Tests

Step 2: Tests you really need

Myeloma can have different features in each patient. It is important to understand your disease and to know which tests are best for monitoring your myeloma.

Understanding testing

No single test tells the whole story about a patient’s status. Used together, test results give a more complete picture, and results best reflect a patient's status when looked at over time as a trend or pattern. Test results are the most important tools you and your physician have to:

  • Diagnose active myeloma versus the earlier disease conditions (MGUS or “smoldering” myeloma)
  • Assess the stage of myeloma and good or poor risk features
  • Determine if you need to begin treatment
  • Determine the best treatment option(s)
  • Evaluate your response to treatment
  • Monitor the course of your myeloma over time.

Types of tests

Tests for myeloma fall into several groups:

  • Laboratory tests (blood and urine)
  • Imaging studies (skeleton)
  • Pathology studies (biopsies)
  • Genetic studies (done on biopsy specimens)
  • There are also tests used in special circumstances (amyloidosis, neuropathy, kidney or infectious complications)

Blood tests

Blood tests are done routinely at the time of diagnosis and throughout the disease course to assess response to treatment and side effects, and to monitor for possible relapse.

  • Complete blood count (CBC) assesses the presence or absence of anemia (low red blood cell count), low white blood cell count, and low platelet count.
  • Chemistry/Metabolic Panel is particularly important for assessing kidney function (creatinine and BUN), albumin, calcium level, and LDH.
  • Serum Protein Electrophoresis (SPEP) assesses the amount of abnormal (monoclonal) protein, but does not identify its type.
  • Immunofixation electrophoresis demonstrates the type of myeloma protein; i.e., heavy chain (G, A, D, or E); or light chain (kappa or lambda), but does not quantify it.
  • Freelite® test (serum free light chain assay) measures the number of free kappa or free lambda light chains (fragments of the monoclonal protein) if it is not possible to quantify heavy chains with SPEP or light chains with urine protein electrophoresis (UPEP). Some patients' myeloma cells secrete very little or no monoclonal protein that can be detected with SPEP or UPEP; the majority of these patients can be tested adequately with the Freelite® test.

Urine tests

Urine protein electrophoresis (UPEP)

UPEP shows the amount of monoclonal protein in the urine. Only monoclonal light chains, not heavy chains, are found in urine. Approximately 30% of patients have light chain protein in their urine as well as heavy and light chains in the blood. Approximately 10% of patients have myeloma cells that produce only light chains and no heavy chains.

Urine immunofixation

This test identifies the type of abnormal myeloma protein in the urine (kappa or lambda light chains).

Biopsies

Bone marrow biopsies

Bone marrow aspirate and biopsy are performed routinely to diagnose myeloma, and are also used for periodic monitoring during the course of treatment. Bone marrow biopsies provide information about the amount of disease, the type of disease, its aggressiveness, and molecular/genetic abnormalities that help to predict the disease course. They are necessary because they provide the only direct access to tumor cells for examination by a pathologist. However, because myeloma is patchy and is not distributed evenly throughout the bone marrow, such biopsies do not always present an accurate sample of what is occurring elsewhere in the marrow.

Other tissue biopsies

Other tissue biopsies are performed less frequently to determine if myeloma is present outside the bone marrow. A biopsy may also be performed in early-stage disease on a solitary plasmacytoma.

The Freelite® test

Serum free light chain assay

The importance of the Freelite® test (also known as serum free light chain assay) has grown over time as we have come to know more about the biology of myeloma.

What is Freelite?

An intact (whole) immunoglobulin (the medical term for antibody, abbreviated “Ig”) is made up of two "heavy chains" (which can be of the IgG, IgA, IgD, IgE, or IgM type) and two "light chains," (either kappa or lambda) with the light chains bound to the ends of the heavy chains. The plasma cells produce more light chains than heavy chains, and the excess light chains circulate freely in the blood (called “free” light chains). 

Uses of the Freelite Test

The Freelite test is one way of measuring how much abnormal immunoglobulin protein the myeloma cells are secreting. By quantifying the output of myeloma cells, doctors can infer how extensive and how active the myeloma is at diagnosis and throughout the treatment course.

The Freelite assay is used for patients whose plasma cells only secrete light chains, for those whose cells secrete both heavy and light chains, and for those whose cells secrete very low levels of both heavy and light chains.

The Freelite test is also used to diagnose and monitor the status of people who have MGUS (monoclonal gammopathy of undetermined significance), and help determine the risk of MGUS patients developing active myeloma.

The Freelite test is used to help determine if a person has a high risk of progressing to symptomatic myeloma within 18 months to 2 years. Such patients should be treated if the ratio of light chains that are being secreted by the myeloma cells (the “involved” light chains) to light chains that are normal (the “uninvolved” light chains) is greater than or equal to 100.

