AKT · Haematology/Haemato-oncology

Multiple myeloma

Malignant clonal plasma-cell proliferation → monoclonal paraprotein + end-organ damage

Overview

A malignancy of plasma cells producing a monoclonal immunoglobulin (paraprotein) and causing end-organ damage summarised by CRAB: hyperCalcaemia, Renal impairment, Anaemia, Bone lesions (lytic). It affects older adults and presents with bone pain/fractures, anaemia, renal failure or recurrent infection. Diagnosis combines paraprotein (serum/urine electrophoresis, free light chains), marrow plasmacytosis and end-organ damage.

Recognise

CRAB: hyperCalcaemia (thirst, confusion, constipation), Renal impairment (cast nephropathy/light chains), Anaemia (marrow infiltration), Bone lesions — lytic 'punched-out' lesions, pathological fractures, back pain, cord compression
Older adult; recurrent infections (immunoparesis), hyperviscosity, raised ESR; Bence-Jones protein (urinary free light chains); ROULEAUX on film
X-ray: lytic lesions, 'pepper-pot' skull; raised total protein with a paraprotein band

Red flags

Hypercalcaemia, acute kidney injury, or metastatic spinal cord compression → emergencies
Hyperviscosity (visual disturbance, confusion, bleeding) → plasmapheresis

Differentials & how to tell them apart

MGUS (monoclonal gammopathy of uncertain significance)paraprotein WITHOUT CRAB/end-organ damage or marrow excess — monitor, can progress to myeloma

Other causes of bone lesionsmetastatic carcinoma (often sclerotic in prostate), hyperparathyroidism

Other causes of renal failure/hypercalcaemiabut the paraprotein + CRAB combination points to myeloma

Rouleaux formation (stacked red cells) in myeloma (blood film)
Osaretin / CC BY-SA 4.0 — Wikimedia Commons

Investigations

Serum + urine protein ELECTROPHORESIS (paraprotein/Bence-Jones), serum free light chains; FBC (anaemia, rouleaux), calcium, U&Es (renal), ESR; skeletal survey/whole-body MRI or CT (lytic lesions); bone marrow (clonal plasma cells); beta-2 microglobulin for staging.

Management

Supportive (hypercalcaemia/renal/bone) + systemic anti-myeloma therapy ± stem-cell transplant

1Suspect from CRAB features in an older adult; confirm with serum/urine electrophoresis + free light chains, marrow plasmacytosis and imaging for lytic lesions. Treat the CRAB complications.Gate: Hypercalcaemia, AKI (cast nephropathy), cord compression or hyperviscosity are emergencies; a paraprotein WITHOUT CRAB/end-organ damage is MGUS (monitor), not myeloma.
2Systemic anti-myeloma therapy (proteasome inhibitor/immunomodulator/steroid ± anti-CD38), autologous stem-cell transplant in eligible patients, bisphosphonates and supportive care.

Supportive: treat hypercalcaemia (IV fluids + bisphosphonate), renal protection, bisphosphonates for bone disease, analgesia, treat infection — manage the CRAB complications and emergencies

Systemic anti-myeloma therapy (proteasome inhibitors, immunomodulators, steroids, anti-CD38) — e.g. bortezomib-based regimens; not curable but very treatable

Autologous stem-cell transplant — for eligible/fitter patients after induction

Treat cord compression urgently — dexamethasone + radiotherapy/surgery

Key points

Older adult + CRAB (hyperCalcaemia, Renal impairment, Anaemia, Bone lytic lesions/back pain) + paraprotein + Bence-Jones + rouleaux = multiple myeloma → electrophoresis + free light chains + marrow + skeletal imaging. Emergencies: hypercalcaemia, AKI, cord compression, hyperviscosity. Paraprotein without CRAB = MGUS (monitor).

Monitor & prognosis

Paraprotein/free light chains, calcium/renal function, bone disease, treatment response/relapse.

Not curable but increasingly treatable with prolonged survival; relapsing-remitting.

Source: NICE NG35 (myeloma); cross-ref renal (cast nephropathy), endocrine (hypercalcaemia), MSK (cord compression/bone)