MGUS/Myeloma/AL Amyloidosis

Introduction

An M-protein (also referred to as a paraprotein) is a monoclonal immunoglobulin secreted by an abnormal clone of plasma cells in an amount that can be identified by immunofixation of serum and/or urine (if it is leaking into the urine). The M-protein is then quantified by electrophoresis which is also used to follow up over time. M-proteins can be whole immunoglobulins (Ig) or just immunoglobulin free light chains (best confirmed by serum free light chain or Bence Jones protein testing).
M-protein related disorders encompass a wide spectrum of problems from an incidental finding that will be of no consequence to the patient and is very common (eg a small paraprotein in an elderly patient) to a life threatening emergency.
Serum protein electrophoresis (SPEP) should be performed if there is clinical suspicion of an M-protein related disorder causing end-organ damage. Signs or symptoms may include:
- New bone pain or lytic lesions on xray
- Unexplained anaemia
- Unexplained hypercalcaemia
- Unexplained renal failure
- Recurrent infections
- M-protein with reduction of other immunoglobulin classes (immune paresis) eg IgG M-protein with low IgA and IgM (polyclonal increase in immunoglobulins is most likely caused by chronic inflammatory or infective processes and does not indicate a primary haematological pathology).

A raised PV can be seen with large M-proteins but is non-specific. If a myeloma screen is carried out for this reason and is negative then another cause for the raised PV should be sought.

IgM paraproteins can occasionally be associated with some forms of lymphoma rather than myeloma, and additional symptoms to look out for include:
- Unexplained weight loss
- Night sweats
- Symptoms of hyperviscosity (eg mucosal bleeding, blurred vision, headache or dizziness)

AL amyloidosis is a rare condition where abnormal light chain clump together and are deposited in organs. Amyloidosis is rare and easily missed. Please think of this if a patient presents with otherwise unexplained nephrotic syndrome, heart failure or progressive peripheral neuropathy.

FBC, renal function, LFTs, calcium, protein electrophoresis, urine for Bence Jones protein (we will advise if we feel serum free light chain testing needed in borderline cases)
If bone pain is the main presentation please consider plain x-rays or other imaging whilst awaiting blood results.

Signs, symptoms or laboratory features suggestive of myeloma, hyperviscosity or AL amyloidosis as outlined above, plus a paraprotein or BJP.

If no signs/ symptoms of end-organ damage, patients with an IgM or IgA band >10g/L, or IgG band of >15g/L, Bence Jones proteinuria (any amount if urine protein:creatinine ratio raised) or nephrotic range proteinuria without a clear cause.
- Refer lower level paraproteins/ BJP if unsure or any concerns. We may offer clinical advice rather than seeing these patients.
- For well patients with low level paraproteins, especially if elderly or coming to clinic would be a logistical challenge, repeating serum electrophoresis/BJP at 3 months initially, and then annually thereafter in the community is appropriate. The overall risk of progression of MGUS to myeloma is approximately 1% per year.

Asymptomatic patients who are having paraprotein monitoring in the community and have had an increase in their paraprotein level by more than 25% in 6 months (a minimum absolute increase of 5g/L).

For well patients with low level paraproteins, especially if elderly or coming to clinic would be a logistical challenge, repeating serum electrophoresis/BJP at 3 months initially, and then annually thereafter in the community is appropriate. The overall risk of progression of MGUS to myeloma is approximately 1% per year.

Further information on investigations/ monitoring of newly detected M-proteins can be found here: