide therapy for relapsed multiple myeloma. Mayo Clin Proc 2003; 78: 34–9PubMedCrossRef
66.
go back to reference Mileshkin L, Stark R, Day B, et al. Development of neuropathy in patients with myeloma treated with thalidomide: patterns of occurrence and the role of electrophysiologic monitoring. J Clin Oncol 2006; 27: 4507–14CrossRef Mileshkin L, Stark R, Day B, et al. Development of neuropathy in patients with myeloma treated with thalidomide: patterns of occurrence and the role of electrophysiologic monitoring. J Clin Oncol 2006; 27: 4507–14CrossRef
67.
go back to reference Richardson P, Schlossmann R, Jagannath S, et al. Thalidomide for patients with relapsed multiple myeloma after high-dose chemotherapy and stem cell transplantation: results of an open-label multicenter phase 2 study of efficacy, toxicity and biological activity. Mayo Clin Proc 2004; 79(7): 875–82PubMedCrossRef Richardson P, Schlossmann R, Jagannath S, et al. Thalidomide for patients with relapsed multiple myeloma after high-dose chemotherapy and stem cell transplantation: results of an open-label multicenter phase 2 study of efficacy, toxicity and biological activity. Mayo Clin Proc 2004; 79(7): 875–82PubMedCrossRef
68.
go back to reference Mileshkin L, Prince HM. The troublesome toxicity of peripheral neuropathy with thalidomide. Leuk Lymphoma 2006; 47(11): 2276–9PubMedCrossRef Mileshkin L, Prince HM. The troublesome toxicity of peripheral neuropathy with thalidomide. Leuk Lymphoma 2006; 47(11): 2276–9PubMedCrossRef
69.
go back to reference Durie BG. Low-dose thalidomide in myeloma: efficacy and biologic significance. Semin Oncol 2002; 29(17S): 34–8PubMed Durie BG. Low-dose thalidomide in myeloma: efficacy and biologic significance. Semin Oncol 2002; 29(17S): 34–8PubMed
70.
go back to reference Palumbo A, Giaccone L, Bertola A, et al. Low dose thalidomide plus dexamethasone is an effective salvage therapy for advanced myeloma. Haematologica 2001; 86: 399–403PubMed Palumbo A, Giaccone L, Bertola A, et al. Low dose thalidomide plus dexamethasone is an effective salvage therapy for advanced myeloma. Haematologica 2001; 86: 399–403PubMed
71.
go back to reference Zhou S, Kestell P, Tingle MD, et al. Thalidomide in cancer treatment: a potential role in the elderly? Drugs Aging 2002; 19(2): 85–100PubMedCrossRef Zhou S, Kestell P, Tingle MD, et al. Thalidomide in cancer treatment: a potential role in the elderly? Drugs Aging 2002; 19(2): 85–100PubMedCrossRef
72.
go back to reference Fakhouri F, Guerraoui H, Presne C, et al. Thalidomide in patients with myeloma and renal failure. Br J Haematol 2004; 125: 96–7PubMedCrossRef Fakhouri F, Guerraoui H, Presne C, et al. Thalidomide in patients with myeloma and renal failure. Br J Haematol 2004; 125: 96–7PubMedCrossRef
73.
go back to reference Mazumder A, Jagannath S. Thalidomide and lenalidomide in multiple myeloma. Best Pract Res Clin Haematol 2006; 19(4): 769–80PubMedCrossRef Mazumder A, Jagannath S. Thalidomide and lenalidomide in multiple myeloma. Best Pract Res Clin Haematol 2006; 19(4): 769–80PubMedCrossRef
74.
go back to reference Anderson KC. Novel immunomodulatory therapies in the treatment of multiple myeloma. Oncology 2004; 18: 988–90PubMed Anderson KC. Novel immunomodulatory therapies in the treatment of multiple myeloma. Oncology 2004; 18: 988–90PubMed
75.
go back to reference Richardson P, Mitsiades C, Hideshima T, et al. Lenalidomide in multiple myeloma. Expert Rev Anticancer Ther 2006; 6(8): 1165–73PubMedCrossRef Richardson P, Mitsiades C, Hideshima T, et al. Lenalidomide in multiple myeloma. Expert Rev Anticancer Ther 2006; 6(8): 1165–73PubMedCrossRef
76.
go back to reference Dimopoulous M, Bweber D, Chen C, et al. Evaluating oral lenalidomide and dexamethasone versus placebo and dexamethasone in patients with relapsed or refractory multiple myeloma [abstract]. Haematologica 2005; 90Suppl. 2: 160 Dimopoulous M, Bweber D, Chen C, et al. Evaluating oral lenalidomide and dexamethasone versus placebo and dexamethasone in patients with relapsed or refractory multiple myeloma [abstract]. Haematologica 2005; 90Suppl. 2: 160
77.
