Multiple Myeloma (MM)
Background Information
Definition
MM is a haematologic malignancy defined by the presence of abnormal plasma cells within the bone marrow.
Aetiology
Epidemiology: [Ref]
- Median age at onset: 69 y/o
- More common in black individuals (2x compared to white individuals)
- More common in males
Risk factors: [Ref]
- Obesity
- MGUS (nearly all-cases of MM are preceded by MGUS)
Diagnosis
General work-up approach (if MM is clinically suspected):
- Screening tests: laboratory tests, protein studies, imaging
- Definitive test: bone marrow aspiration and biopsy
The full diagnostic criteria for MM are omitted due to their complexity and limited relevance at undergraduate level. Key criteria have been integrated into the sections below.
Clinical Manifestation (End-Organ Damage)
The CRAB criteria represents 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
|
| Bone lesions | Bone lesions in MM include:
|
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 eccmyosies (panda eyes)
- Submandibular gland enlargement
- Unexplained cardiomyopathy
Laboratory Tests
| FBC |
|
| Bone profile |
|
| U&E and metabolic panel |
|
| Peripheral blood smear |
|
Protein Studies
There are 3 main protein studies: [Ref]
| Serum free light chain assay |
|
| Serum protein electrophoresis |
|
| 24-Hour urine electrophoresis |
|
Imaging
Cross-sectional imaging techniques should be used: [Ref]
- Whole-body low-dose CT (preferred due to lower cost)
- Whole-body PET-CT
- Whole-body MRI (highly-sensitive for evaluating the bone marrow)
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
Skeletal survey (conventional radiographs) should NOT be used to assess bone disease. [Ref]
It is less sensitivity as a lytic lesion only becomes visible on a standard X-ray after 30% to 50% of the bone cortex has been eroded
Disclaimer:
- The author acknowledges that it is traditionally taught that whole-body MRI is 1st line imaging for MM.
- NB that the BSH/UKMF guidelines recommends “Cross-sectional imaging, ideally functional (i.e., PET-CT or diffusion weighted whole body MRI), should be used”. There is no clear preference of MRI over CT.
Bone Marrow Analysis
Definitive test: bone marrow aspirate + biopsy [Ref]
- ≥10% of bone marrow plasma cells meets the diagnostic criteria
Management
Definitive Management
Standard 1st line treatment (if transplant eligible) is made up of a 3-phase approach: [Ref]
| Phase 1: induction therapy | Anti-myeloma systemic therapy is 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 | Standard regimen: low-dose continuous lenalidomide (immunomodulatory agent) |
Complication Management
| Complication | Management | Indication |
|---|---|---|
| Bone disease | Bisphosphonates / denosumab | Indicated in all patients to reduce risk of fractures and bone pain |
| Anaemia and neutropaenia | Erythropoietin for anaemia and filgrastim (G-CSF) for neutropaenia | Patients experiencing therapy-related low blood counts |
| Viral infection | Aciclovir / valaciclovir | Mandatory for patients receiving proteasome inhibitors (e.g. bortezomib), anti-CD38, or anti-SLAM7 monoclonal antibodies to prevent shingles/varicella reactivation |
| Bacterial infection | Levofloxacin | Select patients only, such as those with multiple comorbidities |