Multiple Myeloma

Related Subjects: |Hypercalcaemia |Multiple Myeloma |Extramedullary Plasmacytoma |Smouldering Myeloma |MGUS |Waldenstrom Macroglobulinaemia |Oncological emergencies

🔎 Always think of myeloma in a patient with bone pain, raised calcium, or an unexplained high ESR.

📘 About

• Malignant tumour of plasma cells (B-cell lineage).
• Produces monoclonal immunoglobulin (usually IgG or IgA) or light chains (Bence–Jones proteins).
• Median survival ~2–3 years (improving with newer therapies).

📊 Incidence

• ~5,500 new cases per year in the UK 🇬🇧.
• Incidence ~5.4/100,000/year; more common in men.
• Twice as common in patients of African descent.

📈 Spectrum of Plasma Cell Disorders

• MGUS (Monoclonal Gammopathy of Undetermined Significance): Asymptomatic, low paraprotein, no organ damage. ~1% per year progress to myeloma. Managed with monitoring only 🩺.
• Smouldering Myeloma: Higher paraprotein and marrow plasma cells, but still no CRAB features. Requires close observation 👀.
• Multiple Myeloma: Full-blown disease with monoclonal protein + ≥1 CRAB feature (end-organ damage).

💡 CRAB = HyperCalcaemia, Renal impairment, Anaemia, Bone lesions.

⚙️ Aetiology & Pathophysiology

• Uncontrolled plasma cell clone infiltrates marrow → cytopenias.
• Secretion of abnormal immunoglobulins → hyperviscosity & renal failure.
• Suppression of normal immunoglobulins → immunodeficiency 🔻.
• Plasma cell proteins stimulate osteoclasts → lytic bone disease & fractures 🦴.
• Light chains damage kidneys → cast nephropathy.

🧑‍⚕️ Clinical Features

• Age >60, male > female.
• Bone pain (esp. back, ribs, skull); vertebral collapse → cord compression.
• Renal impairment (light chain nephropathy).
• Infections due to low normal immunoglobulins (immunoparesis).
• Anaemia → fatigue, pallor.
• Hypercalcaemia → thirst, confusion, constipation.
• AL Amyloidosis: neuropathy, restrictive cardiomyopathy, nephrotic syndrome, macroglossia 👅.
• Hyperviscosity syndrome (IgA myeloma): blurred vision, headaches, bleeding.

🧪 Investigations

• FBC: Normocytic anaemia, cytopenias.
• Biochemistry: ↑ ESR, ↑ calcium, ↑ urate, ↑ LDH.
• Renal function: may show AKI or CKD.
• Serum protein electrophoresis & urine for BJP: Monoclonal paraprotein.
• Bone marrow aspirate/biopsy: >10% clonal plasma cells; FISH for cytogenetics.
• Imaging: Whole-body MRI, CT or PET-CT for lytic lesions.
• Prognosis: β2-microglobulin ↑ = poor prognosis.

🩸 CRAB Mnemonic

• 🟠 Hypercalcaemia: Ca²⁺ >2.75 mmol/L.
• 🟣 Renal failure: CrCl <40 ml/min or creatinine >177 µmol/L.
• 🔴 Anaemia: Hb <100 g/L.
• ⚫ Bone lesions: lytic lesions, fractures, osteoporosis.

🚑 Complications

• Pathological fractures & spinal cord compression.
• Hypercalcaemia crisis.
• Renal failure (cast nephropathy).
• Recurrent infections (esp. pneumonia, sepsis).
• Pancytopenia & bleeding.

💊 Management

• Fit / Younger Patients: Bortezomib + thalidomide + dexamethasone → autologous stem cell transplant (ASCT).
• Supportive: Transfusions, bisphosphonates (zoledronate/pamidronate) for bone disease, hydration for hypercalcaemia.
• Pain management: Analgesics, radiotherapy for focal lesions.
• Hyperviscosity: Plasma exchange if symptomatic.
• Prophylaxis: Vaccinations, antibiotics, allopurinol for hyperuricaemia.
• Palliative: Discuss prognosis, goals of care, symptom management.

📌 Key exam pearl: If you see “elderly patient + back pain + renal impairment + hypercalcaemia + raised ESR” → think myeloma until proven otherwise 🚨.

Cases - Multiple Myeloma

• Case 1 - Bone pain & lytic lesions 🦴: A 68-year-old man presents with persistent back pain and fatigue. Exam: spinal tenderness. Bloods: normocytic anaemia, calcium 3.1 mmol/L, creatinine 160 µmol/L. X-ray: “punched-out” lytic lesions in vertebrae. Serum electrophoresis: monoclonal IgG spike. Diagnosis: multiple myeloma with bone disease. Managed with bisphosphonates, chemotherapy (bortezomib/lenalidomide/dexamethasone), and supportive care.
• Case 2 - Renal impairment 🩺: A 72-year-old woman is admitted with confusion and oliguria. Bloods: urea 25 mmol/L, creatinine 480 µmol/L, calcium 2.7 mmol/L. Urine: Bence–Jones proteinuria. Renal biopsy: light chain cast nephropathy. Diagnosis: myeloma kidney. Managed with hydration, chemotherapy, and dialysis if required.
• Case 3 - Recurrent infections 🦠: A 61-year-old man has recurrent pneumonias and sinusitis. Bloods: IgG low, Hb 9.5 g/dL, raised ESR. Serum electrophoresis: monoclonal IgA band. Bone marrow: 20% plasma cells. Diagnosis: multiple myeloma with immunoparesis. Managed with chemotherapy, immunoglobulin replacement, and infection prophylaxis.

Teaching Point 🩺: Multiple myeloma is a malignant plasma cell disorder producing monoclonal immunoglobulins. Classic features = CRAB: - Calcium ↑ (hypercalcaemia) - Renal impairment - Anaemia - Bone lesions Diagnosis requires serum/urine electrophoresis, free light chain assay, and bone marrow biopsy. Treatment = chemotherapy, bisphosphonates, and supportive care.