What causes myeloma?

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How does myeloma develop?

We know that multiple myeloma develops when genetic “errors” occur in the DNA of plasma cells (a type of white blood cell produced in the bone marrow). This error causes the plasma cells to multiply uncontrollably and overproduce a type of antibody called immunoglobulin. When this happens, these rogue plasma cells become myeloma cells and crowd out healthy blood cells in the bone marrow, affecting different parts of the body.

We don’t yet fully understand why these errors occur.
However, there is a tremendous amount of work being devoted to searching for the cause.

While we may not have all the answers regarding what causes myeloma, research suggests possible associations between myeloma and a decline in immune function, as well as genetic and environmental factors.

Having 1 or more risk factors does not mean a person will definitely develop myeloma. Current research suggests that myeloma develops as a result of complex interactions between several factors.


Myeloma risk factors

  • Age is the single most significant risk factor for multiple myeloma
  • 96% of diagnoses are in people over the age of 45
  • The average age at diagnosis is mid-sixties
  • 75% of cases involve people over the age of 70
  • Myeloma is NOT inherited in the same way as some other diseases (such as those caused by a single inherited gene)
  • There is a slightly higher incidence of myeloma among first-degree relatives (ie, parents, siblings, and children)
  • Some inherited genetic “errors” can increase the likelihood of developing myeloma, but these have a very small effect


Your risk of developing myeloma is higher if you have:

  • been diagnosed with MGUS (Monoclonal Gammopathy of Undetermined Significance) or SMM (Smouldering Multiple Myeloma)
  • a history of solitary plasmacytomas of the bone
  • an autoimmune condition; this may place you at a slightly higher risk


Myeloma is slightly more common in men than in women

There are higher incidences of myeloma within the Black population, with males being at higher risk than females of developing the disease

  • Exposure to large amounts of radiation (Agent Orange), and/or certain agricultural and industrial chemicals including:
    • Herbicides
    • Insecticides
    • Petroleum products
    • Heavy metals
    • Various dusts (ie, asbestos, benzene, coal, wood dust)
  • Higher-than-average risk occupations:
    • Agriculture workers
    • Petroleum workers, machinery production workers
    • Carpentry and leather industry workers
    • Firefighters
Une jeune femaile doctor talks with an older male patient

Precursors of myeloma

Conditions such as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Multiple Myeloma (SMM) are typically asymptomatic and may be precursors to active (or symptomatic) myeloma. A history of solitary plasmacytomas may also be a precursor to the disease.

What is MGUS?

MGUS, a condition that may progress to SMM and/or myeloma, affects the production of normal plasma cells in the bone marrow. Abnormal plasma cells—myeloma cells—are produced instead, leading to the overproduction of abnormal clones of
1 type of antibody called a monoclonal antibody or M-protein (also referred to as paraprotein, myeloma protein, or M-spike).

In most people, MGUS is asymptomatic, meaning that you will not experience any symptoms and no treatment is required. There is a small risk, approximately 1% per year, that MGUS could progress to a disease that would require active treatment.

There are 3 main types of MGUS, which are categorized by the type of antibody involved:


Non-IgM MGUS: an antibody other than IgM is affected. This is the most common type of MGUS, and the heavy chain part of the antibody is usually IgG or IgA;


IgM-MGUS: the heavy chain part of the affected antibody is IgM;


Light chain MGUS: the light chain part of the antibody (kappa or lambda) is affected instead of the heavy chain.
Knowing what type of MGUS you have can help identify your potential risk of progression and help you manage your condition most effectively.

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What is SMM?

SMM, or Smouldering Multiple Myeloma, is a second intermediate stage between MGUS and myeloma. As with MGUS, most people with SMM are asymptomatic.

The main difference between MGUS and SMM is the number of myeloma cells in the bone marrow. In people with SMM, this is between 10% and 60%. Individuals living with SMM do not have CRAB symptoms.

The risk of progression from SMM to myeloma is approximately 10% per year for the first 5 years. Due to this higher risk of progression, most people spend less time in the SMM stage (compared to MGUS) and present to their healthcare team when either symptoms begin to become apparent or when activity is detected, during routine blood tests.

MGUS and Smouldering Multiple Myeloma

Learn more about MGUS and SMM in the MGUS and Smouldering Multiple Myeloma InfoGuide.

Solitary plasmacytoma

Sometimes, myeloma cells collect in a single bone and form a tumour called a solitary plasmacytoma of the bone.

Occasionally, a plasmacytoma can affect areas of soft tissue outside of the bone and bone marrow (called an extramedullary plasmacytoma).

Both types of plasmacytoma are most often treated with radiation therapy; however, the majority of people with plasmacytoma of the bone eventually do develop active myeloma.


Multiple Myeloma Patient Handbook

For more information, download the Multiple Myeloma Patient Handbook

Designed to provide educational support to those living with myeloma, their caregivers, families, and friends, this handbook gives accurate, reliable, and clear information on myeloma. Among topics are in-depth discussions on what myeloma is, its causes and effects, treatment options in Canada, and how to manage your myeloma journey.