About Multiple Myeloma

In the majority of patients MM evolves from an asymptomatic pre-malignant precursor known as monoclonal gammopathy of undetermined significance (MGUS).^[2]

^{Adapted from Kyle et al. 2007, [3] Rajkumar et al. 2014[4] and Mateos et al. 2018[5]
MGUS, monoclonal gammopathy of undetermined significance; MM, Multiple Myeloma; SMM, smouldering Multiple Myeloma}

Smouldering Multiple Myeloma

Smouldering MM presents an asymptomatic clinical stage that is situated between MGUS and active MM.^[2] The estimated incidence of smouldering MM is between 0.4 and 0.9 cases per 100,000 people.^[6]

Rate of progression

While approximately 1% of MGUS cases progress to MM per year, the rate of progression for smouldering MM is much higher – overall about 10% of patients per year progress within 5 years of diagnosis.^[3][4] The risk of progression from smouldering MM to active disease varies between patients, and they can be grouped as being at low-, intermediate- or high-risk of progression.^[5]

In symptomatic MM, malignant plasma cells undergo clonal expansion in the bone marrow.^[4][7] In almost all cases of MM (97%), these plasma cells secrete a monoclonal immunoglobulin – referred to as the M-protein.^[8] A very small percentage of patients, however, will have a non-secretory form of the disease.^[8]

Abnormal free light chain (FLC) ratio

The proliferating clonal plasma cells also produce an excess of either κ or λ light immunoglobulin chains, which circulate freely in the serum, unbound to heavy chains.^[9] This over-production of one free light chain (FLC) – known as the involved FLC – leads to an abnormal FLC ratio.^[4][9] Some patients with MGUS or smouldering MM show altered FLC ratio, which is related to risk of progression of MM.^[4]

The development of genetic abnormalities leads to the proliferation of abnormal plasma cells that may result in heterogeneous tumour cell clusters at multiple sites.^[10][11]

MM represents 1% of all cancers diagnosed in Europe and approximately 10% of haematological malignancies.^[2][13]

Even though survival rates are increasing, MM remains an incurable disease.^[14] Global 5-year survival rates are now about 50–60% in patients aged 65–70 years or younger.^[15]

Mortality rates

Worldwide, around 106,000 people die each year – 12 people every hour – from this disease.^[16] In 2018, 30,900 people died from MM in Europe alone.^[13]

Age, gender & race

The median age at diagnosis for MM is 69 years.^[17] The majority of people are first diagnosed when they are 65 years of age or older, while about one-third of newly diagnosed patients are at least 75 years of age.^[1] Men are at a slightly increased risk of developing MM compared with women.^{[15][16][17][18]}. MM is approximately twice as common among dark-skinned patients as white patients.^[18][19] dark-skinned patients have lower overall survival compared with white patients.^[20]