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.
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References
Hideshima T, Bergsagel PL, Kueh WM, et al. Advances in biology of multiple myeloma: clinical applications. Blood 2004; 104: 607–18
Ries LAG, Harkins D, Krapcho M, et al. SEER cancer statistic review [online]. Available from URL: http://www.seer.cancer.gov [Accessed 2006 Nov 25]
American Cancer Society [online]. Available from URL: http://www.cancer.org [Accessed 2007 Jul 25]
Morton ML, Wang SS, Devesa SS, et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 2006; 107(1): 265–75
Jantunen E. Autologous stem cell transplantation beyond 60 years of age. Bone Marrow Transplant 2006; 38: 1–6
Penson TR, Daniels JK, Lynch Jr TJ. Too old to care? Oncologist 2004; 9: 343–52
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: 357–61
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: 238–44
Corso A, Klersy C, Lazzarino M, et al. Multiple myeloma in younger patients: the role of age as prognostic factor. Ann Hematol 1998; 76: 67–72
Mileshkin L, Prince M. The adverse prognostic impact of advance age in multiple myeloma. Leuk Lymphoma 2005; 46(7): 951–66
Froom P, Quitt M, Aghai E. Multiple myeloma in the geriatric patient. Cancer 1990; 66: 965–7
Cohen HJ, Bartoloucci A. Age and the treatment of multiple myeloma: South Eastern Cancer Study Group experience. Am J Med 1985; 79: 316–24
Anagnostopoulos A, Gika D, Symeonidis A, et al. Multiple myeloma in elderly patients: prognostic factors and outcome. Eur J Haematol 2005; 75: 370–5
Palva IP, Ahrenberg P, Ala-Harja K, et al. Treatment of multiple myeloma in old patients. Eur J Haematol 1989; 43: 328–31
Smith A, Wisloff F, Samson D. Guidelines on the diagnosis and management of multiple myeloma 2005. Br J Haematol 2005; 132: 410–51
Dimopoulos MA, Moulopoulos A, Smith T, et al. Risk of disease progression in asymptomatic multiple myeloma. Am J Med 1993; 94: 57–61
Kyle RA, Rajkumar S. Drug therapy: multiple myeloma. N Engl J Med 2004; 351(18): 1860–73
Durie BG, Katz MS. Interactive computer program reveals current disease features and patterns of myeloma management [abstract]. Hematol J 2003; 4Suppl. 1: S181
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: 95–102
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
Harousseau JL, Attal M. High dose therapy in multiple myeloma. Hematol J 2003; 4: 163–70
Barlogie B, Jagannath S, Kesikan KR, et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999; 93: 55–65
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: 814–9
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: 438–46
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: 91–8
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): 1875–9
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): 250–60
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: 9227–33
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: 1248–53
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: 533–9
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: 1–3
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: 917–22
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): 1575–9
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: 600–7
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: 142–5
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: 588–96
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: 1177–81
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: 3052–7
Alexanian R, Dimopoulos MA, Delasalle K, et al. Primary dexamethasone treatment of multiple myeloma. Blood 1992; 80: 887–90
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: 826–31
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: 35–9
Richardson P, Anderson K. Thalidomide and dexamethasone: a new standard of care for initial therapy in multiple myeloma. J Clin Oncol 2006; 24: 334–6
Barlogie B, Tricot G, Anaissie E, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006; 354: 1021–30
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
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: 94–9
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: 631–5
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: 444–8
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: 7552–6
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): 2943–50
Rajkumar S, Dispenzieri A, Fonseca R, et al. Thalidomide for previously untreated indolent or smouldering multiple myeloma. Leukemia 2001; 15: 1274–6
Rajkumar V, Hayman S, Gertz A, et al. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 2002; 20: 4319–23
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: 431–6
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): 1650–4
Weber D, Rankin K, Gavino M, et al. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol 2003; 21: 16–9
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: 2159–64
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: 825–31
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
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): 492–4
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): 46–55
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: 584–93
Kenealy M, Prince HM. Current status of new drugs for the treatment of patients with multiple myeloma. Int J Med 2006; 36: 1–9
Zangari M, Anaissie E, Barlogie B. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood 2001; 98: 1614–5
Rajkumar S. Thalidomide therapy and deep venous thrombosis in myeloma. Mayo Clin Proc 2005; 80: 1564–74
Honemann D, Prince HM. Myeloma, thalidomide and thrombosis. Leuk Lymphoma 2006; 47(11): 2273–5
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: 34–9
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: 4507–14
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): 875–82
Mileshkin L, Prince HM. The troublesome toxicity of peripheral neuropathy with thalidomide. Leuk Lymphoma 2006; 47(11): 2276–9
Durie BG. Low-dose thalidomide in myeloma: efficacy and biologic significance. Semin Oncol 2002; 29(17S): 34–8
Palumbo A, Giaccone L, Bertola A, et al. Low dose thalidomide plus dexamethasone is an effective salvage therapy for advanced myeloma. Haematologica 2001; 86: 399–403
Zhou S, Kestell P, Tingle MD, et al. Thalidomide in cancer treatment: a potential role in the elderly? Drugs Aging 2002; 19(2): 85–100
Fakhouri F, Guerraoui H, Presne C, et al. Thalidomide in patients with myeloma and renal failure. Br J Haematol 2004; 125: 96–7
Mazumder A, Jagannath S. Thalidomide and lenalidomide in multiple myeloma. Best Pract Res Clin Haematol 2006; 19(4): 769–80
Anderson KC. Novel immunomodulatory therapies in the treatment of multiple myeloma. Oncology 2004; 18: 988–90
