Multiple myeloma: the disease and its treatment


  • Meenakshi Gupta Department of Pharmacology, Sri Guru Ram Das Institute of Medical sciences and Research, Vallah, Amritsar-143001, Punjab, India
  • Rana Arun Gopal Krishan Pal Department of Pathology, Genesis Institute of Dental Sciences & Research, Ferozepur-152002, Punjab, India
  • Deepika Tikoo Department of Pharmacology, Sri Guru Ram Das Institute of Medical sciences and Research, Vallah, Amritsar-143001, Punjab, India


Myeloma, Thalidomide, Lenalidomide, Bortezomib, Therapy


Multiple myeloma represents a malignant proliferation of plasma cells derived from a single clone. The tumor, its products and the host response to it result in a number of organ dysfunctions and symptoms of bone pain, fracture, anemia, hypercalcemia, susceptibility to infection, neurologic symptoms, clotting abnormalities and manifestations of hyperviscosity. The cause of myeloma remains unexplained but it is associated with few occupations, inflammatory conditions, autoimmune illnesses, viral infections and genetic heterogeneity. Direct interaction between multiple myeloma cells and bone marrow cells activates pleiotropic signalling pathways that mediate growth, survival, migration of multiple myeloma cells and also resistance to chemotherapy. Although myeloma remains incurable, but the use of novel drugs like thalidomide, lenalidomide and bortezomib have resulted in a paradigm change in the therapy of myeloma. Their inclusion in current multiple myeloma treatment regimens have extended median overall survival especially in younger patient population. Recent advances in the molecular genetics have provided opportunities to design highly specific inhibitors of signal transduction pathways that may enhance the efficacy of standard chemotherapy drugs by reducing or altering the pathways associated with cell survival. Despite therapeutic advances, multiple myeloma ultimately relapses and remains an incurable disease. Current research goals are to further increase our knowledge, to identify additional targeted therapies, and to reduce adverse effects and improve response rate. This review focuses on recent clinical advancement in ant myeloma strategies with additional discussion dedicated to emerging drugs that may prove beneficial to patients with this disease.


Munshi NC, Longo DL, Anderson KC: Plasma Cell Disorders. In: Fausi AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison’s Principles of Internal Medicine, 17th ed., Ch. 106 New York: Mc Graw Hill; 2008. P700-6.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics 2008. CA Cancer J Clin 2008;58:71-96.

Hirabayashi Y, Katanoda K. Comparison of time trends in multiple myeloma incidence (1973–1997) in East Asia, Europe and United States from Cancer Incidence in Five Continents, Vols IV–VIII. Jpn J Clin Oncol 2008;38:720-1.

Kumar L, Vikram P, Kochupillai V. Recent advances in the management of multiple myeloma. Natl Med J India 2006;19:80-9.

Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics 2001. CA Cancer J Clin 2001;51:15-36.

Harousseau JL, Moreau P. Autologous hematopoietic stem-cell transplantation for multiple myeloma. N Engl J Med 2009;360:2645-54.

Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78:21-33.

Kyle RA. Multiple myeloma: an odyssey of discovery. Br J Haematol 2000;111:1035-44.

Rajkumar SV, Kyle RA. Plasma cell disorders. In: Goldman L, Ausiello D. Cecil Textbook of Medicine. 23nd ed., Ch 198. Philadelphia: WB Saunders. p1426-37.

Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med 2004;351:1860-73.

Cerhan JR, Cantor KP, Williamson K , Lynch CF, Torner JC, Burmeister LF. Cancer mortality among lowa farmers: recent results, time trends, and lifestyle factors (United states). Cancer causes Control 1998;9:311-9.

Lewis EB. Leukemia, multiple myeloma, and aplastic anaemia in American radiologists. Science1963;142:1492-4.

Gregersen H, Pedersen G, Svendsen N, Thulstrup AM, Sørensen HT, Schønheyder HC. Multiple myeloma following an episode of community- acquired pneumococcal bacteraemia or meningitis. APMIS 2001;109:797-800.

