Multiple myeloma

Last updated: December 8, 2021

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Multiple myeloma (Kahler disease) is a malignant plasma cell dyscrasia characterized by uncontrolled proliferation and the diffuse infiltration of monoclonal plasma cells in the bone marrow. Plasmacytoma, an early-stage plasma cell dyscrasia, originates from the same type of malignant plasma cells but is characterized by solitary cell proliferation that forms a mass. Malignant plasma cells generally produce monoclonal proteins (also known as M proteins or paraproteins), such as abnormal antibodies (e.g., IgG or IgA) or immunoglobulin light chains (e.g., Bence Jones protein). The condition is most common in elderly patients, who present with unspecific symptoms (fever, night sweats, weight loss), bone pain, or back pain, although multiple myeloma may also be asymptomatic; in this case, it is often a coincidental finding of serum protein electrophoresis. Proliferating plasma cells suppress normal bone marrow function, which leads to clinical findings of anemia, bleeding and/or infection. Additionally, plasma cell proliferation may result in extensive skeletal destruction with hypercalcemia. Complications arising from multiple myeloma often affect the kidneys, leading to conditions such as myeloma cast nephropathy, light chain deposition disease, amyloid light-chain (AL) amyloidosis with renal involvement, and nephrocalcinosis. Younger patients in good general condition are treated with a combination of high-dose chemotherapy and autologous stem cell transplantation, whereas older or frail patients are treated with immunomodulatory drugs (bortezomib, thalidomide, lenalidomide) combined with conventional chemotherapy (melphalan).

Epidemiological data refers to the US, unless otherwise specified.

  • Based on immunoglobulin type [2]
    • IgG and IgA: typical multiple myeloma; majority of patients
    • Bence Jones myeloma (free light chains excreted in urine): 15–20% of multiple myelomas
    • IgD, IgE, and IgM: very rare subtypes of multiple myelomas

International Staging System (ISS) [5]

International Staging System for multiple myeloma

Features Stage I Stage II Stage III
Serum concentration
Median survival
  • > 5 years
  • 3–4 years
  • 2–3 years
  • Often asymptomatic
  • Mild fever, night sweats, weakness, and weight loss
  • Bone pain, especially back pain (most common symptom)
  • Symptoms of hypercalcemia
  • Spontaneous fractures
  • Increased risk of infection
  • Increased risk of petechial bleeding
  • Foamy urine (caused by Bence Jones proteinuria)

Enlarged lymph nodes are not a typical finding.

Approach and diagnostic criteria [6]

Diagnostic criteria [6]
Types Main criterion Plus at least one of the following “myeloma-defining events”
Multiple myeloma

CRAB indicates organ damage: Calcium increased, Renal insufficiency, Anemia, and Bone lesions.

Laboratory tests

Bone marrow biopsy

Imaging [9]

The choice of therapy depends on the outcome of the patient's category, general condition, and eligibility for hematopoietic stem cell transplantation (HSCT).

Other plasma cell dyscrasias

Monoclonal gammopathy of undetermined significance (MGUS) [11][12]

Waldenstrom macroglobulinemia [17]

Overproduction of monoclonal IgM suggests Waldenstrom macroglobulinemia rather than multiple myeloma.

POEMS syndrome

The differential diagnoses listed here are not exhaustive.

Renal disease

Systemic manifestations

We list the most important complications. The selection is not exhaustive.

