Multiple Myeloma 

  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: May 8, 2012
 

Background

Multiple myeloma (MM) (see images below) is a debilitating malignancy that is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. First described in 1848, MM is characterized by a proliferation of malignant plasma cells and a subsequent overabundance of monoclonal paraprotein (M protein). An intriguing feature of MM is that the antibody-forming cells (ie, plasma cells) are malignant and, therefore, may cause unusual manifestations.

The proliferation of plasma cells in MM may interfere with the normal production of blood cells, resulting in leukopenia, anemia, and thrombocytopenia. The cells may cause soft-tissue masses (plasmacytomas) or lytic lesions in the skeleton. Feared complications of MM are bone pain, hypercalcemia, renal failure, and spinal cord compression.

The aberrant antibodies that are produced lead to impaired humoral immunity, and patients have a high prevalence of infection, especially with encapsulated organisms such as Pneumococcus. The overproduction of these antibodies may lead to hyperviscosity, amyloidosis, and renal failure. (See Pathophysiology.)

The American Cancer Society estimated that about 20,580 new cases of MM (11,680 in men and 8,900 in women) would be diagnosed during 2009. In the United States, the lifetime risk of getting MM is 1 in 161 (0.62%).[1] About 10,580 Americans (5,640 men and 4,940 women) are expected to have died of MM in 2008.[1] (See Epidemiology.)

The 5-year relative survival rate for MM is around 35%. Survival is higher in younger people and lower in the elderly.[1, 2, 3] (See Prognosis.)

The presentation of MM can range from asymptomatic to severely symptomatic with complications requiring emergent treatment. Systemic ailments include bleeding, infection and renal failure; local catastrophes include pathologic fractures and spinal cord compression. (See Clinical Presentation.)

Although patients benefit from treatment (ie, longer life, less pain, fewer complications), currently no cure exists. Recent advances in therapy have helped to lessen the occurrence and severity of adverse effects of MM. (See Treatment and Management.)

Also see the topic Imaging Multiple Myeloma.

Next

Pathophysiology

MM is characterized by neoplastic proliferation of plasma cells involving more than 10% of the bone marrow (see the images below). Increasing evidence suggests that the bone marrow microenvironment of tumor cells plays a pivotal role in the pathogenesis of myelomas.[4] This information has resulted in the expansion of treatment options.

Bone marrow aspirate demonstrating plasma cells ofBone marrow aspirate demonstrating plasma cells of multiple myeloma. Note the blue cytoplasm, eccentric nucleus, and perinuclear pale zone (or halo). All images and text are (c) 2002 by the American Society of Hematology. All rights reserved. Bone marrow biopsy demonstrating sheets of malignaBone marrow biopsy demonstrating sheets of malignant plasma cells in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.

The malignant cells of MM, plasma cells, and plasmacytoid lymphocytes are the most mature cells of B-lymphocytes. B-cell maturation is associated with a programmed rearrangement of DNA sequences in the process of encoding the structure of mature immunoglobulins. It is characterized by overproduction of monoclonal immunoglobulin G (IgG), immunoglobulin A (IgA), and/or light chains, which may be identified with serum protein electrophoresis (SPEP) or urine protein electrophoresis (UPEP).

The role of cytokines in the pathogenesis of MM is an important area of research. Interleukin (IL)–6 is also an important factor promoting the in vitro growth of myeloma cells. Other cytokines are tumor necrosis factor and IL-1b.

The pathophysiologic basis for the clinical sequelae of MM involves the skeletal, hematologic, renal, and nervous systems, as well as general processes (see below).

Skeletal processes

Plasma-cell proliferation causes extensive skeletal destruction with osteolytic lesions, anemia, and hypercalcemia. Mechanisms for hypercalcemia include bony involvement and, possibly, humoral mechanisms. Isolated plasmacytomas (which affect 2-10% of patients) lead to hypercalcemia through production of the osteoclast-activating factor.

Destruction of bone and its replacement by tumor may lead to pain, spinal cord compression, and pathologic fracture. The mechanism of spinal cord compression symptoms may be the development of an epidural mass with compression, a compression fracture of a vertebral body destroyed by multiple myeloma, or, rarely, an extradural mass. With pathologic fracture, bony involvement is typically lytic in nature.

Hematologic processes

Bone marrow infiltration by plasma cells results in neutropenia, anemia, and thrombocytopenia. In terms of bleeding, M components may interact specifically with clotting factors, leading to defective aggregation.

