New era in staging/treatment of multiple myeloma



Multiple myeloma (MM) is a malignant disease of plasma cells with characteristic immune deregulation and represents 1% of all malignant diseases. The disease is characterized by clonal proliferation of plasma cells which may produce excessive amounts of monoclonal immunoglobulins that can be detected in serum and urine. The current revolution in therapeutic advances in myeloma started with the introduction of thalidomide, guided by knowledge of the antiangiogenic properties of thalidomide and the recognition of relevance of bone marrow angiogenesis in myeloma. Further, the international staging system (ISS) is now a widely accepted prognostic staging system for multiple myeloma patients; however, its validity is controversial in the era of new therapeutic regimens. This article has reviewed the alternative staging system based on Hb and plasmacytoma and various classes of novel drugs that are being evaluated in the setting of myeloma based on their mechanisms as well as the current understanding of disease biology.

Keywords: Multiple myeloma; Staging/treatment; Bone marrow; International staging system; Therapeutic regimens

Copyright © 2015 by The American Society for BioMedicine and BM-Publisher, Inc.

Article citationReferencesFull-Text/PDFBecome reviewer
The citation data is computed by the following citation measuring services:

Google scholarcitedby


  1.  Li Junxun, Li Juan, Tong Xiuzhen, Ouyang Juan, Zeng Bohuang, and Liu Junru. Comparing five diagnostic criteria for multiple myeloma:a retrospective study of 227 cases. Tumori 2014;100(2):207-213.
  2. Dinner S, Witteles W, Witteles R, Lam A, Arai S, Lafayette R, George TI, Schrier SL, Liedtke M.The prognostic value of diagnosing concurrent multiple myeloma in immunoglobulin light chain amyloidosis. Br J Haematol 2013;161(3):367-72.
  3. Schönland SO, Bochtler T, Kristen AV, Ho AD, Hegenbart U. [Current diagnostic and therapy of light chain amyloidosis]. Pathologe 2009;30(3):205-11.
  4. Dinner S, Witteles W, Witteles R, Lam A, Arai S, Lafayette R, George TI, Schrier SL, Liedtke M. The prognostic value of diagnosing concurrent multiple myeloma in immunoglobulin light chain amyloidosis. Br J Haematol 2013 ;161(3):367-72.
  5. Derlin T, Bannas P. Imaging of multiple myeloma: Current concepts. World J Orthop. 2014 ;5(3):272-82.
  6. International Myeloma Working Group.Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749-757.
  7. Wu P, Davies FE, Boyd K, Thomas K, Dines S, Saso RM, Potter MN, Ethell ME, Shaw BE, Morgan GJ. The impact of extramedullary disease at presentation on the outcome of myeloma. Leuk Lymphoma 2009;50:230-235.
  8. Barlogie B, Tricot GJ, van Rhee F, Angtuaco E, Walker R, Epstein J, Shaughnessy JD, Jagannath S, Bolejack V, Gurley J. Long-term outcome results of the first tandem autotransplant trial for multiple myeloma. Br J Haematol 2006;135:158-164.
  9. Bladé J, Dimopoulos M, Rosiñol L, Rajkumar SV, Kyle RA. Smoldering (asymptomatic) multiple myeloma: current diagnostic criteria, new predictors of outcome, and follow-up recommendations. J Clin Oncol 2010;28:690-697.
  10. Bannas P, Kröger N, Adam G, Derlin T. [Modern imaging techniques in patients with multiple myeloma]. Rofo 2013;185:26-33.
  11. Nanni C, Rubello D, Zamagni E, Castellucci P, Ambrosini V, Montini G, Cavo M, Lodi F, Pettinato C, Grassetto G. 18F-FDG PET/CT in myeloma with presumed solitary plasmocytoma of bone. In Vivo 2008;22:513-517.
  12. Durie BG, Waxman AD, D'Agnolo A, Williams CM. Whole-body (18)F-FDG PET identifies high-risk myeloma. J Nucl Med 2002;43:1457-1463.
  13. Rahmouni A, Divine M, Mathieu D, Golli M, Dao TH, Jazaerli N, Anglade MC, Reyes F, Vasile N. Detection of multiple myeloma involving the spine: efficacy of fat-suppression and contrast-enhanced MR imaging. AJR Am J Roentgenol 1993;160:1049-1052.
  14. Hillengass J, Wasser K, Delorme S, Kiessling F, Zechmann C, Benner A, Kauczor HU, Ho AD, Goldschmidt H, Moehler TM. Lumbar bone marrow microcirculation measurements from dynamic contrast-enhanced magnetic resonance imaging is a predictor of event-free survival in progressive multiple myeloma. Clin Cancer Res 2007;13:475-481.
  15. Hillengass J, Bäuerle T, Bartl R, Andrulis M, McClanahan F, Laun FB, Zechmann CM, et al. Diffusion-weighted imaging for non-invasive and quantitative monitoring of bone marrow infiltration in patients with monoclonal plasma cell disease: a comparative study with histology. Br J Haematol 2011;153:721-728.
  16. Moulopoulos LA, Gika D, Anagnostopoulos A, Delasalle K, Weber D, Alexanian R, Dimopoulos MA. Prognostic significance of magnetic resonance imaging of bone marrow in previously untreated patients with multiple myeloma. Ann Oncol 2005;16:1824-1828.
  17. Moulopoulos LA, Dimopoulos MA, Alexanian R, Leeds NE, Libshitz HI. Multiple myeloma: MR patterns of response to treatment. Radiology 1994;193:441-446.