  • The course of disease and prognosis are highly variable.
  • Therapeutic options have improved significantly. However, complete remission is rare.
  • Poor prognostic factors include
  1. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 Patients With Newly Diagnosed Multiple Myeloma. Mayo Clinic Proceedings. 2003; 78 (1): p.21-33. doi: 10.4065/78.1.21 . | Open in Read by QxMD
  2. Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009; 23 (12): p.2210-2221. doi: 10.1038/leu.2009.174 . | Open in Read by QxMD
  3. Lu J, Lu J, Liu A, et al. The applicability of the International Staging System in chinese patients with multiple myeloma receiving Bortezomib or Thalidomide-based regimens as induction therapy: A multicenter analysis. BioMed Res Int. 2015; 2015 : p.1-7. doi: 10.1155/2015/856704 . | Open in Read by QxMD
  4. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014; 15 (12): p.e538-e548. doi: 10.1016/s1470-2045(14)70442-5 . | Open in Read by QxMD
  5. Schieferdecker A, Hörber S, Ums M, et al. Comparison of three different serum-free light-chain assays—implications on diagnostic and therapeutic monitoring of multiple myeloma. Blood Cancer Journal. 2020; 10 (1). doi: 10.1038/s41408-019-0267-8 . | Open in Read by QxMD
  6. Cooper EH, Plesner T. Beta-2-microglobulin review: Its relevance in clinical oncology. Med Pediatr Oncol. 1980; 8 (4): p.323-334. doi: 10.1002/mpo.2950080403 . | Open in Read by QxMD
  7. Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Annals of Oncology. 2017; 28 (suppl_4): p.iv52-iv61. doi: 10.1093/annonc/mdx096 . | Open in Read by QxMD
  8. Lambert L, Ourednicek P, Meckova Z, Gavelli G, Straub J, Spicka I. Whole-body low-dose computed tomography in multiple myeloma staging: Superior diagnostic performance in the detection of bone lesions, vertebral compression fractures, rib fractures and extraskeletal findings compared to radiography with similar radiation exposure. Oncol Lett. 2017; 13 (4): p.2490-2494. doi: 10.3892/ol.2017.5723 . | Open in Read by QxMD
  9. Therneau TM, Kyle RA, Melton LJ, et al. Incidence of monoclonal gammopathy of undetermined significance and estimation of duration before first clinical recognition. Mayo Clin Proc. 2012; 87 (11): p.1071-1079. doi: 10.1016/j.mayocp.2012.06.014 . | Open in Read by QxMD
  10. Korde N, Kristinsson SY, Landgren O. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies. Blood. 2011; 117 (21): p.5573-5581. doi: 10.1182/blood-2011-01-270140 . | Open in Read by QxMD
  11. Rajkumar SV, Kyle RA, Buadi FK. Advances in the Diagnosis, Classification, Risk Stratification, and Management of Monoclonal Gammopathy of Undetermined Significance: Implications for Recategorizing Disease Entities in the Presence of Evolving Scientific Evidence. Mayo Clinic Proceedings. 2010; 85 (10): p.945-948. doi: 10.4065/mcp.2010.0520 . | Open in Read by QxMD
  12. Go RS, Rajkumar SV. How I manage monoclonal gammopathy of undetermined significance. Blood. 2018; 131 (2): p.163-173. doi: 10.1182/blood-2017-09-807560 . | Open in Read by QxMD
  13. Kyle RA, Durie BGM, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010; 24 (6): p.1121-1127. doi: 10.1038/leu.2010.60 . | Open in Read by QxMD
  14. Dispenzieri A, Kyle R, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2008; 23 (2): p.215-224. doi: 10.1038/leu.2008.307 . | Open in Read by QxMD
  15. Gertz MA. Waldenström macroglobulinemia: 2017 update on diagnosis, risk stratification, and management. Am J Hematol. 2017; 92 (2): p.209-217. doi: 10.1002/ajh.24557 . | Open in Read by QxMD
  16. Hogan JJ, Alexander MP, Leung N. Dysproteinemia and the Kidney: Core Curriculum 2019. American Journal of Kidney Diseases. 2019; 74 (6): p.822-836. doi: 10.1053/j.ajkd.2019.04.029 . | Open in Read by QxMD
  17. Rotaru I, Găman G, Dumitrescu D, Foarfă C. Secondary plasma cell leukemia. Rom J Morphol Embryol. 2012; 53 (4): p.1073-1076.
  18. Markowitz GS. Dysproteinemia and the Kidney. Adv Anat Pathol. 2004; 11 (1): p.49-63. doi: 10.1097/00125480-200401000-00005 . | Open in Read by QxMD

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