The Korean journal of internal medicine

  • 제28권3호
  • /
  • Pages.263-273
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  • 2013
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  • 1226-3303(pISSN)
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  • 2005-6648(eISSN)
대한내과학회 (The Korean Association of Internal Medicine)
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Diagnosis and therapy of multiple myeloma

  • Palumbo, Antonio (Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliera Citta della Salute e della Scienza di Torino) ;
  • Cerrato, Chiara (Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliera Citta della Salute e della Scienza di Torino)
  • 발행 : 2013.05.01
⟨ 이전 논문 다음 논문 ⟩

초록

Many advances in the treatment of multiple myeloma have been made due to the use of transplantation and the introduction of novel agents including thalidomide, lenalidomide, and bortezomib. The first step is recognizing the symptoms and starting prompt treatment. Different strategies should be selected for young and elderly subjects. Young patients are commonly eligible for transplantation, which is now considered the standard approach for this setting, and various inductions therapies containing novel agents are available before transplantation. Elderly patients are usually not eligible for transplantation, and gentler approaches with new drugs combinations are used for their treatment.

키워드

참고문헌

  1. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med 2011;364:1046-1060. https://doi.org/10.1056/NEJMra1011442
  2. Altekruse SF, Kosary CL, Krapcho M, et al. SEER cancer statistics review, 1975-2007 [Internet]. Bethesda (MD): National Cancer Institute, 2010 [cited 2012 Nov 26]. Available from: http://seer.cancer.gov/csr/1975_2007/index. html.
  3. Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Bjorkholm 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. https://doi.org/10.1200/JCO.2006.09.0100
  4. Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood 2008;111:2521-2526. https://doi.org/10.1182/blood-2007-08-104984
  5. Durie BG, Kyle RA, Belch A, et al. Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation. Hematol J 2003;4:379-398. https://doi.org/10.1038/sj.thj.6200312
  6. Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467-1473. https://doi.org/10.1038/sj.leu.2404284
  7. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009;23:3-9. https://doi.org/10.1038/leu.2008.291
  8. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78:21-33. https://doi.org/10.4065/78.1.21
  9. Eleutherakis-Papaiakovou V, Bamias A, Gika D, et al. Renal failure in multiple myeloma: incidence, correlations, and prognostic signif icance. Leuk Lymphoma 2007;48:337-341. https://doi.org/10.1080/10428190601126602
  10. 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;77:378-386. https://doi.org/10.1111/j.1600-0609.2006.00739.x
  11. Nucci M, Anaissie E. Infections in patients with multiple myeloma in the era of high-dose therapy and novel agents. Clin Infect Dis 2009;49:1211-1225. https://doi.org/10.1086/605664
  12. Dispenzieri A, Kyle R, Merlini G, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009;23:215-224. https://doi.org/10.1038/leu.2008.307
  13. Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group molecular classif ication of multiple myeloma: spotlight review. Leukemia 2009;23:2210-2221. https://doi.org/10.1038/leu.2009.174
  14. Terpos E, Moulopoulos LA, Dimopoulos MA. Advances in imaging and the management of myeloma bone disease. J Clin Oncol 2011;29:1907-1915. https://doi.org/10.1200/JCO.2010.32.5449
  15. Zamagni E, Nanni C, Patriarca F, et al. A prospective comparison of 18F-f luorodeoxyglucose positron emission tomography-computed tomography, magnetic resonance imaging and whole-body planar radiographs in the assessment of bone disease in newly diagnosed multiple myeloma. Haematologica 2007;92:50-55. https://doi.org/10.3324/haematol.10554
  16. Dimopoulos M, Kyle R, Fermand JP, et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood 2011;117:4701-4705. https://doi.org/10.1182/blood-2010-10-299529