Grulich AE, Wan X, Law MG, Coates M, Kaldor JM. Risk of cancer in people with AIDS. AIDS 1999;13:839-43.

Gharagozloo S, Khoshnoodi J, Shokri F. Hepatitis C virus infections in patients with essential mixed cryoglobulinemia, multiple myeloma and chronic lymphocytic leukemia. Pathol Oncol Res 2001;7:135-9.

An J, Lichtenstein AK, Brent G, Rettig MB. The Kaposi sarcoma-associated herpesvirus (KSHV) induces cellular interleukin 6 expression: role of KSHV latency-associated nuclear antigen and the API response element. Blood 2002;99:649-54.

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 Mye´lome. Blood 2007; 109: 3489-95.

Grass S, Preuss KD, Ahlgrimm M, Fadle N, Regitz E, Pfoehler C et al. Association of a dominantly inherited hyperphosphorylated paraprotein target with sporadic and familial multiple myeloma and monoclonal gammopathy of undetermined significance: A case control study. Lancet Oncol 2009;10:950-6.

Vachon CM, Kyle RA, Therneau TM, Foreman BJ, Larson DR, Colby CL et al. Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance. Blood 2009;114:785-90.

Lynch HT, Ferrara K, Barlogie B, Coleman EA, Lynch JF, Weisenburger D et al. Familial myeloma. N Engl J Med 2008;359:152-7.

Kyle RA, Therneau TM, Rajkumar SV , Offord JR, Larson DR, Plevak MF, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med 2002;346:564-9.

Witzig TE. Oncogenic events. The comprehensive guide to Baniff: Understanding the VIIIth international myeloma workshop, Published by International Myeloma Foundation, USA.

Klein B, Zhang XG, Jourdan M, Content J, Houssiau F, Aarden L, et al. Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6. Blood 1989;73:517-26.

Puthier D, Bataille R, Amiot M. IL-6 up-regulates mcl-1in human myeloma cells through JAK/STAT rather than RAS/MAP kinase pathway. Eur J Immunol 1999;29:3945-50.

French JD, Tschumper RC, Jelinek DF. Dissection of the signaling requirements of interleukin-6-stimulated myeloma cell growth. Acta Oncol 2000;39:777-81.

Catlett-Falcone R, Landowski TH, Oshiro MM,Turkson J, Levitzki A, Savino R, et al. Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 1999;10:105-15.

Dispenzieri A, Lacy MQ and Greipp PR: Multiple myeloma. In:Greer JP, Rodgers GM, Foerster J, Paraskevas F. Lukens JN, Glader B. Wintrobe,s Clinical hematology, 11th ed.,Ch. 98 Philadelphia: Lippincott Williams & Wilkins;2004. P2583-636.

Dankbar B, Padro T, Leo R, Feldmann B, Kropff M, Mesters RM, et al. Vascular and endothelial growth factor and interleukin-6 in paracrine tumor- stromal cell interactions in multiple myeloma. Blood 2000;95:2630-6.

Sezer O, Jakob C, Eucker J, Niemöller K, Gatz F, Wernecke K, et al. Serum levels of the angiogenic cytokines basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in multiple myeloma. Eur J Haematol 2001;66:83-8.

Jelinek DF, Witzig TE, Arendt BK. A role for insulin like growth factor in the regulation of IL-6-responsive human myeloma cell line growth. J Immunol 1997;159:487-96.

Ge NL, Rudikoff S. Insulin-like growth factor I is a dual effector of multiple myeloma cell growth. Blood 2000;96:2856-61.

Hargreaves RM, Lea JR, Griffiths H, Faux JA, Holt JM, Reid C et al. Immunological factors and risk of infection in plateau phase myeloma. J Clin Pathol 1995;48:260-6.

Nucci M, Anaissie E. Infections in patients with multiple myeloma in the era of high dose therapy and novel agents. Clin Infect Dis 2009;49:1211-25.