go back to reference Rajkumar SV, Hayman SR, Martha Q, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005; 106: 4050–3PubMedCrossRef Rajkumar SV, Hayman SR, Martha Q, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005; 106: 4050–3PubMedCrossRef
78.
go back to reference Weber D. Two phase III randomised double blind, placebo-controlled trials of lenalidomide-dexamethasone vs dexamethasone for refractory or relapsed multiple myeloma. Presented at a special session titled: ImiDs-results of phase III studies in relapsed/refractory myeloma [online]. Available from URL: http://www.ASCO.org [Accessed 2006 Nov 24] Weber D. Two phase III randomised double blind, placebo-controlled trials of lenalidomide-dexamethasone vs dexamethasone for refractory or relapsed multiple myeloma. Presented at a special session titled: ImiDs-results of phase III studies in relapsed/refractory myeloma [online]. Available from URL: http://​www.​ASCO.​org [Accessed 2006 Nov 24]
79.
go back to reference Knight R, Delap JR, Zeldis BJ. Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med 2006; 354(19): 2079–80PubMedCrossRef Knight R, Delap JR, Zeldis BJ. Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med 2006; 354(19): 2079–80PubMedCrossRef
80.
go back to reference Rajkumar SV, Jacobus S, Callander N, et al. Phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group [abstract]. J Clin Oncol 2007; 25 (18 Suppl.): 8025a Rajkumar SV, Jacobus S, Callander N, et al. Phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group [abstract]. J Clin Oncol 2007; 25 (18 Suppl.): 8025a
81.
go back to reference Rajkumar SV. The role of lenalidomide in myeloma patients eligible for high dose therapy. Haematologica 2007; 92Suppl. 2: 30–1 Rajkumar SV. The role of lenalidomide in myeloma patients eligible for high dose therapy. Haematologica 2007; 92Suppl. 2: 30–1
82.
go back to reference Almond JB, Cohen GM. The proteasome: a novel target for cancer chemotherapy. Leukemia 2002; 16: 433–43PubMedCrossRef Almond JB, Cohen GM. The proteasome: a novel target for cancer chemotherapy. Leukemia 2002; 16: 433–43PubMedCrossRef
83.
go back to reference Hideshima T, Richardson P, Chauhan D, et al. The proteasome inhibitor PS-341 inhibits growth induces apoptosis, and over comes drug resistance in human multiple myeloma cells. Cancer Res 2001; 61: 3071–6PubMed Hideshima T, Richardson P, Chauhan D, et al. The proteasome inhibitor PS-341 inhibits growth induces apoptosis, and over comes drug resistance in human multiple myeloma cells. Cancer Res 2001; 61: 3071–6PubMed
84.
go back to reference Jagannath S, Durie B, Wolf J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 2005; 129: 776–83PubMedCrossRef Jagannath S, Durie B, Wolf J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 2005; 129: 776–83PubMedCrossRef
85.
go back to reference Harousseau JL, Attal M, Leleu X, et al. Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM phase II study. Haematologica 2006; 91: 1498–505PubMed Harousseau JL, Attal M, Leleu X, et al. Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM phase II study. Haematologica 2006; 91: 1498–505PubMed
86.
go back to reference Oakervee HE, Popat R, Curry N, et al. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol 2005; 129: 755–62PubMedCrossRef Oakervee HE, Popat R, Curry N, et al. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol 2005; 129: 755–62PubMedCrossRef
87.
go back to reference Cavenagh JK, Curry N, Stec J, et al. PAD therapy (bortezomib, doxorubicin, and dexamethasone) for untreated multiple myeloma (MM) [abstract]. J Clin Oncol 2004; 22(14S): 6550a Cavenagh JK, Curry N, Stec J, et al. PAD therapy (bortezomib, doxorubicin, and dexamethasone) for untreated multiple myeloma (MM) [abstract]. J Clin Oncol 2004; 22(14S): 6550a
88.
go back to reference Mateos MV, Hernandez JM, Hernandez MT, et al. Bortezomib plus melphalan and prednisolone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood 2006; 108(7): 2165–72PubMedCrossRef Mateos MV, Hernandez JM, Hernandez MT, et al. Bortezomib plus melphalan and prednisolone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood 2006; 108(7): 2165–72PubMedCrossRef
89.
go back to reference Richardson P, Chanan-Khan A, Schlossman R, et al. Phase II trial of single agent bortezomib (Velcade) in patients with previously untreated multiple myeloma [abstract]. Blood 2004; 104(11): 336a Richardson P, Chanan-Khan A, Schlossman R, et al. Phase II trial of single agent bortezomib (Velcade) in patients with previously untreated multiple myeloma [abstract]. Blood 2004; 104(11): 336a
90.