  17. Durie BG, Salmon SE. A clinical staging system for multiple myeloma: correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975;36:842-854. https://doi.org/10.1002/1097-0142(197509)36:3<842::AID-CNCR2820360303>3.0.CO;2-U
  18. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol 2005;23:3412-3420. https://doi.org/10.1200/JCO.2005.04.242
  19. Avet-Loiseau H, Durie BG, Cavo M, et al. Combining fluorescent in situ hybridization data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group collaborative project. Leukemia 2013;27:711-717. https://doi.org/10.1038/leu.2012.282
  20. Snozek CL, Katzmann JA, Kyle RA, et al. Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia 2008;22:1933-1937. https://doi.org/10.1038/leu.2008.171
  21. Mulligan G, Mitsiades C, Bryant B, et al. Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib. Blood 2007;109:3177-3188. https://doi.org/10.1182/blood-2006-09-044974
  22. Shaughnessy JD Jr, Zhan F, Burington BE, et al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood 2007;109:2276-2284. https://doi.org/10.1182/blood-2006-07-038430
  23. Zamagni E, Patriarca F, Nanni C, et al. Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation. Blood 2011;118:5989-5995. https://doi.org/10.1182/blood-2011-06-361386
  24. Kumar SK, Dingli D, Lacy MQ, et al. Autologous stem cell transplantation in patients of 70 years and older with multiple myeloma: results from a matched pair analysis. Am J Hematol 2008;83:614-617. https://doi.org/10.1002/ajh.21191
  25. Attal M, Harousseau JL, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003;349:2495-2502. https://doi.org/10.1056/NEJMoa032290
  26. Cavo M, Tosi P, Zamagni E, et al. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol 2007;25:2434-2441. https://doi.org/10.1200/JCO.2006.10.2509
  27. Segeren CM, Sonneveld P, van der Holt B, et al. Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study. Blood 2003;101:2144-2151. https://doi.org/10.1182/blood-2002-03-0889
  28. Goldschmidt H. Single vs. double high-dose therapy in multiple myeloma: second analysis of the GMMG-HD2 trial [abstract]. Haematologica 2005;90(Suppl 1):38.
  29. Barlogie B, Attal M, Crowley J, et al. Long-term followup of autotransplantation trials for multiple myeloma: update of protocols conducted by the intergroupe francophone du myelome, southwest oncology group, and university of arkansas for medical sciences. J Clin Oncol 2010;28:1209-1214. https://doi.org/10.1200/JCO.2009.25.6081
  30. Harousseau JL, Attal M, Avet-Loiseau H. The role of complete response in multiple myeloma. Blood 2009;114:3139-3146. https://doi.org/10.1182/blood-2009-03-201053
  31. Chanan-Khan AA, Giralt S. Importance of achieving a complete response in multiple myeloma, and the impact of novel agents. J Clin Oncol 2010;28:2612-2624. https://doi.org/10.1200/JCO.2009.25.4250
  32. Ladetto M, Pagliano G, Ferrero S, et al. Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol 2010;28:2077-2084. https://doi.org/10.1200/JCO.2009.23.7172
  33. Fermand JP, Alberti C, Marolleau JP. Single versus tandem high dose therapy (HDT) supported with autologous blood stem cell (ABSC) transplantation using unselected or CD34-enriched ABSC: results of a two by two designed randomized trial in 230 young patients with multiple myeloma (MM). Hematol J 2003;4 Suppl 1:S59.
  34. Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR. 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. https://doi.org/10.1200/JCO.2005.03.0221
  35. Lokhorst HM, Schmidt-Wolf I, Sonneveld P, et al. Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma. Haematologica 2008;93:124-127. https://doi.org/10.3324/haematol.11644
  36. Morgan GJ, Davies FE, Gregory WM, et al. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica 2012;97:442-450. https://doi.org/10.3324/haematol.2011.043372
  37. Rajkumar SV, Jacobus S, Callander NS, 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. https://doi.org/10.1016/S1470-2045(09)70284-0
  38. Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010;116:679-686. https://doi.org/10.1182/blood-2010-02-268862
  39. Kumar S, Flinn I, Richardson PG, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood 2012;119:4375-4382. https://doi.org/10.1182/blood-2011-11-395749
