Background Information
Definition
MM is a haematologic malignancy defined by the presence of abnormal plasma cells within the bone marrow.
Aetiology
Diagnosis
Approach:
- MM should be suspected in >60 y/o patients with persistent bone pain (esp. back pain) or unexplained fracture
- If MM is suspected, offer the following initial investigations:
- FBC
- Calcium level
- ESR
- Serum protein electrophoresis
- Serum free light chain (if not available → urine electrophoresis)
- If the initial investigations are suggestive of MM → suspected cancer pathway referral.
- Secondary care investigations would include:
- Imaging
- Definitive test: bone marrow analysis
Clinical Manifestation (End-Organ Damage)
The CRAB criteria represent the classic manifestation of end-organ damage caused by MM: [Ref]
| Calcium high | Features of hypercalcaemia:
|
| Renal impairment | Often asymptomatic, detected on blood tests
Late manifestations include oliguria / anuria, fluid overload, uraemic symptoms |
| Anaemia | Features of anaemia
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| Bone lesions | Bone lesions in MM include:
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Manifestations beyond the CRAB criteria: [Ref]
- Thrombocytopenia → bleeding / bruising
- MM-related immunodeficiency (B-cell and T-cell dysfunction) → recurrent infections (esp. chest infection)
10-15% of patients with MM have concurrent light chain amyloidosis, which can cause:
- Macroglossia
- Periorbital ecchymoses (panda eyes)
- Submandibular gland enlargement
- Unexplained cardiomyopathy
Laboratory Tests
| FBC |
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| ESR |
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| Bone profile |
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| U&E and metabolic panel |
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| Peripheral blood smear |
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Protein Studies
There are 3 main protein studies: [Ref]
| Serum free light chain assay |
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| Serum protein electrophoresis |
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| 24-Hour urine electrophoresis |
|
Imaging
Imaging should be offered to ALL patients with suspected MM:
- 1st line: whole body MRI
- 2nd line: whole body low-dose CT
- 3rd line: skeletal survey (less sensitive – a lytic lesion only becomes visible on a standard X-ray after 30% to 50% of the bone cortex has been eroded)
Typical imaging findings include: [Ref]
- Osteolytic lesions (at least 1 osteolytic lesion is needed to meet the diagnostic criteria)
- Pathological fractures (esp. vertebrae, ribs)
- Vertebral collapse / compression fractures
Bone Marrow Analysis
Definitive test: bone marrow aspirate + biopsy [Ref]
- ≥10% of bone marrow plasma cells meet the diagnostic criteria
Management
Definitive Management
The first step is to determine if the patient meets the haematopoietic stem cell transplant eligibility, key criteria include: [Ref]
| Adequate organ function |
|
| Acceptable functional status |
|
| Age consideration |
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Transplantation is intensive and generally unsuitable for patients with severe irreversible non-renal organ disease, poor functional status, or significant frailty.
Transplant Eligible
Standard 1st line treatment in transplant-eligible patients is made up of a 3-phase approach:
| Phase 1: induction therapy | NICE recommends bortezomib + dexamethasone +/- thalidomide
Usually given for 3-6 months to rapidly reduce tumour burden in the bone marrow |
| Phase 2: autologous haematopoietic stem cell transplant | A 3-phase process:
|
| Phase 3: maintenance therapy | Low-dose lenalidomide monotherapy |
Transplant Ineligible
Mainstay of management is systemic combination therapy:
- 1st line: thalidomide + alkylating agent (cyclophosphamide / melphalan) + corticosteroid
- 2nd line: bortezomib + melphalan + prednisolone
Complication Prevention / Management
| Complication | Prevention / management | Indication |
|---|---|---|
| Bone disease | 1st line: zoledronic acid (bisphosphonate) | Indicated for all patients to reduce risk of fractures and bone disease |
| Renal disease | Bortezomib + dexamethasone | Newly diagnosed, myeloma‑induced acute renal disease |
| Infection | Offer:
Consider:
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