Abstract
The majority of newly diagnosed multiple myeloma patients are over 65 years and/or physically unfit, and, therefore, are not eligible for standard treatment with high-dose chemotherapy and stem cell transplantation. The treatment goals in these patients should be to ensure improvement in disease management and to prolong survival while ensuring quality of life. Until recently, treatment options for such patients were limited, but new treatment combinations based on the novel agents thalidomide, bortezomib and lenalidomide have improved outcomes and survival. Moreover, phase III data indicate that maintenance treatment with novel agents may contribute to extended progression-free survival; however, the optimal duration of long-term therapy has not yet been defined. The potential for novel treatment regimens to improve the adverse prognosis associated with high-risk cytogenetic profiles, such as deletion 17p, also requires further research. Elderly patients, particularly those over 75 years and the clinically vulnerable, require close monitoring and individualized, dose-modified regimens to improve tolerability and treatment efficacy, while maintaining quality of life.
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References
Brenner H, Gondos A, Pulte D . Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood 2009; 111: 2521–2526.
Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Altekruse SF et al. (eds) SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). National Cancer Institute: Bethesda, MD, http://seer.cancer.gov/csr/1975_2009_pops09/, based on the November 2011 SEER data submission, posted to the SEER website, 2012.
Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008; 111: 2516–2520.
Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Björkholm M . Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol 2007; 25: 1993–1999.
Palumbo A, Gay F . How to treat elderly patients with multiple myeloma: combination of therapy or sequencing. Hematology Am Soc Hematol Educ Program 2009, 566–577.
National Comprehensive Cancer Network. Guidelines for Multiple Myeloma. Version 1, 2011. Available at www.nccn.org.
Myeloma Trialists’ Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol 1998; 16: 3832–3842.
Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet 2007; 370: 1209–1218.
Hulin C, Facon T, Rodon P, Pegourie B, Benboubker L, Doyen C et al. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol 2009; 27: 3664–3670.
Waage A, Gimsing P, Fayers P, Abildgaard N, Ahlberg L, Björkstrand B et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood 2010; 116: 1405–1412.
San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M et al. Continued overall survival benefit after 5 years’ follow-up with bortezomib-melphalan-prednisone (VMP) versus melphalan-prednisone (MP) in patients with previously untreated multiple myeloma, and no increased risk of second primary malignancies: final results of the phase 3 VISTA trial. Blood 2011; 118: (abstract 476).
Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V 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: 825–831.
Palumbo A, Bringhen S, Liberati AM, Caravita T, Falcone A, Callea V et al. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood 2008; 112: 3107–3114.
Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H et al. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol 2010; 28: 3160–3166.
Beksac H, Haznedar R, Firati-Tuglutar T, Ozdogu H, Aydogdu I, Konuk N et al. Addition of thalidomide to oral melphalan/prednisone (MP) in patients with multiple myeloma: initial results of a randomized trial from the Turkish Myeloma Study Group. Blood 2009; 114: (abstract 1880).
Ludwig H, Hajek R, Tóthová E, Drach J, Adam Z, Labar B et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood 2009; 113: 3435–3442.
Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ et al. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood 2011; 118: 1231–1238.
San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008; 359: 906–917.
Mateos MV, Richardson PG, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol 2010; 28: 2259–2266.
Mateos MV, Oriol A, MartÃnez-López J, Gutiérrez N, Teruel AI, de Paz R et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 2010; 11: 934–941.
Palumbo A, Bringhen S, Rossi D, Cavalli M, Ria R, Gentilini S et al. Overall survival benefit for bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in newly diagnosed multiple myeloma patients. Blood 2012; 120: 200.
Zonder JA, Crowley J, Hussein MA, Bolejack V, Moore Sr DF, Whittenberger BF et al. Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood 2010; 116: 5838–5841.
Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 2010; 11: 29–37.
Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012; 366: 1759–1769.
Fayers PM, Palumbo A, Hulin C, Waage A, Wijermans P, Beksaç M et al. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood 2011; 118: 1239–1247.
Palumbo A, Waage A, Hulin C, Beksac M, Zweegman S, Gay F et al. Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials. Haematologica 2013; 98: 87–94.
Harousseau JL, Palumbo A, Richardson PG, Schlag R, Dimopoulos MA, Shpilberg O et al. Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone. Blood 2010; 116: 3743–3750.
