Tests for Diagnosis and Monitoring

The progression of myeloma varies greatly from person to person. Accurate diagnosis and risk stratification are essential in choosing the best available therapy at each phase of the disease. The most up-to-date International Myeloma Working Group (IMWG) recommendations will assist the advanced practitioner in effective diagnosis, treatment, and monitoring of multiple myeloma patients.

Tests are an integral tool practitioners can use in the diagnosis, treatment and monitoring of myeloma patients. Useful tests may include:

Types of Tests

Laboratory analysis of blood and urine:

Complete blood count (CBC) and metabolic panel, including

Calcium	Used to assess the “C” in the CRAB criteria – elevated calcium in the blood. A high blood calcium level can also damage the kidneys.
Uric acid	May be elevated as a complication of myeloma and can indicate kidney impairment
Creatinine	Used to assess the “R” in the CRAB criteria, Renal (kidney) function, by measuring how well the kidneys are functioning. Used in conjunction with creatinine to screen for and detect kidney damage.
estimated glomerular filtration rate (eGFR)	Used in conjunction with creatinine to screen for and detect kidney damage
Albumin (ALB)	The most abundant protein in the blood. Indicates the amount and activity of the underlying myeloma. It is included in the revised International Staging System (R-ISS) to help understand the potential for the spread and aggressiveness of newly diagnosed myeloma.
Beta-2 microglobulin (β2m	Indicates the amount and activity of the underlying myeloma. It is included in the revised International Staging System (R-ISS) to help understand the potential for the spread and aggressiveness of newly diagnosed myeloma. It can also be used to evaluate disease activity and to monitor response to treatment.
Lactate dehydrogenase (LDH)	It is a sign of aggressive disease and is included in the R-ISS to help determine prognosis. LDH rises when myeloma is actively growing.
C-reactive protein (CRP)	Used in assessing heart disease and autoimmune diseases. It is an indicator of inflammation and increased levels indicate active myeloma.

M-Proteins

Serum Protein Electrophoresis (SPEP)	One of the most important tests used to diagnose and assess the status of myeloma. It measures the amount of M-protein that is made by myeloma cells.
Urine protein electrophoresis (UPEP)	Tests for light chain protein in the urine. It is performed on a 24-hour urine collection.
Immunofixation (IFE)	Usually done following an abnormal result on SPEP. It identifies the type of M-protein present but does not measure the amount. It is performed on a 24-hour urine collection.
Quantitative immunoglobulin (IgG, IgA, IgM, etc.)	Measures the total amount of each primary immunoglobulin class. If an increase in one of the antibody isotypes is found, further testing with electrophoresis is required to determine if the elevation is caused by the presence of monoclonal immunoglobulin protein.
Serum Free Light Chain (Freelite®) assay	Often used with SPEP to monitor patients after treatment. It is also used to diagnosis and monitor patients who have monoclonal gammopathy of undetermined significance (MGUS) to assess risk of developing active myeloma and patients who have smoldering multiple myeloma (SMM).
Hevylite® (serum heavy + light chain isotype assay)	Measures intact immunoglobulins and is used for previously diagnosed myeloma in conjunction with other clinical and laboratory findings. When this assessment reveals that normal immunoglobulin levels are suppressed, it can be an early indicator of myeloma relapse. When a patient is in complete remission (CR), this test can detect extremely low levels of M-protein, indicating the presence of “minimal residual disease” (MRD).

Radiologic imaging studies to assess the skeleton:

Skeletal survey	Used to detect lytic bone lesions and bone fractures. Also helps with staging of multiple myeloma, particularly for patients unable to access more advanced methods
Bone density test	Used to detect osteopenia and osteoporosis
Whole body low dose computed tomography (WBLD-CT)	Used to detect lytic bone lesions and bone fractures as well as in staging of multiple myeloma
Magnetic resonance Imaging (MRI)	Used when vertebral compression fracture or spinal cord compression is suspected. It can detect edema and fluid surrounding active vertebral bone disease and marrow and soft tissue involvement
CT or positron-emission tomography (PET)	Used to assess presence of lytic bone lesions and occult plasmacytomas. It can also help after therapy to rule out residual focal lesions

Genetic testing conducted by bone marrow aspiration and biopsy:

Cytogenetics (karyotyping)	Assesses the chromosomes in dividing cells. It is routinely performed on the bone marrow of newly diagnosed myeloma patients and is sometimes repeated after treatment see if the therapy has eliminated all the cells with chromosomal abnormalities. It may also be performed at relapse, to help determine if it is time to resume therapy, and if so, if one therapy might be preferable to another.
Fluorescence in situ hybridization (FISH)	Used to assess genetic risk based on chromosomal abnormalities and is complementary to karyotyping. It assesses the chromosomes of all myeloma cells in a bone marrow sample and allows detection of changes whether myeloma cells are growing or not.
Gene expression profiling (GEP)	Used to identify the dominant clone at any time in a patient’s disease course and classify myeloma into different molecular subgroups. It can also identify the gene expression profile of patients with high-risk myeloma.
Plasma Cell Labeling Index (PCLI)	Used to measure plasma cell proliferative activity and is an important prognostic factor in newly diagnosed multiple myeloma.