How is multiple myeloma suspected and diagnosed?

From the Guidelines

Multiple myeloma is suspected and diagnosed through a combination of clinical presentation, laboratory tests, and imaging studies, with definitive diagnosis requiring bone marrow biopsy and aspiration, as well as the presence of end-organ damage, such as hypercalcaemia, renal insufficiency, anaemia, or bone lesions, as outlined in the CRAB criteria 1. The diagnosis of multiple myeloma typically begins with blood tests, including:

• Complete blood count to check for anemia
• Serum protein electrophoresis to detect abnormal proteins (M-proteins) produced by cancer cells
• Measurement of free light chains
• Calcium levels and kidney function tests, as elevated calcium and renal impairment are common in multiple myeloma Urine tests are also performed to examine for Bence Jones proteins (light chains). Imaging studies, such as:
• X-rays
• MRI
• CT
• PET scans help identify bone lesions characteristic of the disease. Bone marrow biopsy and aspiration are essential for definitive diagnosis, where samples are examined for the presence of abnormal plasma cells (typically 10% or more indicates myeloma) 1. The International Myeloma Working Group has established criteria for the diagnosis of plasma cell proliferative disorders, which include the presence of monoclonal immunoglobulins, bone destruction, suppression of bone marrow function, and renal damage 1. The most recent and highest quality study, published in 2017, recommends the use of serum-free light-chain measurement, as well as imaging techniques, such as MRI and PET-CT, in the assessment of patients with multiple myeloma 1. Key points to consider in the diagnosis of multiple myeloma include:
• Clinical presentation, such as bone pain, fatigue, recurrent infections, or kidney problems
• Laboratory tests, including complete blood count, serum protein electrophoresis, and measurement of free light chains
• Imaging studies, such as X-rays, MRI, CT, or PET scans
• Bone marrow biopsy and aspiration
• Presence of end-organ damage, such as hypercalcaemia, renal insufficiency, anaemia, or bone lesions, as outlined in the CRAB criteria.

From the Research

Diagnosis of Multiple Myeloma

The diagnosis of multiple myeloma requires a combination of clinical evaluation, laboratory tests, and imaging studies. Some key points to consider include:

• Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging 2.
• The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) attributable to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L and urine monoclonal protein is ≥200 mg/24 h), or >1 focal lesion on magnetic resonance imaging 3.
• Accurate diagnosis is generally based on several factors, including physical evaluation, patient history, symptoms, and diagnostic testing results. The standards for initial diagnostic tests are determined by blood and urine tests as well as a bone marrow biopsy and skeletal imaging, such as X-rays, CT scans, and MRI scans 4.

Diagnostic Tests

Some common diagnostic tests used to diagnose multiple myeloma include:

• Complete blood count with differential
• Serum chemistries
• Creatinine, lactate dehydrogenase, and beta2-microglobulin tests
• Immunoglobulin studies
• Skeletal survey
• Bone marrow evaluation 5
• Serum free light chain measurements and serum and urine electrophoresis 6

Staging and Risk Stratification

The Revised International Staging System combines data from the serum biomarkers β2 microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features found on fluorescence in situ hybridization-t(4;14), del(17p), and t(14;16)-to assess estimated progression-free survival and overall survival 2.

• The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, del 1p, or p53 mutation is considered high-risk multiple myeloma 3.