Myeloma

Myeloma is primarily a disease of the elderly (median age 70). It is preceded by an asymptomatic phase known as Monoclonal Gammopathy of Undetermined Significance (MGUS). The clinical features arise from: 1) Marrow infiltration (anaemia, pancytopenia); 2) Monoclonal protein production (renal failure, hyperviscosity); 3) Cytokine production leading to osteoclast activation (pathological fractures, hypercalcaemia). The 'M-protein' is usually IgG (60%) or IgA (20%), or Light Chains only (15%). If only light chains are produced, they are filtered by the kidney and appear in the urine as Bence-Jones protein. Diagnosis criteria involve >10% plasma cells on marrow biopsy plus a myeloma-defining event (CRAB features or specific biomarkers). It remains an incurable but treatable condition.

The pathogenesis involves translocation of oncogenes to the immunoglobulin heavy chain locus on chromosome 14. This leads to clonal expansion of plasma cells which occupy and destroy bone marrow space. These cells produce RANK-ligand, which stimulates osteoclasts and inhibits osteoblasts, causing purely lytic bone destruction without new bone formation (hence alkaline phosphatase is usually normal). The excessive production of monoclonal light chains leads to glomerular and tubular damage (cast nephropathy). The cells also suppress normal B-cell function, causing immunodeficiency and recurrent infections.

Presenting features: Bone pain (especially back pain, worse on movement), pathological fractures, lethargy (anaemia), and symptoms of hypercalcaemia (confusion, constipation, polyuria). Recurrent infections (pneumonias/UTIs) are common. Renal failure may be the presenting feature. Hyperviscosity syndrome (headache, visual disturbance) can occur if M-protein levels are very high. Physical signs are often few, but may include pallor, bone tenderness, or signs of amyloidosis (macroglossia, carpal tunnel). Myelopathic features may present if a plasmacytoma causes cord compression.

Bloods: FBC (Anaemia), U&Es (raised creatinine), Calcium (raised), Albumin, LDH, ESR/PV (very high), Serum free light chain assay. Diagnostic: 1) Serum and Urine protein electrophoresis (M-spike and Bence-Jones protein). 2) Bone marrow aspirate and trephine (>10% clonal plasma cells). Imaging: Whole-body MRI or CT (skeletal survey) to look for lytic lesions. Note: Isotope bone scans are NOT helpful as they detect osteoblast activity (which is absent in myeloma).

Acute Management: Hypercalcaemia (IV fluids and Bisphosphonates). Renal failure (hydration, avoid NSAIDs). Cord compression (Dexamethasone and urgent radiotherapy/surgery). Definitive Management: In patients <70 (fit): Induction chemotherapy (e.g., Bortezomib, Thalidomide, Dexamethasone) followed by Autologous Stem Cell Transplant. In patients >70 (less fit): Chemotherapy (e.g., Daratumumab, Melphalan, Prednisolone). Supportive: Bisphosphonates (Zoledronic acid) for all patients to prevent bone events. Yearly flu jab.