Abstract
When the novel agents thalidomide, bortezomib and lenalidomide are administered to patients with myeloma in the context of clinical trials, they are associated with a significant improvement in response, progression-free survival and in some studies, overall survival (OS); however, their effect on the outcome of unselected myeloma patients has not been fully assessed. We compared the outcome of 1376 unselected patients with symptomatic myeloma, who started treatment before or after the introduction of thalidomide. The median OS in patients who started treatment after the introduction of novel agents increased by 12 months (48 vs 36 months, P<0.001). This improvement was more pronounced in patients ⩽70 years (from 39 to 74 months, P<0.001), but less evident in patients >70 years (from 26 to 33 months, P=0.27). In patients treated after the introduction of novel agents, the international staging system (ISS) could discriminate three groups with significantly different outcomes (5-year survival for ISS stage I, II and III was 66, 45 and 18%, respectively, P<0.001). ISS was also valid in patients who actually received upfront treatment with novel drugs (4-year survival rate was 85, 61 and 26% for ISS stage I, II and III patients, P=0.001).
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6633 patients from 27 randomized trials. J Clin Oncol 1998; 16: 3832–3842.
Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 1996; 335: 91–97.
Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J et al. International staging system for multiple myeloma. J Clin Oncol 2005; 23: 3412–3420.
Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565–1571.
Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003; 348: 2609–2617.
Richardson PG, Schlossman RL, Weller E, Hideshima T, Mitsiades C, Davies F et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002; 100: 3063–3067.
van Rhee F, Dhodapkar M, Shaughnessy Jr JD, Anaissie E, Siegel D, Hoering A et al. First thalidomide clinical trial in multiple myeloma: a decade. Blood 2008; 112: 1035–1038.
Rajkumar SV, Rosinol L, Hussein M, Catalano J, Jedrzejczak W, Lucy L et al. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol 2008; 26: 2171–2177.
Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR, Eastern Cooperative Oncology Group. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2006; 24: 431–436.
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.
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, 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.
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.
Brenner H, Gondos A, Pulte D . Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood 2008; 111: 2521–2526.
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.
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.
Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875–1883.
Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood 2007; 109: 3489–3495.
Shaughnessy Jr J, Zhan F, Barlogie B, Stewart AK . Gene expression profiling and multiple myeloma. Best Pract Res Clin Haematol 2005; 18: 537–552.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kastritis, E., Zervas, K., Symeonidis, A. et al. Improved survival of patients with multiple myeloma after the introduction of novel agents and the applicability of the International Staging System (ISS): an analysis of the Greek Myeloma Study Group (GMSG). Leukemia 23, 1152–1157 (2009). https://doi.org/10.1038/leu.2008.402
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/leu.2008.402
Keywords
This article is cited by
-
Autologous stem cell transplantation for multiple myeloma patients with chronic kidney disease: a safe and effective option
Bone Marrow Transplantation (2022)
-
Antibody–drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study
Blood Cancer Journal (2019)
-
Pretreatment 18F-FDG PET/CT combined with quantification of clonal circulating plasma cells as a potential risk model in patients with newly diagnosed multiple myeloma
European Journal of Nuclear Medicine and Molecular Imaging (2019)
-
Overall survival of transplant eligible patients with newly diagnosed multiple myeloma: comparative effectiveness analysis of modern induction regimens on outcome
Blood Cancer Journal (2018)
-
Evaluation of Revised International Staging System (R-ISS) for transplant-eligible multiple myeloma patients
Annals of Hematology (2018)