  18. Walker R, Barlogie B, Haessler J, Tricot G, Anaissie E, Shaughnessy JD, Epstein J, van Hemert R, Erdem E, Hoering A. Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. J Clin Oncol 2007;25:1121-1128.
  19. Fenchel M, Konaktchieva M, Weisel K, Kraus S, Claussen CD, Horger M. Response assessment in patients with multiple myeloma during antiangiogenic therapy using arterial spin labeling and diffusion-weighted imaging: a feasibility study. Acad Radiol 2010;17:1326-1333.
  20. Horger M, Weisel K, Horger W, Mroue A, Fenchel M, Lichy M. Whole-body diffusion-weighted MRI with apparent diffusion coefficient mapping for early response monitoring in multiple myeloma: preliminary results. AJR Am J Roentgenol 2011;196:W790-W795.
  21. Callander NS, Roodman GD. Myeloma bone disease. Semin Hematol 2001;38:276-285.
  22. Lin C, Ho CL, Ng SH, Wang PN, Huang Y, Lin YC, Tang TC, Tsai SF, Rahmouni A, Yen TC. (11)C-acetate as a new biomarker for PET/CT in patients with multiple myeloma: initial staging and postinduction response assessment. Eur J Nucl Med Mol Imaging 2014;41:41-49.
  23. Oriol A. Multiple myeloma with extramedullary disease. Adv Ther. 2011;28 Suppl 7:1-6.
  24. Bladé J, Fernández de Larrea C, Rosiñol L, Cibeira MT, Jiménez R, Powles R. Soft-tissue plasmacytomas in multiple myeloma: incidence, mechanisms of extramedullary spread, and treatment approach. J Clin Oncol. 2011;29(28):3805-12.
  25. Harousseau JL, Shaughnessy J Jr, Richardson P. Multiple myeloma. Hematology Am Soc Hematol Educ Program. 2004:237-56.
  26. Hussein MA. Modifications to therapy for multiple myeloma: pegylated liposomal Doxorubicin in combination with vincristine, reduced-dose dexamethasone, and thalidomide. Oncologist 2003;8 Suppl 3:39-45.
  27. Richardson P, Schlossman 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;79:875-882.
  28. Barlogie B, Desikan 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;98:492-494.
  29. Mitsiades N, Mitsiades CS, Poulaki V, et al. Biologic sequelae of nuclear factor-kappaB blockade in multiple myeloma: therapeutic applications. Blood 2002;99:4079-4086.
  30. Kroger N, Schilling G, Einsele H, et al. Deletion of chromosome b and 13q14 as detected by fluorescence in situ hybridization is a prognostic factor in patients with multiple myeloma who are receiving allogeneic dose-reduced stem cell transplantation. Blood 2004;103:4056-4061.
  31. Maloney DG, Molina AJ, Sahebi F, et al. Allografting with non myeloabaltive conditioning following cytoreductive autograft for the treatment of patients with multiple myeloma. Blood 2003;102:3447-3454.
  32. Lockhorst HM, Segeren CM, Verdonck LF, et al. Partially T-cell depleted allogeneic stem-cell transplantation for first-line treatment of multiple myeloma: a prospective evaluation of patients treated in the phase III study Hovon 24 MM. J Clin Oncol 2003;21:1728-1733.
  33. Moreau P, Facon T, Leleu X, et al. Recurrent 14q32 translocations determine the prognosis of multiple myeloma especially in patients receiving intensive chemotherapy. Blood 2002;100:1579-1583.
  34. 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.
  35. Barlogie B, Jagannath S, Desikan KR, et al. Total therapy with tandem transplant for newly diagnosed multiple myeloma. Blood 1999;93:55-65.
  36. Barlogie B, Shaughnessy J, Tricot G, et al. Treatment of multiple myeloma. Blood 2004;103:20-32.
  37. Shaughnessy J, Tian E, Sawyer J, et al. High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH. Blood 2000;96:1505-1511.
  38. Ross ME, Zhou X, Song G, et al. Classification of pediatric acute lymphoblastic leukemia by gene expression profiling. Blood 2003;102:2951-2959.
  39. Santra M, Zhan F, Tian E, Barlogie B, Shaughnessy J, Jr. A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript. Blood 2003;101:2374-2376.
  40. Zhan F, Hardin J, Kordsmeier B, et al. Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells. Blood 2002;99:1745-1757.
  41. Corradini P, Boccadoro M, Voena C, Pileri A. Evidence for a bone marrow B cell transcribing malignant plasma cell VDJ joined to C mu sequence in immunoglobulin (IgG)- and IgA-secreting multiple myelomas. J Exp Med 1993;178:1091-1096.
  42. Billadeau D, Ahmann G, Greipp P, Van Ness B. The bone marrow of multiple myeloma patients contains B cell populations at different stages of differentiation that are clonally related to the malignant plasma cell. J Exp Med 1993;178:1023-1031.

Who Can Become a Reviewer?
Any expert in the article's research field can become a reviewer with American Journal of Biomedicine. Editors might ask you to look at a specific aspect of an article,...

Find out more

Research Article
American Journal of BioMedicine 2015, Volume 3, Issue 4, pages 241–253
Received June 10, 2015; Accepted September; 11, 2015, Published October 15, 2015

How to cite this article
Shi EY, Liu WY, Wang FC. New era in staging/treatment of multiple myeloma. American Journal of BioMedicine 2015;3(4):241–253
Topic Review
1. Abstract
2. Keywords
3. Introduction
4. Discussion
5. References

Article metric