go back to reference Richardson P, Chanan-Khan A, Schlossman N, et al. A multicenter phase II trial of bortezomib in patients with previously untreated multiple myeloma: efficacy with manageable toxicity in patients with unexpectedly high rates of baseline peripheral neuropathy [abstract]. Blood 2005; 106: 2548a Richardson P, Chanan-Khan A, Schlossman N, et al. A multicenter phase II trial of bortezomib in patients with previously untreated multiple myeloma: efficacy with manageable toxicity in patients with unexpectedly high rates of baseline peripheral neuropathy [abstract]. Blood 2005; 106: 2548a
91.
go back to reference Wang M, Delasalle K, Alexanian R, et al. Rapid control of previously untreated multiple myeloma with bortezomib-thalidomide-dexamethasone followed by early intensive therapy [abstract]. Blood 2005; 106: 784a Wang M, Delasalle K, Alexanian R, et al. Rapid control of previously untreated multiple myeloma with bortezomib-thalidomide-dexamethasone followed by early intensive therapy [abstract]. Blood 2005; 106: 784a
92.
go back to reference Greco AF, Spigel RD, Barton JH, et al. Weekly bortezomib in the treatment of patients (pts) wtih previously treated multiple myeloma: a phase II trial of the Minnie Pearl Cancer Research Network [abstract]. J Clin Oncol 2006; 24 (18 Suppl.): 7547a Greco AF, Spigel RD, Barton JH, et al. Weekly bortezomib in the treatment of patients (pts) wtih previously treated multiple myeloma: a phase II trial of the Minnie Pearl Cancer Research Network [abstract]. J Clin Oncol 2006; 24 (18 Suppl.): 7547a
93.
go back to reference Suvannasankha A, Smith A, Abonour R. Weekly bortezomib with or without glucocorticosteroids is effective in patients with relapsed or refractory multiple myeloma [abstract]. Blood 2005; 106: 2652a Suvannasankha A, Smith A, Abonour R. Weekly bortezomib with or without glucocorticosteroids is effective in patients with relapsed or refractory multiple myeloma [abstract]. Blood 2005; 106: 2652a
94.
go back to reference Moreau P, Coiteux C, Hulin T, et al. Prospective comparison of subcutaneous vs intravenous administration of bortezomib in patients with multiple myeloma: pharmacokinetics, efficacy and toxicity [abstract; poster no. 617]. XIth International Myeloma Workshop; 2007 Jun 25–30; Kos Island Moreau P, Coiteux C, Hulin T, et al. Prospective comparison of subcutaneous vs intravenous administration of bortezomib in patients with multiple myeloma: pharmacokinetics, efficacy and toxicity [abstract; poster no. 617]. XIth International Myeloma Workshop; 2007 Jun 25–30; Kos Island
95.
go back to reference Myeloma Trialists’ Collaborative Group. Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. Br J Haematol 2001; 113: 1020–34CrossRef Myeloma Trialists’ Collaborative Group. Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. Br J Haematol 2001; 113: 1020–34CrossRef
96.
go back to reference Cunningham D, Powles R, Malpas J, et al. A randomised trial of maintenance interferon following high-dose chemotherapy in multiple myeloma: long term follow up results. Br J Haematol 1998; 102: 495–502PubMedCrossRef Cunningham D, Powles R, Malpas J, et al. A randomised trial of maintenance interferon following high-dose chemotherapy in multiple myeloma: long term follow up results. Br J Haematol 1998; 102: 495–502PubMedCrossRef
97.
go back to reference Berenson JR, Lichtenstein A, Porter L, et al. Maintenance with alternate-day prednisolone improves survival in multiple myeloma patients. Blood 2002; 99: 3163–8PubMedCrossRef Berenson JR, Lichtenstein A, Porter L, et al. Maintenance with alternate-day prednisolone improves survival in multiple myeloma patients. Blood 2002; 99: 3163–8PubMedCrossRef
98.
go back to reference Stewart AK, Chen CI, Howson-Jan K, et al. Results of multicenter randomized phase II trial of thalidomide and prednisone maintenance therapy for multiple myeloma after autologous stem cell transplant. Clin Cancer Res 2004; 10: 8170–6PubMedCrossRef Stewart AK, Chen CI, Howson-Jan K, et al. Results of multicenter randomized phase II trial of thalidomide and prednisone maintenance therapy for multiple myeloma after autologous stem cell transplant. Clin Cancer Res 2004; 10: 8170–6PubMedCrossRef
99.
