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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- CRAB criteria: Calcium elevated, Renal impairment, Anaemia, Bone lesions — define end-organ damage requiring treatment
- Investigations: serum protein electrophoresis (paraprotein/M-band), serum free light chains, urine Bence Jones protein, bone marrow biopsy (≥10% clonal plasma cells)
- Imaging: whole-body low-dose CT or whole-body MRI (preferred over plain X-rays). Lytic "punched-out" lesions; NO isotope bone scan (no osteoblastic activity)
- Treatment: fit patients → VTd induction (bortezomib, thalidomide, dexamethasone) → autologous stem cell transplant → lenalidomide maintenance
- Supportive: bisphosphonates (zoledronic acid) for bone disease, analgesia, renal protection, VTE prophylaxis
Overview
Multiple myeloma is a malignant neoplasm of terminally differentiated B-cells (plasma cells) that produce a monoclonal immunoglobulin (paraprotein). Plasma cells accumulate in the bone marrow, causing bone destruction (lytic lesions and osteoporosis), suppression of normal haematopoiesis (anaemia), and production of dysfunctional immunoglobulin (immunoparesis leading to infection susceptibility). The paraprotein and light chains can cause renal damage (myeloma cast nephropathy). Hypercalcaemia results from osteoclast activation and bone resorption.
Epidemiology
Myeloma is the 17th most common cancer in the UK, with approximately 5,500 new cases per year. The median age at diagnosis is 70 years, and it is very rare under 40. Males are affected slightly more than females (1.5:1). It is twice as common in people of African-Caribbean descent. The diagnosis is often delayed due to non-specific symptoms — median time from first symptom to diagnosis is approximately 5 months.
Clinical Features
Symptoms
Bone pain — the most common presenting symptom (70%), especially lower back and ribs. Pathological fractures
Fatigue and breathlessness (anaemia)
Recurrent infections — especially pneumonia (immunoparesis from suppression of normal immunoglobulins)
Thirst, polyuria, constipation, confusion (hypercalcaemia)
Foamy urine (Bence Jones proteinuria)
Weakness or numbness in legs (spinal cord compression from vertebral collapse)
Peripheral neuropathy (amyloidosis or paraprotein-related)
Signs
Pallor (anaemia)
Bony tenderness (especially spine, ribs, pelvis)
Kyphosis or loss of height (vertebral compression fractures)
Dehydration (hypercalcaemia)
Signs of spinal cord compression (upper motor neurone signs, sensory level)
Macroglossia (AL amyloidosis — rare but characteristic)
Investigations
First-line
Serum protein electrophoresis (SPE)Monoclonal band (M-band/paraprotein) — present in >80%. If abnormal, immunofixation identifies type (IgG most common, then IgA)
Serum free light chains (sFLC)Abnormal kappa/lambda ratio detects light-chain-only myeloma and monitors treatment response. More sensitive than urine BJP
Urine Bence Jones proteinMonoclonal free light chains in urine. Request on all suspected myeloma
FBC, U&Es, Calcium, LDH, albuminAnaemia, renal impairment, raised calcium, raised LDH, low albumin — assess CRAB criteria
Second-line
Bone marrow aspirate and trephineDiagnostic: ≥10% clonal plasma cells. Also for cytogenetics/FISH — essential for risk stratification
Whole-body low-dose CT or whole-body MRINICE NG35 recommends whole-body MRI as first-line imaging. Detects lytic bone lesions, soft tissue plasmacytomas. Superior to skeletal survey
Beta-2-microglobulin and albuminInternational Staging System (ISS): Stage I = B2M <3.5 + albumin ≥35. Stage III = B2M ≥5.5
Specialist
FISH cytogenetics on marrowHigh-risk: t(4;14), t(14;16), t(14;20), del(17p), gain(1q). Standard risk: t(11;14), hyperdiploidy
DO NOT order isotope bone scanMyeloma causes purely LYTIC lesions (osteoclast activation without osteoblast response) — isotope bone scans rely on osteoblastic activity and will be FALSE NEGATIVE
CT headIf "pepper-pot skull" appearance suspected (multiple small lytic lesions)
1
Emergency management
- Hypercalcaemia: aggressive IV fluid rehydration (0.9% NaCl 3-4 L/day) + IV zoledronic acid (4 mg over 15 min)
- Spinal cord compression: emergency MRI, dexamethasone 16 mg/day, urgent radiotherapy/surgery
- Renal failure: rehydration, avoid nephrotoxins, treat hypercalcaemia, consider urgent chemotherapy (bortezomib-based) to reduce light chain burden
2
Transplant-eligible patients (generally <70 and fit)
- Induction: VTd (bortezomib + thalidomide + dexamethasone) for 4 cycles — or VRd (bortezomib + lenalidomide + dexamethasone)
- Stem cell harvest (autologous peripheral blood stem cells after mobilisation with G-CSF)
- High-dose melphalan conditioning followed by autologous stem cell transplant (ASCT)
- Lenalidomide maintenance post-ASCT until progression — improves progression-free and overall survival
3
Transplant-ineligible patients
- VMP (bortezomib + melphalan + prednisolone) or VRd (bortezomib + lenalidomide + dexamethasone) — attenuated doses
- Daratumumab (anti-CD38) increasingly used in combination upfront
- Lenalidomide maintenance
4
Supportive care
- Bisphosphonates: zoledronic acid (4 mg IV monthly) or oral sodium clodronate for ALL patients with bone disease — reduces skeletal events
- VTE prophylaxis: LMWH or aspirin (especially with immunomodulatory drugs — thalidomide, lenalidomide)
- Analgesia for bone pain (WHO ladder); radiotherapy for painful localised bone disease
- Infection prevention: influenza and pneumococcal vaccination, low threshold for antibiotics
- Erythropoietin for symptomatic anaemia if Hb remains low despite treatment
Complications
- Pathological fractures: Vertebral compression fractures, long bone fractures — may present acutely
- Renal failure: Light chain cast nephropathy (commonest), hypercalcaemia, amyloidosis, light chain deposition disease. Occurs in ~20% at diagnosis
- Hypercalcaemia: Affects ~30% — emergency management required
- Spinal cord compression: From vertebral collapse or epidural plasmacytoma — neurological emergency
- Hyperviscosity: Rare, mainly with IgA or IgM (Waldenström) — visual disturbance, confusion, bleeding. Emergency plasmapheresis
- AL amyloidosis: Complicates ~15% of myeloma — cardiac, renal, neuropathic manifestations
UKMLA Exam Tips
- 1CRAB criteria: Calcium raised, Renal failure, Anaemia, Bone lesions — the mnemonic for myeloma end-organ damage
- 2Raised ESR + back pain + normocytic anaemia in an elderly patient = think myeloma
- 3Isotope bone scan is FALSE NEGATIVE in myeloma — purely lytic lesions, no osteoblastic activity. Use CT or MRI
- 4Bence Jones protein = urinary free light chains. A spot test is not sufficient — request a formal Bence Jones quantification
- 5Rouleaux formation on blood film (stacking of red cells) = high paraprotein, think myeloma
- 6"Pepper-pot skull" and lytic "punched-out" lesions on X-ray = classic myeloma imaging findings
- 7Bortezomib is the backbone of myeloma treatment (proteasome inhibitor). Lenalidomide for maintenance
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