Myeloma and MGUS

Myeloma and Monoclonal Gammopathy of Undetermined Significance (MGUS)

Multiple myeloma generally presents in those aged 60 or more, with a higher incidence in people of black ethnicity. It can be a difficult cancer to identify, especially in its early stages, often presenting with vague symptoms, with multiple other differentials. However, if blood tests are normal, myeloma is unlikely and other causes of the symptoms should be considered, including HIV.

Baseline tests and investigations should be repeated if a person’s condition remains concerning and unexplained following investigation for other causes – combined with safety netting advice for the patient and consideration of further assessment including referral to non-specific pathways, depending on symptomatology.

Clinical features at presentation include bone pain, symptoms of anaemia, renal impairment (e.g. fatigue, pruritus without rash) and symptoms of hypercalcaemia (e.g. constipation, confusion, polyuria, or polydipsia).

Please note that – unlike CRP – an ESR will be raised with a paraprotein so important to remember as a first line test. Consider FBC, plasma viscosity or ESR, renal function and calcium blood tests, particularly if aged 60 years or over, with any of the following unexplained features:

• Bone pain, particularly bony back pain
• Fractures (pathological or fragility), or bone imaging reported as being suggestive of myeloma
• Fatigue
• Polyuria, polydipsia
• Peripheral neuropathy
• Recurrent infection (e.g. blood stream infection, pneumonia).

The CRAB features of myeloma are:

• Raised Calcium
• Renal impairment (unexplained)
• Anaemia (unexplained)
• Bone pain.

Immunoglobulin and Paraprotein Testing

Further testing will depend on the clinical scenario. It may be that immunoglobulin testing is not part of early investigation in a young person without red flag symptoms. Please also consider that myeloma is unlikely if the initial bloods (see above) are normal. However delayed diagnosis is an issue in myeloma as symptoms may be vague in the early stages, making it a difficult cancer to diagnose. There will be some higher risk patients (and those with red flags) where immunoglobulin testing should be done initially, or early on.

If there is high suspicion or red flags on presentation, please test for all the following:

• serum immunoglobulins AND
• serum protein electrophoresis AND
• urinary Bence Jones Proteins.

There is a GPOC / ICE field for myeloma tests that includes all these.

Note that serum free light chains (sFLCs) are not currently routine in NHS Lothian but may have been done for other reasons or on haematologists’ advice. 

Please see the RefHelp guide to paraprotein for further information on interpretation.  Separate guidance on immunoglobulin testing is also available, but note that raised immunoglobulins in the absence of a paraprotein (checked by requesting protein electrophoresis) does not suggest myeloma.

Monoclonal Gammopathy of Undetermined Significance (MGUS)

MGUS (the presence of an isolated paraprotein) is not cancer and is a common incidental finding in the elderly (8.9% of people over 85 years of age). MGUS can progress to myeloma or indeed lymphoma at a rate of 1% per year. Monitoring of patients with MGUS should be considered after shared decision-making, taking into account the risk, benefits, and limitations of further surveillance.  For those who are frail with a small chance of progression in a lifetime, then referral for monitoring is unlikely to be indicated, though it may be that the GP notes are flagged to signal a theoretical future risk. If appropriate, refer all patients with newly identified paraproteins to haematology  in line with the RefHelp paraprotein guidance, which also outlines initial testing.

C.M. – 1-04-26