go back to reference Attal M, Harousseau JL, Leyvraz S, et al. Maintenance treatment with thalidomide after autologous transplantation for myeloma: final analysis of a prospective randomized study of the ‘Intergroupe Francophone du Myelome’ [abstract]. Blood 2005; 106: 1148a Attal M, Harousseau JL, Leyvraz S, et al. Maintenance treatment with thalidomide after autologous transplantation for myeloma: final analysis of a prospective randomized study of the ‘Intergroupe Francophone du Myelome’ [abstract]. Blood 2005; 106: 1148a
100.
go back to reference Spencer A, Prince M, Roberts A, et al. First analysis of the Australasian Leukaemia and Lymphoma Group (ALLG) trial of thalidomide and alternate day prednisolone following autologous stem cell transplantation (ASCT) for patients with multiple myeloma (ALLG MM6) [abstract]. Blood 2006; 108: 58a Spencer A, Prince M, Roberts A, et al. First analysis of the Australasian Leukaemia and Lymphoma Group (ALLG) trial of thalidomide and alternate day prednisolone following autologous stem cell transplantation (ASCT) for patients with multiple myeloma (ALLG MM6) [abstract]. Blood 2006; 108: 58a
101.
go back to reference Buzaid AC, Durie GM. Management of refractory myeloma: a review. J Clin Oncol 1998; 6: 889–905 Buzaid AC, Durie GM. Management of refractory myeloma: a review. J Clin Oncol 1998; 6: 889–905
102.
go back to reference Alexanian R, Salmon S, Gutterman J, et al. Chemoimmunotherapy for multiple myeloma. Cancer 1981; 47: 1923–9PubMedCrossRef Alexanian R, Salmon S, Gutterman J, et al. Chemoimmunotherapy for multiple myeloma. Cancer 1981; 47: 1923–9PubMedCrossRef
103.
go back to reference Barlogie B, Smith L, Alexanian R. Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med 1984; 310: 1353–6PubMedCrossRef Barlogie B, Smith L, Alexanian R. Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med 1984; 310: 1353–6PubMedCrossRef
104.
go back to reference Richardson P, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005; 352(24): 2487–98PubMedCrossRef Richardson P, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005; 352(24): 2487–98PubMedCrossRef
105.
go back to reference Weber D, Wang M, Chen C, et al. Lenalidomide plus high dose dexamethasone provides improved overall survival compared to high dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): results of 2 phase III studies (MM-009, MM-010) and subgroup analysis of patients with impaired renal function [abstract]. Blood 2006; 108: 3547a Weber D, Wang M, Chen C, et al. Lenalidomide plus high dose dexamethasone provides improved overall survival compared to high dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): results of 2 phase III studies (MM-009, MM-010) and subgroup analysis of patients with impaired renal function [abstract]. Blood 2006; 108: 3547a
106.
go back to reference Gertz MA, Lacy MQ, Inwards DJ, et al. Early harvest and late transplantation as an effective therapeutic strategy in myeloma. Bone Marrow Transplant 1999; 23: 221–6PubMedCrossRef Gertz MA, Lacy MQ, Inwards DJ, et al. Early harvest and late transplantation as an effective therapeutic strategy in myeloma. Bone Marrow Transplant 1999; 23: 221–6PubMedCrossRef
107.
go back to reference Singhal S, Mehta J, Desikan R, et al. Antitumour activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565–71PubMedCrossRef Singhal S, Mehta J, Desikan R, et al. Antitumour activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565–71PubMedCrossRef
108.
go back to reference Weber DM, Gavino M, Delasalle K, et al. Thalidomide alone or with dexamethasone for multiple myeloma [abstract]. Blood 1999; 94: 604a Weber DM, Gavino M, Delasalle K, et al. Thalidomide alone or with dexamethasone for multiple myeloma [abstract]. Blood 1999; 94: 604a
109.
go back to reference Dimopolous AM, Zervas K, Kouvatseas G, et al. Thalidomide and dexamethasone combination for refractory multiple myeloma. Ann Oncol 2001; 12: 991–5CrossRef Dimopolous AM, Zervas K, Kouvatseas G, et al. Thalidomide and dexamethasone combination for refractory multiple myeloma. Ann Oncol 2001; 12: 991–5CrossRef
110.
go back to reference Palumbo A, Bertola A, Falco P, et al. Efficacy of low-dose thalidomide and dexamethasone as first salvage regimen in multiple myeloma. Hematol J 2004; 5: 318–24PubMedCrossRef Palumbo A, Bertola A, Falco P, et al. Efficacy of low-dose thalidomide and dexamethasone as first salvage regimen in multiple myeloma. Hematol J 2004; 5: 318–24PubMedCrossRef
111.