Palumbo A, Sezer O, Kyle R, Miguel JS, Orlowski RZ, Moreau P et al. International Myeloma Working Group guidelines for the management of multiple myeloma patients ineligible for standard high-dose chemotherapy with autologous stem cell transplantation. Leukemia 2009; 23: 1716–1730.
Mateos MV, Oriol A, MartÃnez-López J, Gutiérrez N, Teruel AI, López de la GuÃa A et al. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood 2012; 120: 2581–2588.
Gay F, Vincent Rajkumar S, Falco P, Kumar S, Dispenzieri A, Petrucci MT et al. Lenalidomide plus dexamethasone vs. lenalidomide plus melphalan and prednisone: a retrospective study in newly diagnosed elderly myeloma. Eur J Haematol 2010; 85: 200–208.
Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010; 116: 679–686.
Jakubowiak AJ, Griffith KA, Reece DE, Hofmeister CC, Lonial S, Zimmerman TM et al. Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial. Blood 2011; 118: 535–543.
Niesvizky R, Jayabalan DS, Christos PJ, Furst JR, Naib T, Ely S et al. BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma. Blood 2008; 111: 1101–1109.
Kastritis E, Palumbo A, Dimopoulos MA . Treatment of relapsed/refractory multiple myeloma. Semin Hematol 2009; 46: 143–157.
Lipinski E, Cremer FW, Ho AD, Goldschmidt H, Moos M . Molecular monitoring of the tumor load predicts progressive disease in patients with multiple myeloma after high-dose therapy with autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 2001; 28: 957–962.
Morgan GJ, Gregory WM, Davies FE, Bell SE, Szubert AJ, Brown JM et al. The role of thalidomide maintenance therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood 2012; 119: 7–15.
Munshi NC, Anderson KC, Bergsagel PL, Shaughnessy J, Palumbo A, Durie B et al. Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood 2011; 117: 4696–4700.
Palumbo A, Falco P, Corradini P, Falcone A, Di Raimondo F, Giuliani N et al. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA--Italian Multiple Myeloma Network. J Clin Oncol 2007; 25: 4459–4465.
Kapoor P, Kumar S, Fonseca R, Lacy MQ, Witzig TE, Hayman SR et al. Impact of risk stratification on outcome among patients with multiple myeloma receiving initial therapy with lenalidomide and dexamethasone. Blood 2009; 114: 518–521.
Kumar SK, Lacy MQ, Hayman SR, Stewart K, Buadi FK, Allred J et al. Lenalidomide, cyclophosphamide and dexamethasone (CRd) for newly diagnosed multiple myeloma: results from a phase 2 trial. Am J Hematol 2011; 86: 640–645.
Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 2008; 22: 414–423.
Delforge M, Bladé J, Dimopoulos MA, Facon T, Kropff M, Ludwig H et al. Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. Lancet Oncol 2010; 11: 1086–1095.
Dimopoulos MA, Palumbo A, Attal M, Beksaç M, Davies FE, Delforge M et al. Optimizing the use of lenalidomide in relapsed or refractory multiple myeloma: consensus statement. Leukemia 2011; 25: 749–760.
Acknowledgements
We thank Shanthi Jayawardena, PhD, and Eva Polk, PhD (Excerpta Medica), for their medical writing assistance. Editorial support in the preparation of this manuscript was funded by Celgene Corporation. M-VM and JFS-M were fully responsible for all content and editorial decisions for this manuscript.
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M-VM has served on the speakers’ bureau for Onyx Pharmaceuticals, Centocor Ortho-Biotech (Janssen), Millennium and Celgene Corporation, and has received honoraria from Janssen-Cilag, Celgene Corporation and Novartis. JFS-M has received compensation as a scientific advisory board member of Millennium, Celgene Corporation, Janssen-Cilag, Novartis and Bristol-Myers Squibb. JFS-M has also received consulting fees from Janssen-Cilag, Millennium.
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San Miguel, J., Mateos, MV. Advances in treatment for newly diagnosed multiple myeloma patients ineligible for autologous stem cell transplantation. Leukemia Suppl 2 (Suppl 1), S21–S27 (2013). https://doi.org/10.1038/leusup.2013.5
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DOI: https://doi.org/10.1038/leusup.2013.5