Renal processes

The most common mechanisms of renal injury in MM are direct tubular injury, amyloidosis, or involvement by plasmacytoma.[5, 6] Renal conditions that may be observed include hypercalcemic nephropathy, hyperuricemia due to renal infiltration of plasma cells resulting in myeloma, light-chain nephropathy, amyloidosis, and glomerulosclerosis.

Neurologic processes

The nervous system may be involved as a result of radiculopathy and/or cord compression due to nerve compression and skeletal destruction (amyloid infiltration of nerves).

General processes

General pathophysiologic processes include hyperviscosity syndrome. This syndrome is infrequent in MM and occurs with IgG1, IgG3, or IgA. MM may involve sludging in the capillaries, which results in purpura, retinal hemorrhage, papilledema, coronary ischemia, or central nervous system (CNS) symptoms (eg, confusion, vertigo, seizure). Cryoglobulinemia causes Raynaud phenomenon, thrombosis, and gangrene in the extremities.

Previous
Next

Etiology

The precise etiology of MM has not yet been established. Roles have been suggested for a variety of factors, including genetic causes, environmental or occupational causes, MGUS, radiation, chronic inflammation, and infection.

Genetic causes

MM has been reported in 2 or more first-degree relatives and in identical twins, although no evidence suggests a hereditary basis for the disease. A study by the Mayo clinic found MM in 8 siblings from a group of 440 patients; these 8 siblings had different heavy chains but the same light chains.

Some studies have shown that abnormalities of certain oncogenes, such as c-myc, are associated with development early in the course of plasma cell tumors and that abnormalities of oncogenes such as N-ras and K-ras are associated with development after bone marrow relapse. Abnormalities of tumor suppressor genes, such as TP53, have been shown to be associated with spread to other organs.[1]

Ongoing research is investigating whether human leukocyte antigen (HLA)-Cw5 or HLA-Cw2 may play a role in the pathogenesis of multiple myeloma.

Environmental or occupational causes

Case-controlled studies have suggested a significant risk of developing MM in individuals with significant exposures in the agriculture, food, and petrochemical industries. An increased risk has been reported in farmers, especially in those who use herbicides and insecticides, and in people exposed to benzene and other organic solvents. Long-term (>20 y) exposure to hair dyes has been tied to an excessive risk of developing MM.

MGUS

Approximately 19% of patients with MGUS develop MM within 2-19 years.

A study by Wadhera et al examined secondary MGUS that developed in patients with MM. Of 1942 patients with MM, 128 (6.6%) developed a secondary MGUS at a median of 12 months from the diagnosis of MM. Overall survival was superior in patients with MM who developed secondary MGUS compared with the rest of the cohort.[7]

Radiation

Radiation may play a role in some patients. An increased risk has been reported in atomic-bomb survivors exposed to more than 50 Gy: In 109,000 survivors of the atomic bombing of Nagasaki during World War II, 29 died from multiple myeloma between 1950 and 1976. Some more recent studies, however, do not confirm that these survivors have an increased risk of developing multiple myeloma.

A recent study of workers at the Oak Ridge Diffusion Plant in eastern Tennessee showed only a weak correlation of risk of multiple myeloma to uranium exposure.[8]

Chronic inflammation

A relationship between MM and preexisting chronic inflammatory diseases has been suggested. However, a case-control study provides no support for the role of chronic antigenic stimulation.

Infection

Human herpesvirus 8 (HPV8) infection of bone marrow dendritic cells was found in patients with MM and in some patients with MGUS.

Previous
Next

Epidemiology

MM accounts for 10% of all hematologic cancers.[9, 10] The age-adjusted annual incidence of MM is 4.3 cases per 100,000 white men, 3 cases per 100,000 white women, 9.6 cases per 100,000 black men, and 6.7 cases per 100,000 black women.

The American Cancer Society estimated that in the United States, 20,580 new cases of MM would be diagnosed during 2009, with 11,680 cases occurring in men and 8,900 in women. The lifetime risk of getting MM is 1 in 161 (0.62%).[1]

The median age of patients with MM is 68 years for men and 70 years for women. Only 18% of patients are younger than 50 years, and 3% of patients are younger than 40 years. The male-to-female ratio of multiple myeloma is approximately 3:2.