go back to reference Anagnostopoulos A, Weber D, Rankin K, et al. Thalidomide and dexamethasone for resistant multiple myeloma. Br J Haematol 2003; 121: 768–71PubMedCrossRef Anagnostopoulos A, Weber D, Rankin K, et al. Thalidomide and dexamethasone for resistant multiple myeloma. Br J Haematol 2003; 121: 768–71PubMedCrossRef
112.
go back to reference Mileshkin L, Biagi JJ, Mitchell P, et al. Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age. Blood 2003; 102: 69–77PubMedCrossRef Mileshkin L, Biagi JJ, Mitchell P, et al. Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age. Blood 2003; 102: 69–77PubMedCrossRef
113.
go back to reference Yakoub-Agha I, Hulin C, Doyen L, et al. A multicenter prospective randomised study testing non inferiority of thalidomide 100mg/d as compared with 400mg/d in patients with refractory/relapsed multiple myeloma: first results of the final analysis of the IFM 0–02 study [abstract]. J Clin Oncol 2006; 24(18S): 7520a Yakoub-Agha I, Hulin C, Doyen L, et al. A multicenter prospective randomised study testing non inferiority of thalidomide 100mg/d as compared with 400mg/d in patients with refractory/relapsed multiple myeloma: first results of the final analysis of the IFM 0–02 study [abstract]. J Clin Oncol 2006; 24(18S): 7520a
114.
go back to reference Offidani M, Corvatta L, Marconi M, et al. Low-dose thalidomide with pegylated liposomal doxorubicin and high dose dexamethasone for relapsed/refractory multiple myeloma: a prospective, multicenter phase II study. Haematologica 2006; 91: 133–6PubMed Offidani M, Corvatta L, Marconi M, et al. Low-dose thalidomide with pegylated liposomal doxorubicin and high dose dexamethasone for relapsed/refractory multiple myeloma: a prospective, multicenter phase II study. Haematologica 2006; 91: 133–6PubMed
115.
go back to reference Moehler TM, Neben K, Benner A, et al. Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy. Blood 2001; 98: 3846–8PubMedCrossRef Moehler TM, Neben K, Benner A, et al. Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy. Blood 2001; 98: 3846–8PubMedCrossRef
116.
go back to reference Lee CK, Barlogie B, Munshi N, et al. DTP ACE: an effective novel combination chemotherapy with thalidomide for previously treated patients with myeloma. J Clin Oncol 2003; 21: 2732–9PubMedCrossRef Lee CK, Barlogie B, Munshi N, et al. DTP ACE: an effective novel combination chemotherapy with thalidomide for previously treated patients with myeloma. J Clin Oncol 2003; 21: 2732–9PubMedCrossRef
117.
go back to reference Durie BGM, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–73PubMedCrossRef Durie BGM, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–73PubMedCrossRef
118.
go back to reference Prince HM, Schenkel B, Mileshkin L. Assessing response rates in clinical trials of treatment for relapsed or refractory multiple myeloma: a study of bortezomib and thalidomide. Leukemia 2007; 21(4): 818–20PubMed Prince HM, Schenkel B, Mileshkin L. Assessing response rates in clinical trials of treatment for relapsed or refractory multiple myeloma: a study of bortezomib and thalidomide. Leukemia 2007; 21(4): 818–20PubMed
119.
go back to reference Richardson GP, Blood E, Mitsiades SC, et al. A randomised phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 2006; 108(10): 3458–64PubMedCrossRef Richardson GP, Blood E, Mitsiades SC, et al. A randomised phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 2006; 108(10): 3458–64PubMedCrossRef
120.
go back to reference Richardson PG, Jagannath S, Schlossman R, et al. A multi-center, randomised, phase 2 study to evaluate the efficacy and safety of 2 CDC-5013 dose regimens when used alone or in combination with dexamethasone (dex) for the treatment of relapsed or refractory multiple myeloma (MM) [abstract]. Blood 2003; 102: 825a Richardson PG, Jagannath S, Schlossman R, et al. A multi-center, randomised, phase 2 study to evaluate the efficacy and safety of 2 CDC-5013 dose regimens when used alone or in combination with dexamethasone (dex) for the treatment of relapsed or refractory multiple myeloma (MM) [abstract]. Blood 2003; 102: 825a
121.
go back to reference Chanan-Khan AA, Weber D, Dimopolous M, et al. Lenalidomide (L) in combination with dexamethasone (D) improves survival and time to progression in elderly patients (pts) with relapsed or refractory multiple myeloma [abstract]. Blood 2006; 108: 3551a Chanan-Khan AA, Weber D, Dimopolous M, et al. Lenalidomide (L) in combination with dexamethasone (D) improves survival and time to progression in elderly patients (pts) with relapsed or refractory multiple myeloma [abstract]. Blood 2006; 108: 3551a
122.
