Focusing on Diagnosis
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A diagnosis of Multiple Myeloma (MM) is based on a number of clinical features and biomarkers.[1] This page will explore the investigative work in more detail.
Diagnostic pathway
Symptoms in MM are often vague and include musculoskeletal pain and tiredness.[2] The presentation of symptoms, the course of the disease and the clinical behaviour vary greatly from patient to patient.[3] Due to this heterogeneous nature it may be challenging for general health practitioners (GPs) to decide on when to refer patients with MM to a haematologist or hospital.[2] As a result, MM patients are more likely than other cancer patients to have three or more GP visits before their referral.[2] The other route of diagnosis is through emergency diagnosis which is usually associated with poorer outcomes.[2]
The MM diagnostic pathway[2][3]
Diagnostic tests[3]
Diagnosis of MM should be based on the following tests:
- Complete blood cell count, differential serum creatinine, creatinine clearance and calcium level
- Bone marrow aspirate or biopsy: number and characteristics of plasma cells, cytogenetic/FISH analysis
- Immunofixation: heavy- and light-chain characterisation
- Nephelometry:
- Immunoglobulin quantification (IgG, IgA and IgM)
- Serum FLC assay
- Serum and/or urine protein electrophoresis: M-protein quantification
- MRI (whole body or spine and pelvis): evaluation of focal bone lesions
- Whole-body low-dose CT: evaluation of lytic bone lesions
- PET-CT: evaluation of bone lesions
CT, computed tomography; FISH, fluorescence in situ hybridisation; FLC, free light chain; Ig, immunoglobulin; M, monoclonal; MRI, magnetic resonance imaging; PET-CT, positron-emission tomography with computed tomography
Signs and symptoms
Disease presentation and progression can vary significantly from patient to patient.[1][3] These symptoms are referred to as CRAB (Calcium (elevated), Renal impairment, Anaemia and Bone disease).
Patients most commonly present with:[4]
C
Calcium levels elevated (hypercalcaemia)
R
Renal impairment
A
Anaemia
B
Bone disease
Less common symptoms
Less common symptoms (occurring in 5% of patients) include extramedullary soft-tissue plasmacytomas or spinal cord compression following vertebral fractures.[4] Patients may also present with recurring bacterial infections, with about one-third of patients diagnosed following investigation of elevated erythrocyte sedimentation rate, total protein or immunoglobulins.[4] Patients with increased monoclonal (M) protein can experience headaches, nose bleeds, confusion and blurred vision.[4]
Some patients may consult their GP because of non-specific symptoms such as fatigue or back pain, while others may present at the emergency room with acute symptoms such as a long bone fracture or spinal compression.[4]
Diagnosing Multiple Myeloma
Smouldering MM
The diagnosis of smouldering MM requires the following criteria to be met:[1]
- Serum M-protein of ≥30 g/L or urinary M-protein of ≥500 mg per 24 hours
- 10–60% clonal bone marrow plasma cells
- Absence of any myeloma-defining events or amyloidosis
The role of M-protein
Not all patients with MM have M-protein in their serum or urine.[5] For this reason, the presence of M-protein is not required for a diagnosis of MM; rather, it is used to differentiate between secretory and non-secretory types.[1]
Symptomatic MM
Although each patient may present very differently, the diagnosis of symptomatic MM requires a number of specific criteria.
Patients should have at least 10% clonal bone marrow plasma cells or biopsy-proven bony or extramedullary plasmacytoma, and any one or more myeloma-defining events (CRAB and/or biomarker of malignancy).[1]
CRAB criteria providing evidence of end-organ damage related to the underlying plasma cell disorder:[3]
- Calcium levels elevated
- Renal insufficiency
- Anaemia
- Bone lesions
Any one or more biomarkers of malignancy:[3]
- At least 60% clonal bone marrow plasma cells
- Involved: uninvolved serum free light chain (FLC) ratio ≥100
- At least one focal lesion on magnetic resonance imaging (MRI)
(each at least 5 mm in size)
Find out more
About Multiple Myeloma
Even with significant advances in treatment, MM remains a challenging disease. Find out more about the evolution of MM.
Response measurements
The right treatment plan can improve a patient treatment response. Find out how treatment response is measured and what strides are being taken to optimise it.