In the United States, African Americans are twice as likely as whites to have myeloma, with a ratio of 2:1. Myeloma is rare among people of Asian descent, with an incidence of only 1-2 cases per 100,000 population.

According to a study of the ethnic disparities among patients with MM, Hispanics had the youngest median age at diagnosis (65 years) and Whites had the oldest (71 years). Asians had the best overall survival rates, while Hispanics had the worst.[11]

Previous
Next

Prognosis

MM is a heterogeneous disease, with survival ranging from 1 year to more than 10 years. Median survival in unselected patients with MM is 3 years. The 5-year relative survival rate is around 35%. Survival is higher in younger people and lower in the elderly.[1] It was estimated that about 10,580 Americans (5,640 men and 4,940 women) would die of multiple myeloma in 2008.[1]

The tumor burden and the proliferation rate are the 2 key indicators for the prognosis in patients with MM. Many schemas have been published to aid in determining the prognosis. One schema uses C-reactive protein (CRP) and beta-2 microglobulin (which is an expression of tumor burden) to predict survival as follows[12] :

  • If levels of both proteins are less than 6 mg/L, the median survival is 54 months.
  • If the level of only one component is less than 6 mg/L, the median survival is 27 months.
  • If levels of both protein values are greater than 6 mg/L, the median survival is 6 months.

Poor prognostic factors include the following:

  • Tumor mass
  • Hypercalcemia
  • Bence Jones proteinemia
  • Renal impairment (ie, stage B disease or creatinine level >2 mg/dL at diagnosis)

The prognosis by treatment is as follows:

  • Conventional therapy: Overall survival is approximately 3 years, and event-free survival is less than 2 years.
  • High-dose chemotherapy with stem-cell transplantation: The overall survival rate is greater than 50% at 5 years.
  • Serum amyloid P retention: More than 50% of patients have a median survival of approximately 11 months.
  • Serum amyloid P retention: Median survival is 24 months.

Bacterial infection is the leading cause of death in patients with myeloma.[1]

A study by Larsen et al found that a significant reduction in plasma cell proliferation in patients with newly diagnosed MM is an important predictor of survival.[13]

Previous
Next

Patient Education

Patient education is very important in the management of MM. The International Myeloma Foundation (IMF) offers educational resources, a quarterly newsletter, and conferences. Patients or physicians can contact the IMF by phone at (800) 452-CURE (800-452-2873) in the United States and Canada or on the Web at International Myeloma Foundation.

Patient education should address, at a minimum, the following questions:

  • What is MM, and how does it affect the body?
  • What are the causes of MM?
  • What is the treatment for MM?
  • What are the adverse effects of medicine? (As an example, patients should be informed of the risk of osteonecrosis of the jaw, which has been associated with bisphosphonate therapy in MM.)
  • What are some of the complications of MM?
  • Where can additional information be found?

For patient education information, see Blood and Lymphatic System Center, as well as Myeloma.

Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Karen Seiter, MD  Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching; Novartis Consulting fee Speaking and teaching; Eisai Honoraria Speaking and teaching; Celgene Honoraria Speaking and teaching

Coauthor(s)

Dhaval Shah, MD  Fellow, Department of Hematology/Oncology, Baylor College of Medicine

Disclosure: Nothing to disclose.

Sara J Grethlein, MD  Senior Attending Physician, Cancer Treatment Center, Bassett Healthcare Network

Sara J Grethlein, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

Seema S Rizvi, MD  Associate Medical Director, Lutheran Care Center

Seema S Rizvi, MD is a member of the following medical societies: American Academy of Family Physicians and American Medical Association

Disclosure: Nothing to disclose.

Lilian M Thomas, MD  Fellow, Department of Hematology/Oncology, State University of New York Upstate Medical University

Lilian M Thomas, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Koyamangalath Krishnan, MD, FRCP, FACP  Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Harris Gellman, MD  Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami, Leonard M Miller School of Medicine

Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

  1. Detailed Guide: Multiple Myeloma What Are the Key Statistics About Multiple Myeloma?. American Cancer Society. Available at http://bit.ly/dMwLDk. Accessed May 28, 2009.

  2. Rodon P. Management and treatment of multiple myeloma in elderly patients. Ann Long-Term Care. 2002;10:20-7.

  3. Ludwig H, Durie BG, Bolejack V, Turesson I, Kyle RA, Blade J, et al. Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10 549 patients from the International Myeloma Working Group. Blood. Apr 15 2008;111(8):4039-47. [Medline].