Richardson P, Mitsiades C, Hideshima T, et al. Lenalidomide in multiple myeloma. Expert Rev Anticancer Ther 2006; 6(8): 1165–73
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
Rajkumar SV, Hayman SR, Martha Q, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005; 106: 4050–3
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]
Knight R, Delap JR, Zeldis BJ. Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med 2006; 354(19): 2079–80
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. The role of lenalidomide in myeloma patients eligible for high dose therapy. Haematologica 2007; 92Suppl. 2: 30–1
Almond JB, Cohen GM. The proteasome: a novel target for cancer chemotherapy. Leukemia 2002; 16: 433–43
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: 3071–6
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: 776–83
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: 1498–505
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: 755–62
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
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): 2165–72
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 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
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
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
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
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
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: 1020–34
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: 495–502
Berenson JR, Lichtenstein A, Porter L, et al. Maintenance with alternate-day prednisolone improves survival in multiple myeloma patients. Blood 2002; 99: 3163–8
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: 8170–6
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
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
Buzaid AC, Durie GM. Management of refractory myeloma: a review. J Clin Oncol 1998; 6: 889–905
Alexanian R, Salmon S, Gutterman J, et al. Chemoimmunotherapy for multiple myeloma. Cancer 1981; 47: 1923–9
Barlogie B, Smith L, Alexanian R. Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med 1984; 310: 1353–6
Richardson P, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005; 352(24): 2487–98
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
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: 221–6
Singhal S, Mehta J, Desikan R, et al. Antitumour activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565–71
Weber DM, Gavino M, Delasalle K, et al. Thalidomide alone or with dexamethasone for multiple myeloma [abstract]. Blood 1999; 94: 604a
Dimopolous AM, Zervas K, Kouvatseas G, et al. Thalidomide and dexamethasone combination for refractory multiple myeloma. Ann Oncol 2001; 12: 991–5
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: 318–24
Anagnostopoulos A, Weber D, Rankin K, et al. Thalidomide and dexamethasone for resistant multiple myeloma. Br J Haematol 2003; 121: 768–71
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: 69–77
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
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: 133–6
Moehler TM, Neben K, Benner A, et al. Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy. Blood 2001; 98: 3846–8
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: 2732–9
Durie BGM, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–73
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): 818–20
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): 3458–64
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
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
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
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
Celgene Corporation. Revlimid (lenalidomide) [package insert]. Summit (NJ): Celgene Corporation, 2006
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
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): 2609–17
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: 165–72
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
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: 93–9
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
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
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: 2977–81
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: 51–61
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
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
Kenealy KM, Prince HM, Honemann D. Tumour lysis syndrome early after treatment with bortezomib for multiple myeloma. Pharmacotherapy 2006; 26: 1205–6
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: 909–14
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: 593–602
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: 377–87
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: 1035–43
Green JR, Mulier K, Jaeggi KA. Preclinical pharmacology of CGP 42’446, a new potent heterocyclic bisphosphonate compound. J Bone Miner Res 1994; 9: 745–51
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: 1735–44
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: 2464–72
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): 945–52
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
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: 378–86
Dammaccos F, Castoldi G, Rodjer S. Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma. Br J Haematol 2001; 113: 172–9
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: 394–403
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: 4446–53
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
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: 4083–107
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: 1255–60
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: 5960–72
Khuri RF. Weighing the hazards of erythropoiesis stimulation in patients with cancer. N Engl J Med 2007; 356: 2445–8
Longmore DG. Do cancer cells express functional erythropoietic receptors? N Engl J Med 2007; 356: 2447
Morgan GI, Davies FE. Evolving treatment strategies for myeloma. Br J Cancer 2005; 92: 217–21
Acknowledgements
No sources of funding were used to assist in the preparation of this review. Dr Prince has acted as a consultant to Celgene and Janssen-Cilag and has been the recipient of a research grant from Celgene. The other authors have no potential conflicts of interest that are directly relevant to the content of this review.
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Quach, H., Prince, H.M. & Mileshkin, L. Treatment Strategies in Elderly Patients with Multiple Myeloma. Drugs Aging 24, 829–850 (2007). https://doi.org/10.2165/00002512-200724100-00004
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DOI: https://doi.org/10.2165/00002512-200724100-00004