Zhou Y, Barlogie B, Shaughnessy JD Jr. The molecular characterization and clinical management of multiple myeloma in the post-genome era. Leukemia 2009;23:1941-56.

Dewald GW, Therneau T, Larson D, Lee YK, Fink S, Smoley S et al. Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma. Blood 2005;106:3553-8.

Caers J, Vande broek I, De Raeve H, Michaux L, Trullemans F, Schots R et al. Multiple myeloma: an update on diagnosis and treatment. Eur J Haematol 2008;81:329-43.

Katzmann JA, Clark RJ, Abraham RS, et al. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 2002;48:1437-44.

Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders:A report of the International Myeloma Working Group. Br J Haematol 2003;121:749-57.

Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance and smouldering multiple myeloma: Emphasis on risk factors for progression. Br J Haematol 2007;139:730-43.

Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007;356:2582-90.

Kyle RA. Long-term survival in multiple myeloma. N Engl J Med. 1983;308:314-6.

Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D, et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999;93:55-65.

Desikan R, Barlogie B, Sawyer J, Ayers D, Tricot G, Badros A, et al. Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 2000;95:4008-10.

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;36:842-54.

Kyle RA. Prognostic factors in multiple myeloma. Stem Cells 1995;13:56-63.

Rapoport BL, Falkson HC, Falkson G. Prognostic factors affecting the survival of patients with multiple myeloma: a retrospective analysis of 86 patients. S Afr Med J 1991;79:65-7.

Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol 2005;23:3412-20.

Gertz MA, Lacy MQ, Dispensieri A, Greipp PR, Litzow MR, Henderson KJ et al. Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy. Blood 2005;106:2837-40.

Zhan F, Huang Y, Colla S, Stewart JP, Hanamura I, Gupta S et al. The molecular classification of multiple myeloma. Blood 2006;108:2020-8.

Hjorth M, Hellquist L, Holmberg E, Magnusson B, Rödjer S, Westin J. Initial versus deferred melphalan-prednione therapy for asymptomatic multiple myeloma stage I: a randomized study. Myeloma group of Western Sweden. Eur J Haematol 1993;50:95-102.

Riccardi A, Mora O, Tinelli C Valentini D, Brugnatelli S, Spanedda R, et al. Long term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of disease: a multicentre randomized study. Cooperative Group of study and treatment of multiple myeloma. Br J Cancer 2000;82:1254-60.

Harousseau JL. Role of stem cell transplantation in multiple myeloma. Hematol Oncol Clin North Am 2007;21:1157-74.

Goldschmidt H, Hegenbart U, Wallmeier M, Hohaus S, Haas R. Factors influencing collection of peripheral blood progenitor cells following high-dose cyclophosphamide and granulocyte colony-stimulating factor in patients with multiple myeloma. Br J Haematol 1997;98:736-44.

Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol 1990;33:86-9.

U.S Food and Drug Administration. FDA Approves Thalomid (thalidomide) to Treat Multiple Myeloma. Available at Accessed 25 October 2012.

Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR et al. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 2002;20:4319-23.

Cavo M, Zamagni E, Tosi P, Cellini C, Cangini D, Tacchetti 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, Tosi P, Tacchetti P, Cellini C, Cangini D, et al. Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood 2005;106:35-9.

Fermand J-P, Jaccard A, Macro M, et al. A randomized comparison of dexamethasone + thalidomide (Dex/Thal) vs Dex + Placebo (Dex/P) in patients (pts) with relapsing multiple myeloma (MM). Blood 2006;108:3563.

Macro M, Divine M, Uzunhan Y, Jaccard A, Bouscary D, Leblond V, et al. Dexamethasone+Thalidomide (Dex/Thal) compared to VAD as a pre-transplant treatment in newly diagnosed ,multiple myeloma (MM): A Randomized Trial. Blood 2006;108:57.

Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR. Eastern Cooperative Oncology Group. Phase III trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed myeloma: a clinical trial coordinated by the Eastern Cooperative Group. J Clin Oncol 2006;24:431-6.

Palumbo A, Falco P. New drugs in the therapy of multiple myeloma. Rev Bras Hematol 2008;30:1-7.

