Aetiology

The aetiology of multiple myeloma (MM) is unknown but most cases evolve from monoclonal gammopathy of undetermined significance (MGUS), a benign pre-malignant condition. (1)

The risk of progression of MGUS to MM (or related disorders) is approximately 1% per year (2)

The origin of the malignant clone in myeloma is the subject of debate but multistep genetic and microenvironmental changes appears to be responsible for the differentiation into malignant plasma cells (3).

The proliferating cells in myeloma occur principally in the bone marrow causing diffuse infiltration and localised solid tumours.

The myeloma cells secrete an osteoclast stimulating factor that leads to marked bone erosion.

The main sites for myeloma involvement are the proximal long bones, the pelvis, the thoracic cage, the vertebral column and the skull.

Risk factors thought to be responsible for multiple myeloma include: (4)

• increasing age
• male gender
• Afro-Caribbean ethnic groups
• positive family history - an increased risk of developing multiple myeloma was observed in 1st-degree relatives of patients with multiple myeloma
• obesity - an elevated relative risk have been reported in a few epidemiologic studies
• diet - low fish and green vegetable consumption
• other risk factors thought to be associated with multiple myeloma but lack consistent data are - hair dye use, wood dust or wood exposures, chronic immune stimulation conditions and/or vaccinations for such conditions

Reference:

1. Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009 May 28;113(22):5412-7.
2. Kyle RA, Larson DR, Therneau TM, et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Engl J Med. 2018 Jan 18;378(3):241-9.
3. Pasca S et al. KRAS/NRAS/BRAF Mutations as Potential Targets in Multiple Myeloma. Front Oncol. 2019;9:1137
4. Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. Ann Oncol. 2021 Mar;32(3):309-22.