Multiple Myeloma

Multiple myeloma is an incurable hematologic cancer of plasma cells characterized by increased monoclonal (M) protein levels in the serum and/or urine due to proliferation of malignant clonal plasma cells.1-4 The exact cause of multiple myeloma is unknown.2 Plasma cells transform into malignant myeloma cells through the acquisition of genetic events, activation of key signaling pathways, and aberrant stromal and cellular signaling.5-12 Aberrant expression and/or over expression of key transcription factors and proliferative factors facilitate this malignant process.5,9,10

The pathopysiology of multiple myeloma is characterized by promotion of immune dysregulation, malignant plasma cell survival, and aberrant stromal-cell support.5,13-17


The clinical manifestations of multiple myeloma include renal impairment, anemia, calcium elevation, and bone lesions.1 Monoclonal plasma cells proliferate in the bone marrow and are capable of invading adjacent bone, resulting in bone pain, fractures and skeletal destruction.1,2 Patients commonly present with anemia (more than two-thirds pf patients) and renal impairment (one-fifth of patients).1 Multiple myeloma is associated with regrowth of residual tumor and immune suppression.18,19 Multiple myeloma cells are able to evade detection by the immune system through altering their phenotype and simultaneously inducing the production of immune-suppressing cytokines and other molecules.19

The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated

References

  1. International Myeloma Working Group. Br J Haematol. 2003;121:749-757.
  2. Kyle RA, et al. Best Pract Res Clin Haematol. 2007;20:637-664.
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  6. Raab MS, et al. Lancet. 2009;374:324-339.
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  12. Leung-Hagesteijn C, et al. Cancer Cell. 2013;24:289-304.
  13. Zheng MM, et al. PLoS ONE. 2013;8:e58504.
  14. Bernal M, et al. Hum Immunol 2009;70:854-857.
  15. Holien T, et al. Blood. 2012;120:2450-2453.
  16. Braga WM, et al. Clin Dev Immunol. 2012;2012:293479.
  17. Damiano JS, et al. Blood. 1999;93:1658-1667.
  18. Corradini P, et al. Blood. 2003;102:1927-1929.
  19. Cook G, et al. Blood Rev. 1999;13:151-162.