go back to reference Weber DM, Chen C, Nievizky R, et al. A multicenter randomized parallel group double blind placebo controlled study of lenalidomide plus dexamethasone versus dexamethasone alone in previously treated subjects with multiple myeloma [abstract]. Haematologica 2005; 90Suppl. 1: 155 Weber DM, Chen C, Nievizky R, et al. A multicenter randomized parallel group double blind placebo controlled study of lenalidomide plus dexamethasone versus dexamethasone alone in previously treated subjects with multiple myeloma [abstract]. Haematologica 2005; 90Suppl. 1: 155
123.
go back to reference Dimopoulos M, Spencer A, Attal M, et al. Study of lenalidomide plus dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma (MM): results of a phase 3 study (MM-010) [abstract]. Blood 2005; 106(11): 6a Dimopoulos M, Spencer A, Attal M, et al. Study of lenalidomide plus dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma (MM): results of a phase 3 study (MM-010) [abstract]. Blood 2005; 106(11): 6a
124.
go back to reference Celgene Corporation. Revlimid (lenalidomide) [package insert]. Summit (NJ): Celgene Corporation, 2006 Celgene Corporation. Revlimid (lenalidomide) [package insert]. Summit (NJ): Celgene Corporation, 2006
125.
go back to reference Lonial S, Knight R, Dimopoulos M, et al. Effect of LEN/DEX in MM in different age groups [poster]. Xlth International Myeloma Workshop; 2007 Jun 25–30; Kos Island Lonial S, Knight R, Dimopoulos M, et al. Effect of LEN/DEX in MM in different age groups [poster]. Xlth International Myeloma Workshop; 2007 Jun 25–30; Kos Island
126.
go back to reference Richardson P, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003; 348(26): 2609–17PubMedCrossRef Richardson P, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003; 348(26): 2609–17PubMedCrossRef
127.
go back to reference Jagannath S, Barlogie, B, Berenson J, et al. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol 2004; 127: 165–72PubMedCrossRef Jagannath S, Barlogie, B, Berenson J, et al. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol 2004; 127: 165–72PubMedCrossRef
128.
go back to reference Richardson P, Sonneveld P, Schuster M, et al. Bortezomib continues demonstrates superior efficacy compared with high-dose dexamethasone in relapsed multiple myeloma: updated results of the APEX trial [abstract]. Blood 2005; 106: 2547a Richardson P, Sonneveld P, Schuster M, et al. Bortezomib continues demonstrates superior efficacy compared with high-dose dexamethasone in relapsed multiple myeloma: updated results of the APEX trial [abstract]. Blood 2005; 106: 2547a
129.
go back to reference Prince HM, Adena M, Smith DK, et al. Efficacy of single-agent bortezomib vs. single-agent thalidomide in patients with relapsed or refractory multiple myeloma: a systematic comparison. Eur J Haematol 2007; 79: 93–9PubMedCrossRef Prince HM, Adena M, Smith DK, et al. Efficacy of single-agent bortezomib vs. single-agent thalidomide in patients with relapsed or refractory multiple myeloma: a systematic comparison. Eur J Haematol 2007; 79: 93–9PubMedCrossRef
130.
go back to reference Richardson P, Sonneveld P, Schuster M, et al. Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed myeloma [abstract]. J Clin Oncol 2005; 23(16S): 6533a Richardson P, Sonneveld P, Schuster M, et al. Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed myeloma [abstract]. J Clin Oncol 2005; 23(16S): 6533a
131.
go back to reference Jagannath S, Richardson P, Sonnoveld P, et al. Bortezomib appears to overcome poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials [abstract]. J Clin Oncol 2005; 23(16S): 6501a Jagannath S, Richardson P, Sonnoveld P, et al. Bortezomib appears to overcome poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials [abstract]. J Clin Oncol 2005; 23(16S): 6501a
132.
go back to reference Richardson P, Barlogie B, Berenson J, et al. Clinical factors predictive of outcome with bortezomib in patients with relapsed refractory multiple myeloma. Blood 2005; 106: 2977–81PubMedCrossRef Richardson P, Barlogie B, Berenson J, et al. Clinical factors predictive of outcome with bortezomib in patients with relapsed refractory multiple myeloma. Blood 2005; 106: 2977–81PubMedCrossRef
133.
go back to reference San Miguel J, Blade J, Boccadoro M, et al. A practical update on the use of bortezomib in the management of multiple myeloma. Oncologist 2006; 11: 51–61PubMedCrossRef San Miguel J, Blade J, Boccadoro M, et al. A practical update on the use of bortezomib in the management of multiple myeloma. Oncologist 2006; 11: 51–61PubMedCrossRef
134.
