PassFinals
Haematology & Oncology

Myeloma

A clonal plasma-cell malignancy produces monoclonal immunoglobulin or light chains and damages bone, kidneys, marrow and immunity; diagnosis and treatment depend on a myeloma-defining event, disease biology, fitness and patient priorities.

In a nutshell

Multiple myeloma is a clonal plasma-cell malignancy causing paraprotein or light-chain disease and CRAB complications. Confirm a plasma-cell clone and a myeloma-defining event, then stage, assess fitness and treat through a specialist MDT.

Classic presentation

An older adult with persistent back or bone pain, anaemia, renal impairment, hypercalcaemia or recurrent infection; a normal plain X-ray does not exclude myeloma.

Key points

  • CRAB means attributable hypercalcaemia, renal impairment, anaemia or bone disease; SLiM biomarkers can define active disease before CRAB injury.
  • Active myeloma requires clonal marrow plasma cells of at least 10% or a plasmacytoma plus a myeloma-defining event; an isolated paraprotein is not enough.
  • SLiM includes clonal marrow plasma cells of at least 60%, an involved-to-uninvolved free-light-chain ratio meeting the myeloma-defining threshold, or more than one focal MRI lesion.
  • For suspected myeloma in adults aged 60 or over with persistent bone pain or unexplained fracture, NICE recommends FBC, calcium, plasma viscosity or ESR, serum protein electrophoresis and serum free light chains.
  • Whole-body MRI, low-dose CT or FDG PET-CT is preferred to a routine skeletal survey for modern diagnostic and monitoring pathways.
  • Acute kidney injury, severe hypercalcaemia and spinal cord compression require immediate specialist management; do not delay urgent anti-myeloma treatment for renal disease.
  • Treatment is risk- and fitness-adapted: transplant suitability is not decided by age or renal impairment alone.

First-line investigation

Serum protein electrophoresis and serum free light chains with FBC, calcium and renal function, followed by marrow assessment and advanced whole-body imaging.

Management

Recognise and stabilise complications

  • Escalate acute kidney injury, severe hypercalcaemia, pathological fracture, sepsis, hyperviscosity or neurological signs of spinal cord compression to haematology and the relevant emergency team.1,9,3

Confirm the plasma-cell disorder

  • Use serum protein electrophoresis, serum free light chains, immunofixation when indicated, marrow pathology, cytogenetics and advanced imaging to distinguish active myeloma from MGUS or smouldering myeloma.1,2,8

Choose risk- and fitness-adapted therapy

  • Use current NICE options for transplant-suitable or transplant-unsuitable disease, with specialist protocol and BNF checks for regimen, contraindications and dose adjustments.1,11,12,13,5,10

Protect bone, kidney and immune function

  • Offer an appropriate bisphosphonate, arrange dental assessment, prevent treatment-associated thrombosis, manage pain and fractures, and provide infection prevention and symptom support through the myeloma team.1,9,10

Escalate high-risk or relapsed disease

  • Use risk-adapted specialist strategies for high-risk biology, and refer early for relapse-specific combinations, cellular therapy, transplant, clinical trials or palliative care.4,15,1

Monitor response and late effects

  • Review symptoms, toxicity, FBC, renal function, bone profile, immunoglobulins, electrophoresis and free light chains at least three-monthly after completed treatment, using symptom-directed advanced imaging rather than routine skeletal surveys.1,3

Exam traps

  • Do not use serum electrophoresis, serum free light chains or urine Bence-Jones testing alone to exclude myeloma.
  • MGUS and smouldering myeloma are not automatically treated; active myeloma requires attributable organ damage or a validated myeloma-defining biomarker.
  • A normal isotope bone scan or plain skeletal survey does not rule out lytic myeloma bone disease.
  • Do not use plasma exchange for myeloma-induced acute renal disease.
  • Do not give routine pre-biopsy corticosteroids when safe, because they can reduce diagnostic tissue; suspected spinal cord compression is a specialist emergency.
  • Bisphosphonates require renal, dental and jaw-risk assessment; urgent anti-myeloma treatment should not be delayed unnecessarily for dental work.

Illustrations

Bone marrow aspirate in multiple myelomaBone marrow aspirate showing an excess of abnormal plasma cells in multiple myeloma.Nephron, Wikimedia Commons · CC-BY-SA-3.0
CRAB mechanism diagramDiagram showing the plasma-cell clone driving osteoclast activation, light-chain nephrotoxicity and marrow crowding to produce the CRAB features.PassFinals · original
Serum protein electrophoresisElectrophoresis strip and densitometry trace showing a monoclonal band in the gamma region.PassFinals · original
Lytic bone lesions of multiple myelomaRadiograph showing multiple well-defined lytic lesions characteristic of myeloma bone disease.Hellerhoff, Wikimedia Commons · CC-BY-SA-3.0

Key sources

  1. NICE, Myeloma: diagnosis and management (NG35)
  2. British Society for Haematology and UK Myeloma Forum, Guidelines on the diagnosis, investigation and initial treatment of myeloma
  3. NHS, Treatment for myeloma
  4. British Society for Haematology and UK Myeloma Society, Diagnosis and initial treatment of transplant-eligible high-risk myeloma patients
  5. UK Myeloma Research Alliance Frailty Group, Assessment and treatment of frail patients living with multiple myeloma
  6. NICE, Suspected cancer: recognition and referral (NG12)
  7. NHS, Tests and next steps for myeloma
  8. British Society for Haematology and UK Myeloma Society, Advanced imaging for earlier diagnosis and morbidity prevention in multiple myeloma
  9. NICE, Spinal metastases and metastatic spinal cord compression (NG234)
  10. British National Formulary, online prescribing information
  11. NICE, Daratumumab in combination for untreated multiple myeloma when a stem cell transplant is suitable (TA763)
  12. NICE, Daratumumab with lenalidomide and dexamethasone for untreated multiple myeloma when a stem cell transplant is unsuitable (TA917)
  13. NICE, Isatuximab in combination for untreated multiple myeloma when a stem cell transplant is unsuitable (TA1098)
  14. NICE, Lenalidomide maintenance treatment after an autologous stem cell transplant for newly diagnosed multiple myeloma (TA680)
  15. British Society for Haematology and UK Myeloma Society, Management of relapsed multiple myeloma

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.