Palumbo A, Facon T, Sonneveld P, Bladè J, Offidani M, Gay F et al. Thalidomide for treatment of multiple myeloma: 10 years later. Blood 2008;111:3968-77.

Gay F, Palumbo A. Multiple myeloma: Management of adverse events. Med Oncol 2009;27:646-53.

Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005;106:4050-3.

Rajkumar SV, Jacobus S, Callander N, Fonseca R, Vesole D, Greipp P. A randomized 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. Blood 2006;108:799.

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.

U.S Food and Drug Administration FDA approves lenalidomide oral capsules (Revlimid) for use in combination with dexamethasone in patients with multiple myeloma. Available at Accessed 25 October 2012.

Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Gastineau DA et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment postperipheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia 2007;21:2035-42.

Mark T, Stern J, Furst JR, Jayabalan D, Zafer F, LaRow A et al. Stem cell mobilization with cyclophosphamide overcomes the suppressive effects of lenalidomide therapy on stem cell collection in multiple myeloma. Biol Blood Marrow Transplant 2008;14:795-8.

DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009;113:5720-6.

Giralt S, Stadtmauer EA, Harousseau JL, Palumbo A, Bensinger W, Comenzo RL, et al. International Myeloma Working Group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100). Leukemia 2009;23:1904-12.

Duarte RF, Shaw BE, Marin P, Kottaridis P, Ortiz M, Morante C et al. Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data. Bone Marrow Transplant 2011;46:52-8.

Micallef IN, Ho AD, Klein LM, Marulkar S, Gandhi PJ, McSweeney PA. Plerixafor (Mozobil) for stem cell mobilization in patients with multiple myeloma previously treated with lenalidomide. Bone Marrow Transplant 2011;46:350-5.

Brave M, Farrell A, Ching Lin S, et al. FDA review summary: Mozobil in combination with granulocyte colony-stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation. Oncology 2010;78(3-4):282-8.

Palumbo A, Rajkumar SV. Treatment of newly diagnosed myeloma. Leukemia 2009;23:449-56.

Harousseau JL, Attal M, Leleu X, Troncy J, Pegourie B, Stoppa AM et al. Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma. Haematologica 2006;91:1498-505.

Rosiñol L, Oriol A, Mateos MV, Sureda A, García-Sánchez P, Gutiérrez N et al. A phase II trial of alternating bortezomib and dexamethasone as induction regimen before autologous stem cell transplantation in younger patients with multiple myeloma: efficacy and clinical implications of tumour response kinetics. J Clin Oncol 2007;25:4452-8.

Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T et al. Assessment of proteasome inhibition for extending remissions (APEX) investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005;352:2487-98.

Richardson PG, Chanan-Khan A, Schlossman RL et al. Phase II trial of single agent bortezomib (Velcade®) in patients with previously untreated multiple myeloma (MM). Blood 2004;104:100a (A336).

Jagannath S, Durie BG, Wolf J, Camacho E, Irwin D, Lutzky J et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 2005;129:776-83.

San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M et al. VISTA Trial Investigators. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008;359:906-17.

Mateos MV, Hernández JM, Hernández MT, Gutiérrez NC, Palomera L, Fuertes M et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: Updated time-to-events results and prognostic factors for time to progression. Haematologic 2008;93:560-5.

Rosinol L, Cibeira MT, Martinez J, Mateos MV, Oriol A, Terol MJ et al. Thalidomide/dexamethasone (TD) vs bortezomib (velcade)/thalidomide/dexamethasone vs VBMCP/ VBAD/velcade as induction regimens in prior autologous stem cell transplantation (SCT) in multiple myeloma (MM): Results of a phase III PETHEMA/GEM trial. Blood 2009;114:59.

Palumbo A, Bringhen S, Rossi D, Ria R, Offidani M, Patriarca F et al. Bortezomib, melphalan, prednisolone and thalidomide (VMPT) followed by maintenance with bortezomib and thalidomide for initial treatment of elderly multiple myeloma patients. Blood 2009;114:58.