Imaging

X-Rays

X-Rays are done to search for myeloma-caused bone damage. A full skeletal x-ray survey can demonstrate loss or thinning of bone (osteoporosis or osteopenia), holes in bone (lytic lesions), and/or fractures. X-rays are simple to do and are inexpensive. Their limitations are that 30% or more of the bone must be missing before x-ray can reveal the damage, and that damage to a bone shows up permanently on x-ray, even if there is no longer any active myeloma. 

MRI (Magnetic Resonance Imaging)

Magnetic Resonance Imaging (MRI) is a non-invasive way to produce a detailed two- or three-dimensional image of structures inside the body. It is the preferred study for imaging the spine, pelvis, and sternum, and for detecting focal lesions in patients with smoldering myeloma. It is useful for imaging plasmacytomas and compression of the spinal cord. MRI is useful for rapidly detecting new disease, but there is at least a 9-month lag before an MRI will look normal after an area of myeloma has been successfully treated and is no longer active. MRI may pose a problem for patients who have metal implants. Patients with myeloma kidney involvement should discuss the use of contrast gadolinium with their oncologists prior to scheduling an MRI.

CT or CAT Scan (Computerized Axial Tomography)

Computerized Axial Tomography (CT or CAT) scan uses x-ray technology to create a three-dimensional digital image of the body that is more precise than x-ray and can provide clear, detailed images of bone. Downsides include expense, the increased level of radiation as compared to x-ray, and the possible need to use contrast agents that can pose problems for myeloma patients with kidney dysfunction

PET Scan (Positron-Emission Tomography)

(Positron-Emission Tomography) PET scan requires that a patient be injected with fluoro-deoxyglucose (FDG), a sugar-fluorine compound that is taken up by the body's actively multiplying cells. The areas with the highest concentrations of fluorine "glow" can indicate cancer cells. PET scan covers the whole body, is very sensitive in detecting potential tumor activity, and is the only "real-time" imaging study. It is a valuable tool for patients whose myeloma is difficult to assess, and for situations where x-ray, MRI, and CT do not provide enough information about potential new disease. 

PET/CT

PET/CT combines PET and CT scans in one imaging study, providing information both about past damage and current cancer activity, thus enabling the doctor to study changes over time. It is a highly accurate study, but is expensive and time-consuming. 

Staging

In 2005, the IMF sponsored the development of the International Staging System (ISS), previously called the International Prognostic Index (IPI). The ISS was developed through a collaborative research initiative conducted by nearly 20 myeloma institutions around the world to provide precise, individualized treatment selection. It became an alternative to the Durie-Salmon Staging System used in myeloma for more than 25 years. The ISS is based on the statistical power and wide availability of two simple blood tests: serum ß2microglobulin (Sß2M) and serum albumin. 

In 2015, the International Myeloma Working Group (IMWG) published its Revised International Staging System (R-ISS), which combines the ISS with chromosomal abnormalities detected by interphase fluorescence in situ hybridization (FISH) and serum lactate dehydrogenase (LDH). Clinical data from 4,445 patients with newly diagnosed myeloma in 11 international clinical trials were analyzed to create this updated powerful prognostic staging system.  

REVISED INTERNATIONAL STAGING SYSTEM (R-ISS) FOR MYELOMA

Stage Criteria
I

Serum β2 microglobulin < 3.5 mg/l
Serum albumin ≥ 3.5 g/dl
Standard-risk chromosomal abnormalities (CA)
Normal LDH

II Not R-ISS stage I or III
III

Serum β2 microglobulin ≥ 5.5 mg/L and either
High-risk CA by FISH
OR
High LDH

Genetic testing

Genetic testing is performed on a patient's bone marrow biopsy specimen at the time of diagnosis to help predict the behavior of the myeloma and its response to various treatment strategies. 

Conventional Metaphase Cytogenetics (karyotyping)

For this test, the bone marrow biopsy specimen is placed into a special dish and allowed to grow in the laboratory. Cells from the growing sample are stained, then photographed to provide a karyotype, which shows the arrangement of the chromosomes. Certain abnormalities can be identified through the number or arrangement of the chromosomes. This test is particularly valuable for identifying higher-than-average-risk myeloma in patients with fewer than two copies of each chromosome (hypodiploidy) and in those with deletion of chromosome 13 during cell division.

Fluorescence In-Situ Hybridization (FISH)

This test provides a way to visualize and map the genetic material in an individual's cells, including specific genes or portions of genes, which is important for understanding a variety of chromosomal abnormalities and other genetic mutations. Unlike most other techniques used to study chromosomes, FISH does not have to be performed on cells that are actively dividing. FISH is useful for defining high-risk myeloma in patients with certain chromosomal translocations and/or in those who have a deletion of the short arm of chromosome 17.