Patient journey to a diagnosis of multiple myeloma

A diagnosis of multiple myeloma 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 multiple myeloma 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 can prove challenging for general health practitioners (GPs) to decide on when to refer patients with multiple myeloma to a haematologist or hospital.2 As a result, multiple myeloma patients are more likely than other cancer patients to have three or more GP visits before their referral. The other route of diagnosis is through emergency diagnosis which is usually associated with poorer outcomes.2,3

The multiple myeloma diagnostic pathway2,3

The multiple myeloma diagnostic pathway

  • 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

Patients most commonly present with:4

Signs and symptoms


Signs and symptoms

Renal impairment

Signs and symptoms


Signs and symptoms

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

Symptom presentation
Some patients may consult their general practitioner 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

The variations in presentation and routes to diagnosis can all impact the time it takes for a patient to receive their diagnosis4

Diagnosing multiple myeloma

Criteria for diagnosis

Although each patient may present very differently, the diagnosis of symptomatic multiple myeloma requires a number of specific criteria to be met.1

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:1

CRAB features that provide 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)

      Smouldering myeloma vs symptomatic myeloma

      Smouldering myeloma can be distinguished from symptomatic myeloma if a patient has a serum M-protein of ≥30 g/L or urinary monoclonal protein of ≥500 mg per 24 hours, and/or 10–60% clonal bone marrow plasma cells, and the absence of any myeloma-defining events or amyloidosis.1

      Testing for monoclonal protein

      Not all patients with multiple myeloma have M protein in their serum or urine.5 For this reason, the presence of M protein is not required for a diagnosis of multiple myeloma, rather it is used to differentiate between secretory and non-secretory types.1

      Find out more

      Understanding Multiple Myeloma

      Even with significant advances in treatment, myeloma remains a challenging disease. Find out more about this type of cancer and its pathophysiology.
      Learn more


      1. Rajkumar S et al. Lancet Oncol  2014; 15(12):e538–e548.
      2. Howell D et al. Br J Haematol  2017;  177(1):67–71.
      3. Moreau P et al. Ann Oncol  2017; 28(Suppl_4):iv52–iv61.
      4. Smith D, Yong K. BMJ  2013; 346:f3863.
      5. International Myeloma Working Group. Br J Haematol  2003; 121(5):749–757.

      ITEM CODE: CP-171721 | DATE OF PREPARATION: September 2020