Harousseau J-L, Marit G, Caillot D et al. Velcade/dexamethasone (Vel/Dex) versus VAD as induction treatment prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM): an interim analysis of the IFM 2005-01 randomized Multicenterphase III Trial. Blood 2006;108:56.

Chanan-Khan A, Sonneveld P, Schuster MW, Stadtmauer EA, Facon T, Harousseau JL et al. Analysis of herpes zoster events among bortezomib-treated patients in the phase III APEX study. J Clin Oncol 2008;26:4784-90.

Durie BG. Treatment of myeloma-are we making progress? N Engl J Med 2008;359:964-6.

Anderson KC, Alsina M, Bensinger W, et al. NCCN clinical practice guidelines in oncology: multiple myeloma. J Natl Compr Canc Netw 2009;7:908-42.

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 Français du Myélome. N Engl J Med 1996;335:91-7.

Fermand JP, Katsahian S, Divine M, Leblond V, Dreyfus F, Macro M et al. Highdose 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;23:9227-33.

Blade J, Sureda A, Ribera JM, Mediavilla JD, Larafia JG, Palomera L et al. High dose therapy/auto transplantation/intensification versus continued conventional chemotherapy in multiple myeloma patients responding to initial chemotherapy: Definitive results from PETHEMA after a median follow up of 66 months. Blood 2003;102:42a.

Fermand JP, Ravaud P, Chevret S, Divine M, Leblond V, Belanger C et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: upfront or rescue treatment? results of a multicenter sequential randomized clinical trial. Blood 1998;92:3131-6.

Barlogie B, Kyle R, Anderson K, et al. Comparable survival in multiple myeloma (MM) with high dose therapy (HDT) employing MEL 140 mg/m2 + TBI 12 Gy autotransplants versus standard dose therapy with VBMCP and no benefit from interferon (IFN) maintenance: results of Intergroup Trial S9321[abstract]. Blood 2003;102:42a.

Rajkumar SV, Fonseca R, Lacy MQ, et al. Autologous stem cell transplantation for relapsed and primary refractory myeloma. Bone Marrow Transplant 1999;23:1267-72.

Blade J, Esteve J. Treatment approaches for relapsing and refractory multiple myeloma. Acta Oncol 2000;39:843-7.

Blade J, Vesole DH, Gertz M. High-dose therapy in multiple myeloma. Blood 2003;102:3469-70.

Barlogie B, Jagannath S, Vesole DH, Naucke S, Cheson B, Mattox S et al. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood 1997;89:789-93.

Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003;349:2495-502.

Mehta J, Singhal S. Graft-versus-myeloma. Bone Marrow Transplant 1998;22:835-43.

Gahrton G, Svensson H, Cavo M, et al, European Group for Blood and Marrow Transplantation. Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983-93 and 1994-8 at European Group for Blood and Marrow Transplantation centres. Br J Haematol 2001;113:209-16.

Kumar A, Kharfan-Dabaja MA, Glasmacher A, Djulbegovic B. Tandem versus single autologous hematopoietic cell transplantation for the treatment of multiple myeloma: A systematic review and meta-analysis. J Natl Cancer Inst 2009;101:100-6.

Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 2007;356:1110-20.

Garban F, Attal M, Michallet M, Hulin C, Bourhis JH, Yakoub-Agha I et al. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) in high-risk de novo multiple myeloma. Blood 2006;107:3474-80.

Rosiñol L, Pérez-Simón JA, Sureda A, de la Rubia J, de Arriba F, Lahuerta JJ et al. A prospective PETHEMA study of tandem autologous transplantatin versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma. Blood 2008;112:3591-3.

Crawley C, Iacobelli S, Björkstrand B, Apperley JF, Niederwieser D, Gahrton G. Reduced-intensity conditioning for myeloma: Lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning. Blood 2007;109:3588-94.

Rotta M, Storer BE, Sahebi F, Shizuru JA, Bruno B, Lange T et al. Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting. Blood 2009;113:3383-91.