  4. Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. Multiple myeloma. Lancet. Jul 25 2009;374(9686):324-39. [Medline].

  5. Ludwig H, Drach J, Graf H, Lang A, Meran JG. Reversal of acute renal failure by bortezomib-based chemotherapy in patients with multiple myeloma. Haematologica. Oct 2007;92(10):1411-4. [Medline].

  6. Zucchelli P, Pasquali S, Cagnoli L, Ferrari G. Controlled plasma exchange trial in acute renal failure due to multiple myeloma. Kidney Int. Jun 1988;33(6):1175-80. [Medline].

  7. Wadhera RK, Kyle RA, Larson DR, et al. Incidence, clinical course, and prognosis of secondary monoclonal gammopathy of undetermined significance in patients with multiple myeloma. Blood. Sep 15 2011;118(11):2985-7. [Medline].

  8. Yiin JH, Anderson JL, Daniels RD, Seel EA, Fleming DA, Waters KM, et al. A nested case-control study of multiple myeloma risk and uranium exposure among workers at the Oak Ridge Gaseous Diffusion Plant. Radiat Res. Jun 2009;171(6):637-45. [Medline].

  9. 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. Nov 2008;81(5):329-43. [Medline].

  10. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. Jan 2009;23(1):3-9. [Medline]. [Full Text].

  11. Ailawadhi S, Aldoss IT, Yang D, Razavi P, Cozen W, Sher T, et al. Outcome disparities in multiple myeloma: a SEER-based comparative analysis of ethnic subgroups. Br J Haematol. Apr 26 2012;[Medline].

  12. Bataille R, Boccadoro M, Klein B, Durie B, Pileri A. C-reactive protein and beta-2 microglobulin produce a simple and powerful myeloma staging system. Blood. Aug 1 1992;80(3):733-7. [Medline].

  13. Larsen JT, Chee CE, Lust JA, Greipp PR, Rajkumar SV. Reduction in plasma cell proliferation after initial therapy in newly diagnosed multiple myeloma measures treatment response and predicts improved survival. Blood. Sep 8 2011;118(10):2702-7. [Medline].

  14. Bladé J, Fernández-Llama P, Bosch F, Montolíu J, Lens XM, Montoto S, et al. Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution. Arch Intern Med. Sep 28 1998;158(17):1889-93. [Medline].

  15. Dimopoulos M, Kyle R, Fermand JP, et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. May 5 2011;117(18):4701-5. [Medline].

  16. [Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology, Multiple Myeloma Version 1. 2011;Available with free registration at www.nccn.org. Accessed May 1 2011.

  17. Dimopoulos M, Terpos E, Comenzo RL, Tosi P, Beksac M, Sezer O, et al. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma. Leukemia. Sep 2009;23(9):1545-56. [Medline].

  18. Hung GU, Tsai CC, Tsai SC, Lin WY. Comparison of Tc-99m sestamibi and F-18 FDG-PET in the assessment of multiple myeloma. Anticancer Res. Nov-Dec 2005;25(6C):4737-41. [Medline].

  19. Shortt CP, Gleeson TG, Breen KA, McHugh J, O'Connell MJ, O'Gorman PJ, et al. Whole-Body MRI versus PET in assessment of multiple myeloma disease activity. AJR Am J Roentgenol. Apr 2009;192(4):980-6. [Medline].

  20. 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. Dec 1 2011;118(23):5989-95. [Medline].

  21. 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. Sep 1975;36(3):842-54. [Medline].

  22. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al. International staging system for multiple myeloma. J Clin Oncol. May 20 2005;23(15):3412-20. [Medline].

  23. Dimopoulos MA, Moulopoulos A, Smith T, Delasalle KB, Alexanian R. Risk of disease progression in asymptomatic multiple myeloma. Am J Med. Jan 1993;94(1):57-61. [Medline].

  24. He Y, Wheatley K, Clark O, Glasmacher A, Ross H, Djulbegovic B. Early versus deferred treatment for early stage multiple myeloma. Cochrane Database Syst Rev. 2003;CD004023. [Medline].

  25. Munshi NC, Anderson KC, Bergsagel PL, et al. Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood. May 5 2011;117(18):4696-700. [Medline].

