Paraproteins and Myeloma Testing in Primary Care

NCL ICB pathway

Paraproteins: an abnormal protein in the blood or urine – secreted by a blood malignancy

Myeloma – a blood cancer associated with anaemia, renal impairment, hypercalcaemia, bone lesions.

MGUS – common in older patients. Precursor condition that can transform into myeloma. Around 1% transformation rate per year. Usually only monitored.

Why check blood and urine for paraproteins?

Intact immunoglobulins are detected using Serum Protein Electrophoresis

Lightchains are detected by Urine Protein Electrophoresis (Bence Jones Protein) – although recently can also be detected in serum as Serum Free Light Chain (SFLC)

How do you interpret SFLC?

If both Kappa and Lambda light chains are elevated, this is usually due to renal impairment, infection or inflammation – this does not require haem review.

If only one the types is elevated, this represents a potential haematological issue.

Someone does paraprotein investigations – how do I interpret the results?

Low level paraproteins without evidence of end organ damage

  • Normal protein electrophoresis, SFLC ratio <0.2 or >3.0
    • possible high risk MGUS – routine haematology referral
  • Abnormal protein electrophoresis (IgG paraprotein <15g/l or non IgG paraprotein <10g/l) + abnormal SFLC ratio
    • possible high risk MGUS – routine haematology referral

  • Normal protein electrophoresis, SFLC ratio 0.2-0.3 or 2.0-3.0
    • low risk MGUS or renal/inflammatory disorder – monitor MGUS in primary care (FBC, U+E, calcium, serum protein electrophoresis and SFLC/urine protein electrophoresis every 6 months) and ask about any new bone pain or recurrent infections
  • Abnormal protein electrophoresis (IgG paraprotein <15g/l or non IgG paraprotein <10g/l) + normal SFLC ratio
    • low risk MGUS or renal/inflammatory disorder – monitor MGUS in primary care (FBC, U+E, calcium, serum protein electrophoresis and SFLC/urine protein electrophoresis every 6 months) and ask about any new bone pain or recurrent infections
  • Consider advice and guidance if
    • SFLC rising/falling significant but still within 0.1 – 10
    • Two consecutive increases in >25% in paraprotein of at least 5g/l

When to refer as two week wait to haematology?

  • High paraprotein levels without evidence of end organ damage
    • > 15g/l IgG paraprotein
    • > 10g/l IgA or IgM paraproteins
    • > 10 SFLC ratio
    • < 0.1 SFLC ratio
    • Free Kappa or Free Lambda >100g/l with any abnormal Kappa/Lambda ratio
    • IgD or IgE paraprotein

–> Refer as 2-week wait to haematology

  • Raised paraprotein and evidence of end organ damage
    • Bloods
      • Low Hb
      • Low platelets
      • Low neutrophils
      • Lowering eGFR
      • Raised calcium
    • B symptoms
      • Weight loss
      • Fevers
      • Night sweats
    • Examination/radiology
      • Persistent LN enlargement (>1cm)
      • Splenomegaly (>15cm)
      • X-ray showing lytic bone lesions

–> Refer as 2-week wait to haematology