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;27:3664-70.

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: Randomized controlled trial. Lancet 2006;367:825-31.

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;112:3107-14.

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;370:1209-18.

Bennet CL, Angelotta C, Yarnold PR, Evens AM, Zonder A, Raisch DW, et al. Thalidomide and lenalidomide-associated thromboembolism among patients with cancer. JAMA 2006;296:2559-60.

Ludwig H, Hajek R, Tothova E, Drach J, Adam Z, Labaret B, et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood 2009;113:3435-42.

Palumbo A, Falco P, Falcone A, Corradini P, Di Raimondo F, Giuliani N et al. Oral revlimid plus melphalan and prednisone (R-MP) for newly diagnosed multiple myeloma: a phase I-II study. J Clin Oncol 2007;25:4459-65.

Richardson P, Jagannath S, Raje N, Jakubowiak A, Lonial S, Ghobrial I et al. Lenalidomide, bortezomib and dexamethasone (Rev/Vel/Dex) as front line therapy for patients with multiple myeloma (MM). Blood 2007;110:2714.

Badros AZ. The role of maintenance therapy in the treatment of multiple myeloma. J Natl Compr Canc Netw 2010;8:21-7.

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.

Berenson JR, Crowley JJ, Grogan TM, Zangmeister J, Briggs AD, Mills GM et al.Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood 2002;99:3163-8.

Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006;354:1021-30.

Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 2006;108:3289-94.

Spencer A, Prince HM, Roberts AW, Prosser IW, Bradstock KF, Coyle L, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol 2009;27:1788-93.

Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, et al. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol 2010;28:800-7.

McCarthy P, Owzar K, Anderson K, Hofmeister CC, Hurd DD, Hassoun H, et al. Phase III intergroup study of lenalidomide versus placebo maintenance therapy following single autologous hematopoietic stem cell transplantation (AHSCT) for multiple myeloma: CALGB 100104. Blood 2010;116:21-2.

Attal M, Lauwers cances V, Marit G, Caillot D, Facon T, Hulin C et al. Maintenance treatment with lenalidomide after transplantation for MYELOMA: final analysis of the IFM 2005-02. Blood 2010;116:141. Abstract 310.

Palumbo A, Delforge M, Catalano J, Hajek R, Kropff M, Petrucci MT et al. A Phase 3 Study evaluating the efficacy and safety of lenalidomide combined with melphalan and prednisone in patients >65 years with newly diagnosed multiple myeloma (NDMM): continuous use of lenalidomide vs fixed-duration regimens. Blood 2010;116:273-4.

Schillera GJ, Liaoa M, Sohna JP, Malonea R, Bartonia K, Habtemariam B et al. Phase I/II trial of bortezomib maintenance following autologous peripheral blood progenitor cell transplantation as treatment for intermediate- and advanced-stage multiple myeloma. Biol Blood Marrow Transplant 2008;13:57. doi:10.1016/j.bbmt.2006.12.157.

Kastritis E, Palumbo A, Dimopoulos MA. Treatment of relapsed/refractory multiple myeloma. Semin Hematol 2009;46:143-57.

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;341:1565-71.

Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA et al.Long-term follow-up on overall survival from the MM-009 and MM-010 phase II trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia 2009;23:2147-52.

Mehta J, Tricot G, Jagannath S, Ayers D, Singhal S, Siegel D et al. Salvage autologous or allogeneic transplantation for multiple myeloma refractory to or relapsing after a first-line autograft? Bone Marrow Transplant 1998;21:887-92.

Elice F, Raimondi R, Tosetto A, D'Emilio A, Di Bona E, Piccin A et al. Prolonged overall survival with second on-demand autologous transplant in multiple myeloma. Am J Hematol 2006;81:426-31.

