• Clinical science

Multiple myeloma


Multiple myeloma (Kahler's 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).



  • Sex: > (3:2) [1]
  • Peak incidence: 50–70 years [1]

Epidemiological data refers to the US, unless otherwise specified.



Clinical features

Enlarged lymph nodes are not a typical finding.


International Staging System (ISS) [3]

International Staging System for multiple myeloma

Features Stage I Stage II Stage III
Serum concentration
  • β2 microglobulin < 3.5 mg/L AND albumin ≥ 3.5 g/dL
  • β2 microglobulin 3.5–5.5 mg/L OR
  • β2 microglobulin < 3.5 mg/L AND albumin < 3.5 g/dL
  • β2 microglobulin ≥ 5.5 mg/L
Median survival
  • > 5 years
  • 3–4 years
  • 2–3 years


Approach and diagnostic criteria [4]

Diagnostic criteria [4]
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 [7]

  • First choice: low‑dose whole body CT (WBLD-CT) [8]
  • Alternatives
    • Skeletal survey: multiple lytic lesions ("punched-out" holes), e.g. in the skull
    • FDG/PET scan: detects areas of active osteolysis
    • MRI: visualizes infiltration and replacement of bone marrow (e.g., in the spine and pelvis)


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

Differential diagnoses

Other plasma cell dyscrasias

Monoclonal gammopathy of undetermined significance (MGUS) [9][10]

  • Definition: : characterized by complete or incomplete monoclonal immunoglobulins (of any class) detectable in patient serum without accompanying clinical symptoms
  • Epidemiology
  • Diagnostic criteria
  • Complications: multiple myeloma (approx. 1% of MGUS cases per year transform into multiple myeloma)
  • Treatment: none required (monitor M-protein levels)

Waldenstrom macroglobulinemia [11]

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

POEMS syndrome

The differential diagnoses listed here are not exhaustive.


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
    • Advanced stage according to the ISS staging system
    • Advanced age
    • β2 microglobulin
    • ↓ Serum albumin
    • CRP
    • LDH
  • 1. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 Patients With Newly Diagnosed Multiple Myeloma. Mayo Clinic Proceedings. 2003; 78(1): pp. 21–33. doi: 10.4065/78.1.21.
  • 2. Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009; 23(12): pp. 2210–2221. doi: 10.1038/leu.2009.174.
  • 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: pp. 1–7. doi: 10.1155/2015/856704.
  • 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): pp. e538–e548. doi: 10.1016/s1470-2045(14)70442-5.
  • 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.
  • 6. Cooper EH, Plesner T. Beta-2-microglobulin review: Its relevance in clinical oncology. Med Pediatr Oncol. 1980; 8(4): pp. 323–334. doi: 10.1002/mpo.2950080403.
  • 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): pp. iv52–iv61. doi: 10.1093/annonc/mdx096.
  • 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): pp. 2490–2494. doi: 10.3892/ol.2017.5723.
  • 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): pp. 1071–1079. doi: 10.1016/j.mayocp.2012.06.014.
  • 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): pp. 5573–5581. doi: 10.1182/blood-2011-01-270140.
  • 11. Gertz MA. Waldenström macroglobulinemia: 2017 update on diagnosis, risk stratification, and management. Am J Hematol. 2017; 92(2): pp. 209–217. doi: 10.1002/ajh.24557.
  • 12. Rotaru I, Găman G, Dumitrescu D, Foarfă C. Secondary plasma cell leukemia. Rom J Morphol Embryol. 2012; 53(4): pp. 1073–1076. pmid: 23303035.
last updated 11/10/2020
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