  26. Klein U, Jauch A, Hielscher T, et al. Chromosomal aberrations +1q21 and del(17p13) predict survival in patients with recurrent multiple myeloma treated with lenalidomide and dexamethasone. Cancer. May 15 2011;117(10):2136-44. [Medline].

  27. Neben K, Lokhorst HM, Jauch A, et al. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. Jan 26 2012;119(4):940-8. [Medline].

  28. 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. Dec 2008;9(12):1157-65. [Medline].

  29. Palumbo A, Rajkumar SV. Treatment of newly diagnosed myeloma. Leukemia. Mar 2009;23(3):449-56. [Medline].

  30. Bensinger WI. Role of autologous and allogeneic stem cell transplantation in myeloma. Leukemia. Mar 2009;23(3):442-8. [Medline]. [Full Text].

  31. Jakubowiak AJ, Griffith KA, Reece DE, et al. Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial. Blood. Jul 21 2011;118(3):535-43. [Medline].

  32. Palumbo A, Cavo M, Bringhen S, et al. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. Mar 10 2011;29(8):986-93. [Medline].

  33. Zonder JA, Crowley J, Hussein MA, Bolejack V, Moore DF Sr, 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. Dec 23 2010;116(26):5838-41. [Medline]. [Full Text].

  34. Alexanian R, Dimopoulos M. The treatment of multiple myeloma. N Engl J Med. Feb 17 1994;330(7):484-9. [Medline].

  35. Anderson KC, Hamblin TJ, Traynor A. Management of multiple myeloma today. Semin Hematol. Jan 1999;36(1 Suppl 3):3-8. [Medline].

  36. Barlogie B, Shaughnessy J, Tricot G, Jacobson J, Zangari M, Anaissie E, et al. Treatment of multiple myeloma. Blood. Jan 1 2004;103(1):20-32. [Medline].

  37. Desikan KR, Dhodapkar MV, Munshi NC, Barlogie B. Recent advances in the treatment of multiple myeloma. Curr Opin Hematol. Jul 1999;6(4):216-21. [Medline].

  38. Kanis JA, McCloskey EV. Bisphosphonates in multiple myeloma. Cancer. Jun 15 2000;88(12 Suppl):3022-32. [Medline].

  39. Singhal S, Mehta J, Barlogie B. Advances in the treatment of multiple myeloma. Curr Opin Hematol. Jul 1997;4(4):291-7. [Medline].

  40. Lust JA, Lacy MQ, Zeldenrust SR, Dispenzieri A, Gertz MA, Witzig TE, et al. Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1{beta}-induced interleukin 6 production and the myeloma proliferative component. Mayo Clin Proc. Feb 2009;84(2):114-22. [Medline]. [Full Text].

  41. Zonder JA, Crowley J, Hussein MA, et al. Superiority of lenalidomide (Len) plus high-dose dexamethasone (HD) compared to HD alone as treatment of newly-diagnosed multiple myeloma (NDMM): results of the randomized, double-blinded, placebo-controlled SWOG trial S0232 [abstract 77]. Blood. 2007;110:32a. [Full Text].

  42. Lokhorst HM, Sonneveld P, Cornelissen JJ, Joosten P, van Marwijk Kooy M, Meinema J, et al. Induction therapy with vincristine, adriamycin, dexamethasone (VAD) and intermediate-dose melphalan (IDM) followed by autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma. Bone Marrow Transplant. Feb 1999;23(4):317-22. [Medline].

  43. Zervas K, Mihou D, Katodritou E, Pouli A, Mitsouli CH, Anagnostopoulos A, et al. VAD-doxil versus VAD-doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek Myeloma Study Group. Ann Oncol. Aug 2007;18(8):1369-75. [Medline].

  44. Rajkumar SV, Jacobus S, Callander N, et al. A randomized trial of lenalidomide plus high-dose dexamethasone (RD) versus lenalidomide plus low-dose dexamethasone (Rd) in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group [abstract 74]. Blood. 2007;11(1):110:31a. [Full Text].

  45. [Best Evidence] 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. Jan 2010;11(1):29-37. [Medline].

  46. 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. Feb 1 2008;111(3):1101-9. [Medline].

  47. 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. Jun 26 2003;348(26):2609-17. [Medline].

  48. Harousseau JL, Mathiot C, Attal M, et al. VELCADE/dexamethasone (Vel/D) versus VAD as induction treatment prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM): updated results of the IFM 2005/01 trial [abstract 450]. Blood. 2007;110:139a. [Full Text].

