Multiple myeloma is characterised by the accumulation of plasma cells in the bone marrow, the presence of M-proteins in serum and urine, and CRAB (hypercalcaemia, renal dysfunction, anaemia, and bone disease) in symptomatic patients.
Multiple myeloma accounts for 1% of all cancers and 10% of hematologic malignancies. 99% of cases occur over 40 years.
Definition of terms
| Term | Definition |
|---|---|
| Smouldering multiple myeloma | An asymptomatic condition characterised by monoclonal gammopathy with no end-organ or tissue damage. Some patients may progress to MGUS and multiple myeloma. |
MGUS vs smouldering myeloma vs multiple myeloma
| MGUS | Smouldering myeloma | Multiple myeloma | |
|---|---|---|---|
| M spike (SPEP) | Yes | Yes | Yes |
| “CRAB” signs | No | No | Yes |
| Plasma cells on bone marrow biopsy | Less than 10% | 10% or more | > 10% |
Revised International Staging System (RISS) for MM
| Stage | Description |
|---|---|
| Stage I | B2-microglobulin <3.5mg/L AND albumin is 3.5g/dL or greater AND standard genetic AND normal LDH levels |
| Stage II | Not stage I or Stage III (in between) |
| Stage III | B2-microglobulin >5.4mg/L AND high-risk cytogenetics |
Diagnostic criteria
- End-organ symptoms or Labs characteristic of multiple myeloma (CRAB)
AND
- Monoclonal protein spike on UPEP or SPEP
AND
- Greater than 10% plasma cells on BM biopsy
- Risk factors
- African
- Male
- Family History of multiple myeloma
- Signs and Symptoms
- Bone pain (70%) and pathologic fractures due to lytic lesions
- Neuropathy due to spinal cord compression
- Symptoms of anaemia
- Recurrent and severe infections due to defective antibodies and neutropenia
- Easy bruising and bleeding due to thrombocytopenia, and interference with coagulation factors and platelet function
- Symptoms of hypercalcaemia
- Macroglossia, carpal tunnel syndrome, subcutaneous nodules, and diarrhea due to amyloidosis in 5%
- Hyperviscosity syndrome (2%)
- Headache
- Visual disturbance
- Confusion
- Neuropathy
- Heart failure
- Investigations
- Peripheral Blood Film
- Abnormal plasma cells (15%)
- Rouleaux formation (due to increased plasma proteins. Need 10 RBCs in a row)
- Bone Marrow Aspirate or Biopsy
- Increased plasma cells with abnormal forms (>10%)
- Immunohistochemistry or Flow cytometry
- CD38+, CD138+, CD45-
- Serum protein electrophoresis (SPEP)
- M-spike in the gamma region – IgG (60%), IgA (20%), Light chains (Kappa or lambda),
- Immune paresis (reduced normal Ig amount)
- Urine protein electrophoresis (UPEP): 24-hour urine collection for Bence Jones proteinuria (2/3)
- Hyperalcaemia
- Elevated Creatinine (20%)
- Low albumin (advanced disease)
- Radiograph and CT-scan for areas with bone pain and fractures +/- a general skeletal survey:
- Lytic bone lesions (’soap bubble appearance”),
- Pathological fractures,
- Vertebral body compression,
- Osteopenia,
- Osteoporosis
- ELevated ESR
- B-2 microglobulin for prognosis
- <3.5 mg = good prognosis
- 5.5 mg = poor prognosis
- FISH
- Hyperdiploidy (>50% of tumours)
- ESR: >100
- Peripheral Blood Film
- Treatment
- Bone marrow transplant for eligible patients (< 65 years without comorbidities)
- Primary induction with bortezomib, cyclophosphamide, and dexamethasone
- Autologous bone marrow transplant
- Maintenance therapy with lenalidomide
- Chemotherapy for patients who are ineligible for bone marrow transplant
- Melphalan, prednisone, and thalidomide
- Correct hypercalcaemia
- Ensure proper hydration
- Prophylactic vaccination
- Erythropoietin for anemia if there is renal failure
- Surgery
- Bone marrow transplant for eligible patients (< 65 years without comorbidities)