Olin RL, Vogl DT, Porter DL, Luger SM, Schuster SJ, Tsai DE, et al. Second auto-SCT is safe and effective salvage therapy for relapsed multiple myeloma. Bone Marrow Transplant 2009;43:417-22.

de Lavallade H, El-Cheikh J, Faucher C, Fürst S, Stoppa AM, Coso D et al. Reduced-intensity conditioning allogeneic SCT as salvage treatment for relapsed multiple myeloma. Bone Marrow Transplant 2008;41:953-60.

Orlowski RZ, Nagler A, Sonneveld P, Bladé J, Hajek R, Spencer A et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma. Combination therapy improves time to progression. J Clin Oncol 2007;25:3892-901.

Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 2007;357:2133-42.

Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 2007;357:2123-32.

Richardson PG, Sonneveld P, Schuster M, Irwin D, Stadtmauer E, Facon T et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood 2007;110:3557-60.

Moehler TM, Neben K, Benner A ,Egerer G, Krasniqi F, Ho AD et al. Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy. Blood 2001;98:3846-8.

Baz R, Walker E, Karam MA, Choueiri TK, Jawde RA, Bruening K et al. Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy. Ann Oncol 2006;17:1766-71.

Morgan GJ, Schey SA, Wu P, Srikanth M, Phekoo KJ, Jenner M et al. Lenalidomide (Revlimid), in combination with cyclophosphamide and dexamethasone (RCD), is an effective and tolerated regimen for myeloma patients. Br J Haematol 2007;137:268-9.

Richardson P, Siegel D, Baz R, et al. A phase 1/2 multi-center, randomized, open label dose escalation study to determine the maximum tolerated dose, safety, and efficacy of pomalidomide alone or in combination with low-dose dexamethasone in patients with relapsed and refractory multiple myeloma who have received prior treatment that includes lenalidomide and bortezomib. Blood 2010;116:377-8.

Lacy MQ, Allred JB, Gertz MA, Hayman SR, Short KD, Buadi F et al Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood 2011;118:2970-5.

Schey SA, Fields P, Bartlett JB, Clarke IA, Ashan G, Knight RD et al. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol 2004;22:3269-76.

Lacy MQ, Hayman SR, Gertz MA Short KD, Dispenzieri A, Kumar S, et al. Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia 2010;24:1934-9.

Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood 2007;110:3281-90.

Parlati F, Lee SJ, Aujay M, Suzuki E, Levitsky K, Lorens JB et al. Carfilzomib can induce tumor cell death through selective inhibition of the chymotrypsin-like activity of the proteasome. Blood 2009;114:3439-47.

Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood 2012;120:2817-25.

Kyle RA, Yee GC, Somerfield MR, Flynn PJ, Halabi S, Jagannath S 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.

Gucalp R, Theriault R, Gill I, Madajewicz S, Chapman R, Navari R, et al. Treatment of cancer-associated hypercalcemia: double-blind comparison of rapid and slow intravenous infusion regimens of pamidronate disodium and saline alone. Arch Intern Med 1994;154:1935-44.

Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001;19:558-67.

Fourney DR, Schomer DF, Nader R, Chlan-Fourney J, Suki D, Ahrar K, et al. Percutaneous vertebroplastyand kyphoplasty for painful vertebral body fractures in cancer patients. J Neurosurg 2003;98(1, suppl):21-30.

Ludwig H. Prevalence, pathogenesis and treatment of anemia with erythropoietic agents in multiple myeloma. Hematol J 2005;90:10-11.

Garton JP, Gertz MA, Witzig TE, , Greipp PR, Lust JA, Schroeder G et al. Epoetin alfa for the treatment of the anemia of multiple myeloma: a prospective, randomized, placebo-controlled, double-blind trial. Arch Intern Med 1995;155:2069-74.

Dammacco F, Castoldi G, Rodjer S. Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma. Br J Haematol 2001;113:172-9.

Oken MM, Pomeroy C, Weisdorf D, Bennett JM. Prophylactic antibiotics for the prevention of early infection in multiple myeloma. Am J Med 1996;100:624-8.

Chapel HM, Lee M. The use of intravenous immune globulin in multiple myeloma. Clin Exp Immunol 1994;97:21-4.