  49. Cavo M, Patriarca F, Tacchetti P, et al. . Bortezomib (Velcade[R])-thalidomide-dexamethasone (VTD) vs thalidomide-dexamethasone (TD) in preparation for autologous stem-cell (SC) transplantation (ASCT) in newly diagnosed multiple myeloma (MM) [abstract 73]. Blood. 2007;110:30a. [Full Text].

  50. [Best Evidence] 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. May 1 2010;28(13):2259-66. [Medline].

  51. 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. Nov 11 2010;116(19):3743-50. [Medline].

  52. Sher T, Ailawadhi S, Miller KC, et al. A steroid-independent regimen of bortezomib, liposomal doxorubicin and thalidomide demonstrate high response rates in newly diagnosed multiple myeloma patients. Br J Haematol. Jul 2011;154(1):104-10. [Medline].

  53. Vickrey E, Allen S, Mehta J, Singhal S. Acyclovir to prevent reactivation of varicella zoster virus (herpes zoster) in multiple myeloma patients receiving bortezomib therapy. Cancer. Jan 1 2009;115(1):229-32. [Medline].

  54. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. May 2011;12(5):431-40. [Medline].

  55. Mateos MV, Gutierrez NC, Martin-Ramos ML, et al. Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance. Blood. Oct 27 2011;118(17):4547-53. [Medline].

  56. Jagannath S, Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, et al. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia. Jan 2007;21(1):151-7. [Medline].

  57. Sagaster V, Ludwig H, Kaufmann H, Odelga V, Zojer N, Ackermann J, et al. Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion. Leukemia. Jan 2007;21(1):164-8. [Medline].

  58. 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. Dec 1998;16(12):3832-42. [Medline].

  59. [Best Evidence] 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. Oct 6 2007;370(9594):1209-18. [Medline].

  60. Palumbo A, Falco P, Falcone A, Benevolo G, Canepa L, Gay F, et al. Melphalan, prednisone, and lenalidomide for newly diagnosed myeloma: kinetics of neutropenia and thrombocytopenia and time-to-event results. Clin Lymphoma Myeloma. Apr 2009;9(2):145-50. [Medline].

  61. [Best Evidence] 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. Aug 1 2009;27(22):3664-70. [Medline].

  62. 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. Sep 2 2010;116(9):1405-12. [Medline].

  63. 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. Aug 4 2011;118(5):1239-47. [Medline].

  64. Gay F, Larocca A, Wijermans P, et al. Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood. Mar 17 2011;117(11):3025-31. [Medline].

  65. 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. Aug 4 2011;118(5):1231-8. [Medline]. [Full Text].

  66. 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. Apr 9 2009;113(15):3435-42. [Medline].

  67. van Rhee F, Dhodapkar M, Shaughnessy JD Jr, Anaissie E, Siegel D, Hoering A, et al. First thalidomide clinical trial in multiple myeloma: a decade. Blood. Aug 15 2008;112(4):1035-8. [Medline]. [Full Text].

  68. Kumar S, Witzig TE, Rajkumar SV. Thalidomid: current role in the treatment of non-plasma cell malignancies. J Clin Oncol. Jun 15 2004;22(12):2477-88. [Medline].

  69. 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. Nov 22 2007;357(21):2133-42. [Medline].

  70. Lacy MQ, Allred JB, Gertz MA, 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. Sep 15 2011;118(11):2970-5. [Medline].

  71. Moreau P, Hullin C, Garban F, Yakoub-Agha I, Benboubker L, Attal M, et al. Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol. Blood. Jan 1 2006;107(1):397-403. [Medline].

  72. Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P, Patriarca F, et al. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol. Jun 10 2007;25(17):2434-41. [Medline].

  73. [Best Evidence] Barlogie B, Attal M, Crowley J, van Rhee F, Szymonifka J, Moreau P, et al. Long-term follow-up 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. Mar 1 2010;28(7):1209-14. [Medline]. [Full Text].

  74. 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. Jul 11 1996;335(2):91-7. [Medline].

  75. Gerull S, Goerner M, Benner A, Hegenbart U, Klein U, Schaefer H, et al. Long-term outcome of nonmyeloablative allogeneic transplantation in patients with high-risk multiple myeloma. Bone Marrow Transplant. Dec 2005;36(11):963-9. [Medline].