  40. Kumar SK, Flinn I, Noga SJ, et al. Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study. Leukemia 2010;24:1350-1356. https://doi.org/10.1038/leu.2010.116
  41. Jagannath S, Durie BG, Wolf JL, et al. Extended followup of a phase 2 trial of bortezomib alone and in combination with dexamethasone for the frontline treatment of multiple myeloma. Br J Haematol 2009;146:619-626. https://doi.org/10.1111/j.1365-2141.2009.07803.x
  42. 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;91:1498-1505.
  43. Rosinol L, Oriol A, Mateos MV, et al. Phase II PETHEMA trial of alternating bortezomib and dexamethasone as induction regimen before autologous stemcell transplantation in younger patients with multiple myeloma: efficacy and clinical implications of tumor response kinetics. J Clin Oncol 2007;25:4452-4458. https://doi.org/10.1200/JCO.2007.12.3323
  44. Harousseau JL, Attal M, Avet-Loiseau H, et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol 2010;28:4621-4629. https://doi.org/10.1200/JCO.2009.27.9158
  45. Sonneveld P, Schmidt-Wolf IG, van der Holt B, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMGHD4 trial. J Clin Oncol 2012;30:2946-2955. https://doi.org/10.1200/JCO.2011.39.6820
  46. Cavo M, Tacchetti P, Patriarca F, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet 2010;376:2075-2085. https://doi.org/10.1016/S0140-6736(10)61424-9
  47. Reeder CB, Reece DE, Kukreti V, et al. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia 2009;23:1337-1341. https://doi.org/10.1038/leu.2009.26
  48. 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. https://doi.org/10.1200/JCO.1998.16.12.3832
  49. Ludwig H, Hajek R, Tothova E, et al. Thalidomidedexamethasone compared with melphalan-predniso lone in elderly patients with multiple myeloma. Blood 2009;113:3435-3442. https://doi.org/10.1182/blood-2008-07-169565
  50. Facon T, Mary JY, Hulin C, 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. https://doi.org/10.1016/S0140-6736(07)61537-2
  51. Hulin C, Facon T, Rodon P, 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. https://doi.org/10.1200/JCO.2008.21.0948
  52. Beksac M, Haznedar R, Firatli-Tuglular T, et al. Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group. Eur J Haematol 2011;86:16-22. https://doi.org/10.1111/j.1600-0609.2010.01524.x
  53. Waage A, Gimsing P, Fayers P, et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood 2010;116:1405-1412. https://doi.org/10.1182/blood-2009-08-237974
  54. Wijermans P, Schaafsma M, Termorshuizen F, 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. https://doi.org/10.1200/JCO.2009.26.1610
  55. Palumbo A, Bringhen S, Liberati AM, 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. https://doi.org/10.1182/blood-2008-04-149427
  56. Fayers PM, Palumbo A, Hulin C, 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. https://doi.org/10.1182/blood-2011-03-341669
  57. Palumbo A, Waage A, Hulin C, 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. https://doi.org/10.3324/haematol.2012.067058
  58. Morgan GJ, Davies FE, Gregory WM, et al. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood 2011;118:1231-1238. https://doi.org/10.1182/blood-2011-02-338665
  59. Palumbo A, Hajek R, Delforge M, et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 2012;366:1759-1769. https://doi.org/10.1056/NEJMoa1112704
  60. Kumar SK, Lacy MQ, Hayman SR, 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. https://doi.org/10.1002/ajh.22053
  61. San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008;359:906-917. https://doi.org/10.1056/NEJMoa0801479
  62. Mateos MV, Richardson PG, Schlag R, 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. https://doi.org/10.1200/JCO.2009.26.0638
  63. Mateos MV, Oriol A, Martinez-Lopez J, 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. https://doi.org/10.1016/S1470-2045(10)70187-X
  64. Palumbo A, Bringhen S, Rossi D, et al. Bortezomibmelphalan- prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol 2010;28:5101-5109. https://doi.org/10.1200/JCO.2010.29.8216
  65. Bringhen S, Larocca A, Rossi D, et al. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood 2010;116:4745-4753. https://doi.org/10.1182/blood-2010-07-294983

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