go back to reference Chanan-Khan AA, Sonneveld P, Schuster WM, et al. Analysis of varicella zoster virus reactivation among bortezomib-treated patients in the APEX study [abstract]. Blood 2006; 108: 3535a Chanan-Khan AA, Sonneveld P, Schuster WM, et al. Analysis of varicella zoster virus reactivation among bortezomib-treated patients in the APEX study [abstract]. Blood 2006; 108: 3535a
135.
go back to reference Peles S, Fisher NM, Devien SM, et al. Bortezomib when given pretransplant and once weekly as consolidation therapy following high dose chemotherapy leads to high rates of reactivation of varicella zoster virus [abstract]. Blood 2005; 106: 3237a Peles S, Fisher NM, Devien SM, et al. Bortezomib when given pretransplant and once weekly as consolidation therapy following high dose chemotherapy leads to high rates of reactivation of varicella zoster virus [abstract]. Blood 2005; 106: 3237a
136.
go back to reference Kenealy KM, Prince HM, Honemann D. Tumour lysis syndrome early after treatment with bortezomib for multiple myeloma. Pharmacotherapy 2006; 26: 1205–6PubMedCrossRef Kenealy KM, Prince HM, Honemann D. Tumour lysis syndrome early after treatment with bortezomib for multiple myeloma. Pharmacotherapy 2006; 26: 1205–6PubMedCrossRef
137.
go back to reference Schey SA, Cavenagh J, Johnson R, et al. An UK myeloma forum phase II study of thalidomide: long term follow-up and recommendations for treatment. Leuk Res 2003; 27: 909–14PubMedCrossRef Schey SA, Cavenagh J, Johnson R, et al. An UK myeloma forum phase II study of thalidomide: long term follow-up and recommendations for treatment. Leuk Res 2003; 27: 909–14PubMedCrossRef
138.
go back to reference Berenson J, Lichtenstein A, Porter L, et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. J Clin Oncol 1998; 16: 593–602PubMed Berenson J, Lichtenstein A, Porter L, et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. J Clin Oncol 1998; 16: 593–602PubMed
139.
go back to reference Rosen LS, Gordon D, Antonio BS, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patient with breast cancer or osteolytic lesions of multiple myeloma: a phase II double-blind comparative trial. Cancer J 2001; 7: 377–87PubMed Rosen LS, Gordon D, Antonio BS, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patient with breast cancer or osteolytic lesions of multiple myeloma: a phase II double-blind comparative trial. Cancer J 2001; 7: 377–87PubMed
140.
go back to reference McClosley EV, Dunn JA, Kanis JA, et al. Long term follow-up of a prospective double blind placebo-controlled randomized trail of clodronate in multiple myeloma. Br J Haematol 2001; 113: 1035–43CrossRef McClosley EV, Dunn JA, Kanis JA, et al. Long term follow-up of a prospective double blind placebo-controlled randomized trail of clodronate in multiple myeloma. Br J Haematol 2001; 113: 1035–43CrossRef
141.
go back to reference Green JR, Mulier K, Jaeggi KA. Preclinical pharmacology of CGP 42’446, a new potent heterocyclic bisphosphonate compound. J Bone Miner Res 1994; 9: 745–51PubMedCrossRef Green JR, Mulier K, Jaeggi KA. Preclinical pharmacology of CGP 42’446, a new potent heterocyclic bisphosphonate compound. J Bone Miner Res 1994; 9: 745–51PubMedCrossRef
142.
go back to reference Rosen LS, Gordon D, Kaminski M, et al. Long term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 2003; 98: 1735–44PubMedCrossRef Rosen LS, Gordon D, Kaminski M, et al. Long term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 2003; 98: 1735–44PubMedCrossRef
143.
go back to reference Kyle AR, Yee CG, Somerfield RM, et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 2007; 25: 2464–72PubMedCrossRef Kyle AR, Yee CG, Somerfield RM, et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 2007; 25: 2464–72PubMedCrossRef
144.
go back to reference Badros A, Weikel D, Salama A, et al. Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 2006; 24(6): 945–52PubMedCrossRef Badros A, Weikel D, Salama A, et al. Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 2006; 24(6): 945–52PubMedCrossRef
145.
go back to reference Seshardri T, Prince M, Bell D, et al. The Australian Cancer Anaemia Survey: a snapshot of anaemia in adult patients with cancer. Med J Aus 2005; 182(9): 453–7 Seshardri T, Prince M, Bell D, et al. The Australian Cancer Anaemia Survey: a snapshot of anaemia in adult patients with cancer. Med J Aus 2005; 182(9): 453–7
146.