Yussim E, Schwartz E, Sidi Y, Ehrenfeld M. Acute renal failure precipitated by non-steroidal anti-inflammatory drugs (NSAIDs) in multiple myeloma. Am J Hematol 1998;58:142-4.

Wu MJ, Kumar KS, Kulkarni G, Kaiser H. Multiple myeloma in naproxen-induced acute renal failure. N Engl J Med 1987;317:170-1.

Johnson WJ, Kyle RA, Pineda AA, O’Brien PC, Holley KE. Treatment of renal failure associated with multiple myeloma: plasmapheresis, hemodialysis, and chemotherapy. Arch Intern Med 1990;150:863-9.

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;22:414-23.

Gertz MA, Kyle RA. Hyperviscosity syndrome. J Intensive Care Med 1995;10:128-41.

Ocio EM, Mateos MV, Maiso P, Pandiella A, San Miguel JF. New drugs in multiple myeloma: mechanisms of action and phase I/II clinical findings. Lancet Oncol 2008;9:1157-65.

Podar K, Chauban D, Anderson KC. Bone marrow microenvironment and the identification of new targets for myeloma therapy. Leukemia 2009;23:10-24.

U.S Food and Drug Administration. Carfilzomib. Available at Accessed 23 October 2012.

Celgene Submits Pomalidomide for FDA Approval, The Myeloma Beacon Staff. Available at Accessed 23 October 2012.

Ocio EM, Vilanova D, Atadja P, Maiso P, Crusoe E, Fernández-Lázaro D et al. In vitro and in vivo rationale for the triple combination of panobinostat (LBH 589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma. Haematologica 2010;95:794-803.

Li V. Panobinostat Combination May Be Effective In Relapsed And Velcade-Refractory Multiple Myeloma (ASH 2011). Available at Accessed 23 October 2012.

Martin SK, Diamond P, Williams SA, To LB, Peet DJ, Fujii N et al. Hypoxia-inducible factor-2 is a novel regulator of aberrant CXCL12 expression in multiple myeloma plasma cells. Haematologica 2010;95:776-84.

Wischnewski F, Pantel K, Schwarzenbach H. Promoter demethylation and histone acetylation mediate gene expression of MAGE-A1, -A2, -A3, and -A12 in human cancer cells. Mol Cancer Res 2006;4:339-49.

Andrade VC, Vettore AL, Felix RS, Almeida MS, Carvalho F, Oliveira JS et al. Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients. Cancer Immun 2008;8:2.

Atanackovic D, Hildebrandt Y, Jadczak A, Cao Y, Luetkens T, Meyer S et al. Cancer-testis antigens MAGE-C1/CT7 and MAGE-A3 promote the survival of multiple myeloma cells. Haematologica 2010;95:785-93.

de Carvalho F, Vettore AL, Colleoni GW. Cancer/Testis Antigen MAGE-C1/CT7: New Target for Multiple Myeloma Therapy. Clin Dev Immunol 2012;2012:257695. doi:10.1155/2012/257695.

A Safety and Efficacy Study of CNTO 328 in Patients with B-Cell Non-Hodgkin's Lymphoma, Multiple Myeloma, or Castleman's Disease, clinical Available at Accessed 23 October 2012.

Anderson KC. New therapies. The comprehensive guide to Baniff: Understanding the VIIIth international myeloma workshop, Published by International Myeloma Foundation, USA. Available at Accessed 23 October 2012.

Qu X, Du J, Zhang C, Fu W, Xi H, Zou J, Hou J. Arsenic Trioxide Exerts Antimyeloma Effects by Inhibiting Activity in the Cytoplasmic Substrates of Histone Deacetylase 6. PLoS One 2012;7(2):e32215.doi:10.1371/journal.pone.0032215.




How to Cite

Gupta, M., Pal, R. A. G. K., & Tikoo, D. (2017). Multiple myeloma: the disease and its treatment. International Journal of Basic & Clinical Pharmacology, 2(2), 103–121. Retrieved from



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