Myeloma

Cancer of the plasma cells; these are a type of B lymphocyte that produce antibodies

Aetiology

• Median age at diagnosis - 65 years

• Other risk factors include:
• MGUS (annual progression risk ≈1%)
• Smoldering multiple myeloma
• Male sex
• Family history
• Environmental exposure (radiation, chemicals)

Pathophysiology

• Plasma cells are B cells (B lymphocytes) of the immune system that have become activated to produce a certain antibody; they are found in the bone marrow

• Myeloma is a cancer of a specific type of plasma cell where there is a genetic mutation causing it to rapidly and uncontrollably multiply

• These plasma cells produce one type of antibody (immunoglobulin)

• When you measure the immunoglobulins in a patient with myeloma, one of those types will be significantly abundant → monoclonal paraprotein
• More than 50% of the time this is immunoglobulin type G (IgG)
• The ‘Bence Jones protein’ that can be found in the urine of many patients with myeloma is actually a part (subunit) of the antibody called the light chains

How does myeloma affect the body?

• Myeloma bone disease - dysregulation of bone remodelling leads to the typical lytic lesions, usually seen in the spine, skull, long bones and ribs
• There is increased osteoclastic activity without increased osteoblast formation of bone, causing fractures of long bones, vertebral collapse and hypercalcaemia
• Soft tissue plasmacytomas also occur and they are the usual cause of spinal cord compression

• Bone marrow infiltration with plasma cells - results in anaemia, neutropenia, and thrombocytopenia

• Paraprotein secretion - may (rarely) result in symptoms of hyperviscosity
• In addition, there is a reduction in the levels of normal immunoglobulin (immune paresis), contributing to the tendency to contract recurrent infections

• Myeloma renal disease - 30% of patients have renal impairment at diagnosis, due to a number of factors:
• Free light chain secretion leads to deposition in the renal tubules, causing renal impairment by cast nephropathy
• Other factors such as hypercalcaemia, use of non-steroidal anti-inflammatory drugs (NSAIDs) and, rarely, the deposition of AL amyloid can also contribute to renal injury

Clinical Presentation

• Bone pain (back, ribs, hips)

• Fatigue and weakness

• Recurrent infections

• Weight loss

• Pathological fractures

• Pallor

• Bone tenderness

• Vertebral collapse

• Neurologic deficits (cord compression)

Investigations

Hematological Tests

• Normocytic normochromic anemia

• Rouleaux formation on peripheral smear

• ESR markedly elevated

Biochemical Tests

• Hypercalcemia

• Elevated creatinine

• Hypoalbuminemia

• Increased β₂-microglobulin

Myeloma-Specific Tests

• Serum protein electrophoresis (SPEP): M spike

• Immunofixation electrophoresis

• Serum free light chain assay (κ/λ ratio)

• Bence Jones proteins (free light chains)

• 24-hour urine protein electrophoresis

Bone Marrow Examination

• ≥10% clonal plasma cells

• Atypical plasma cells with binucleation

Imaging

• Skeletal survey: punched-out lytic lesions

• MRI spine: cord compression

• PET-CT: disease burden assessment

Diagnostic Criteria

Core Diagnostic Requirement

Myeloma-Defining Events (MDE)

Management

• Myeloma is currently seen as an incurable chronic disease - usually takes a relapsing-remitting course, treatment aims to improve quality of life and prolong survival

Haematopoietic stem cell transplant

• This is a treatment option with young patients who have minimal comorbidities

Chemotherapy

• Combination chemotherapy is the mainstay of treatment
• Thalidomide in combination with an alkylating agent (e.g. melphalan) and a corticosteroid (e.g. dexamethasone) is first line

• Use paraprotein level to monitor response

Symptom control

• Opiate analgesia (avoid NSAIDs)

• Local radiotherapy - good for pain relief or spinal cord compression

• Bisphonates - corrects hypercalcaemia and bone pain

• Vertebroplasty - inject sterile cement into fractured bone to stabilise