go back to reference Birgegard G, Gascon P, Ludwig H. Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European CANCER ANAEMIA SURVEY. Eur J Haematol 2006; 77: 378–86PubMedCrossRef Birgegard G, Gascon P, Ludwig H. Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European CANCER ANAEMIA SURVEY. Eur J Haematol 2006; 77: 378–86PubMedCrossRef
147.
go back to reference Dammaccos F, Castoldi G, Rodjer S. Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma. Br J Haematol 2001; 113: 172–9CrossRef Dammaccos F, Castoldi G, Rodjer S. Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma. Br J Haematol 2001; 113: 172–9CrossRef
148.
go back to reference Hedenus M, Adriansson M, San Miguel J, et al. Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double blind, placebo controlled study. Br J Haematol 2003; 122: 394–403PubMedCrossRef Hedenus M, Adriansson M, San Miguel J, et al. Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double blind, placebo controlled study. Br J Haematol 2003; 122: 394–403PubMedCrossRef
149.
go back to reference Cazzola M, Messinger D, Battistell V, et al. Recombinant human erythropoietin in the anemia associated with multiple myeloma or non-Hodgkin’s lymphoma: dose finding and identification of predictors of response. Blood 1995; 86: 4446–53PubMed Cazzola M, Messinger D, Battistell V, et al. Recombinant human erythropoietin in the anemia associated with multiple myeloma or non-Hodgkin’s lymphoma: dose finding and identification of predictors of response. Blood 1995; 86: 4446–53PubMed
150.
go back to reference Harousseau JL, Jagannath S, Richardson P, et al. Bortezomib in combination with high-dose dexamethasone (HD dex) and erythropoietin (EPO) does not result in an increased risk of thromboembolic complications [abstract]. Blood 2006; 108: 3543a Harousseau JL, Jagannath S, Richardson P, et al. Bortezomib in combination with high-dose dexamethasone (HD dex) and erythropoietin (EPO) does not result in an increased risk of thromboembolic complications [abstract]. Blood 2006; 108: 3543a
151.
go back to reference Rizzo JD, Lichtin AE, Woolf SH, et al. Use of epoetin in patients with cancer: evidence based clinical practice guidelines of the American Society of Clinical Oncology and American Society of Hematology. J Clin Oncol 2002; 20: 4083–107PubMedCrossRef Rizzo JD, Lichtin AE, Woolf SH, et al. Use of epoetin in patients with cancer: evidence based clinical practice guidelines of the American Society of Clinical Oncology and American Society of Hematology. J Clin Oncol 2002; 20: 4083–107PubMedCrossRef
152.
go back to reference Henke M, Laszig R, Rube C, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 2003; 362: 1255–60PubMedCrossRef Henke M, Laszig R, Rube C, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 2003; 362: 1255–60PubMedCrossRef
153.
go back to reference Leyland-Jones B, Siemiglazov V, Pawlicki M, et al. Maintaining normal hemoglobin levels with epoietin alfa in mainly nonanaemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol 2005; 23: 5960–72PubMedCrossRef Leyland-Jones B, Siemiglazov V, Pawlicki M, et al. Maintaining normal hemoglobin levels with epoietin alfa in mainly nonanaemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol 2005; 23: 5960–72PubMedCrossRef
154.
go back to reference Khuri RF. Weighing the hazards of erythropoiesis stimulation in patients with cancer. N Engl J Med 2007; 356: 2445–8PubMedCrossRef Khuri RF. Weighing the hazards of erythropoiesis stimulation in patients with cancer. N Engl J Med 2007; 356: 2445–8PubMedCrossRef
155.
go back to reference Longmore DG. Do cancer cells express functional erythropoietic receptors? N Engl J Med 2007; 356: 2447PubMedCrossRef Longmore DG. Do cancer cells express functional erythropoietic receptors? N Engl J Med 2007; 356: 2447PubMedCrossRef
156.
go back to reference Morgan GI, Davies FE. Evolving treatment strategies for myeloma. Br J Cancer 2005; 92: 217–21PubMed Morgan GI, Davies FE. Evolving treatment strategies for myeloma. Br J Cancer 2005; 92: 217–21PubMed
Metadata
Title
Treatment Strategies in Elderly Patients with Multiple Myeloma
Current Status
Authors
Hang Quach
Dr H. Miles Prince
Linda Mileshkin
Publication date
01-10-2007
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 10/2007
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.2165/00002512-200724100-00004

Other articles of this Issue 10/2007

Drugs & Aging 10/2007 Go to the issue

Therapy In Practice

Getting Better, Getting Well

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.