The evolution of 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 found in some patients presents an asymptomatic clinical stage that sits 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 a lot 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]

Complexity of multiple myeloma

In symptomatic MM, malignant plasma cells undergo clonal expansion in the bone marrow.[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 (the normal ratio for FLC-kλ is 0.26–1.65).[4][9] Some patients with MGUS (~one third) or smouldering MM (~70%) 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]

Pathogenesis of multiple myeloma

Learn about the pathological effects of MM, including elevated calcium, renal failure, anaemia and bone lesions (collectively known as 'CRAB' symptoms[2]), and infections like pneumonia.[12] The underlying genetic mechanisms that lead to tumour heterogeneity and ultimately disease progression will be discussed in this video, highlighting why the heterogeneous nature of MM makes treatment very challenging.[4][7][10]

Epidemiology of multiple myeloma

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]

12 deaths

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]


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]

Age at diagnosis

Age at diagnosis


Men are at a slightly increased risk of developing MM compared with women.[16][17][18][19]


MM is approximately twice as common among black patients as white patients.[18][19] Black patients have lower overall survival compared with white patients.[20]

Find out more

Focusing on Diagnosis

Early diagnosis is critical in MM.[21] An array of diagnostic methods can be used to characterise a patient’s MM, allowing for individualised treatment and management.

Response Measurements

The right treatment plan can improve a patient's response. Find out how treatment response is measured and what strides are being taken to optimise it.


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CP-275046 - May 2022