  76. Vesole DH, Zhang L, Flomenberg N, Greipp PR, Lazarus HM, Huff CA. A Phase II trial of autologous stem cell transplantation followed by mini-allogeneic stem cell transplantation for the treatment of multiple myeloma: an analysis of Eastern Cooperative Oncology Group ECOG E4A98 and E1A97. Biol Blood Marrow Transplant. Jan 2009;15(1):83-91. [Medline].

  77. Bruno B, Rotta M, Patriarca F, Mattei D, Allione B, Carnevale-Schianca F, et al. Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo. Blood. Apr 2 2009;113(14):3375-82. [Medline]. [Full Text].

  78. 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. Apr 2 2009;113(14):3383-91. [Medline]. [Full Text].

  79. Moreau P, Attal M, Pégourié B, et al. Achievement of VGPR to induction therapy is an important prognostic factor for longer PFS in the IFM 2005-01 trial. Blood. Mar 17 2011;117(11):3041-3044. [Medline].

  80. 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. Oct 20 2010;28(30):4621-9. [Medline].

  81. Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, 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. Dec 18 2010;376(9758):2075-85. [Medline].

  82. Cooper MR, Dear K, McIntyre OR, Ozer H, Ellerton J, Canellos G, et al. A randomized clinical trial comparing melphalan/prednisone with or without interferon alfa-2b in newly diagnosed patients with multiple myeloma: a Cancer and Leukemia Group B study. J Clin Oncol. Jan 1993;11(1):155-60. [Medline].

  83. Morgan GJ, Child JA, Gregory WM, et al. Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial. Lancet Oncol. Aug 2011;12(8):743-52. [Medline].

  84. Berenson JR, Lichtenstein A, Porter L, Dimopoulos MA, Bordoni R, George S, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med. Feb 22 1996;334(8):488-93. [Medline].

  85. 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. Jun 10 2007;25(17):2464-72. [Medline].

  86. Wang EP, Kaban LB, Strewler GJ, Raje N, Troulis MJ. Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy. J Oral Maxillofac Surg. Jul 2007;65(7):1328-31. [Medline].

  87. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. National Guideline Clearinghouse. Available at http://guideline.gov/summary/summary.aspx?doc_id=10857. Accessed May 1, 2009.

  88. Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. Dec 11 2010;376(9757):1989-99. [Medline].

  89. Djulbegovic B, Wheatley K, Ross J, Clark O, Bos G, Goldschmidt H, et al. Bisphosphonates in multiple myeloma. Cochrane Database Syst Rev. 2001;CD003188. [Medline].

  90. Bloomfield DJ. Should bisphosphonates be part of the standard therapy of patients with multiple myeloma or bone metastases from other cancers? An evidence-based review. J Clin Oncol. Mar 1998;16(3):1218-25. [Medline].

  91. Ludwig H, Fritz E, Kotzmann H, Höcker P, Gisslinger H, Barnas U. Erythropoietin treatment of anemia associated with multiple myeloma. N Engl J Med. Jun 14 1990;322(24):1693-9. [Medline].

  92. Wilson J, Yao GL, Raftery J, Bohlius J, Brunskill S, Sandercock J, et al. A systematic review and economic evaluation of epoetin alpha, epoetin beta and darbepoetin alpha in anaemia associated with cancer, especially that attributable to cancer treatment. Health Technol Assess. Apr 2007;11(13):1-202, iii-iv. [Medline].

  93. Parikh GC, Amjad AI, Saliba RM, Kazmi SM, Khan ZU, Lahoti A, et al. Autologous hematopoietic stem cell transplantation may reverse renal failure in patients with multiple myeloma. Biol Blood Marrow Transplant. Jul 2009;15(7):812-6. [Medline].

  94. Chang ET, Canchola AJ, Cockburn M, et al. Adulthood residential ultraviolet radiation, sun sensitivity, dietary vitamin D, and risk of lymphoid malignancies in the California Teachers Study. Blood. Aug 11 2011;118(6):1591-9. [Medline]. [Full Text].

 
Previous
Next
 
Amyloidosis infiltrating the tongue in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
Radiograph of the skull demonstrating a typical lytic lesion in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
Bone marrow aspirate demonstrating plasma cells of multiple myeloma. Note the blue cytoplasm, eccentric nucleus, and perinuclear pale zone (or halo). All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
Bone marrow biopsy demonstrating sheets of malignant plasma cells in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.