Myeloma Diagnosis and Staging

The myeloma diagnosis process may require a variety of tests so the care team can accurately pinpoint the disease type and stage. The care team will then use that information to develop a personalized myeloma treatment plan.

Diagnostic Tests for Multiple Myeloma

Myeloma is diagnosed using various tests, including those listed below.

Lab Tests for Multiple Myeloma

The care team is likely to order lab tests early in the myeloma diagnosis process. Blood tests are important in helping the care team identify whether the patient has too much of a protein called immunoglobulin, and which protein types are present. Blood tests also provide information about red and white blood cells counts, how much calcium is in the patient's blood and whether his or her kidneys are functioning properly.

Urine tests are another helpful tool in assessing the amount of protein in the patient's body. In some cases, the care team may ask the patient to provide urine samples over a period of 24 hours during a test called urine protein electrophoresis (UPEP) and urine immunofixation

Bone Marrow Biopsy for Myeloma

The care team will typically need to perform a biopsy before confirming a myeloma diagnosis. To do this, the provider will extract bone marrow from the patient's bone using a needle. This is called bone marrow aspiration. 

The extracted bone marrow is then examined by a pathologist, who will determine whether and how many myeloma cells are present.

Imaging Tests for Myeloma

During the myeloma diagnosis process, the care team may order imaging tests. These studies may also be performed throughout treatment to monitor the disease and evaluate whether treatment is working.

Magnetic resonance imaging (MRI): The MRI test may allow the care team to evaluate whether myeloma cells have replaced healthy bone marrow. This test may also be able to detect bone fractures or tumors.

Computed tomography (CT) scan: The CT scan provides images that allow the care team to evaluate the health of soft tissues and detect the presence of any tumors or bone damage (such as lytic lesions).

Positron emission tomography (PET) scan: During this test, the patient receives a small amount of radioactive sugar. The body parts that absorb the substance are evaluated more closely for potential cancer. Because cancer cells are more active than healthy cells, they react more strongly to the sugar than healthy cells do.

Other Myeloma Tests

Biomarker testing may be performed for some myeloma patients during the diagnosis process. This may also be referred to as molecular testing. During this process, the care team evaluates genetic changes in the patient's cells or tissues to help diagnose the myeloma type and help guide treatment decisions.

Myeloma diagnosis for older patients may also include an extra layer of assessment to determine how well they can tolerate treatments like chemotherapy.

CRAB Criteria in Multiple Myeloma

To diagnose multiple myeloma, there must be evidence of end-organ damage. This is evaluated using what is known as CRAB criteria. Symptomatic or active multiple myeloma is diagnosed when the percentage of plasma cells in the bone marrow exceeds 10% and a patient has one or more of the symptoms listed below.

C stands for high levels of calcium in the blood: Blood calcium above 2.75 mmol/L (> 11 mg/dL). High calcium may damage various organs, including the kidneys, heart and brain.

R is for renal (kidney) dysfunction: Too much of the waste product creatinine in the blood suggests kidney impairment. The concerning level is 177 μmol/L (> 2 mg/dL).

A stands for anemia: Anemia means the blood lacks enough red blood cells to supply oxygen to organs. The telling level is a hemoglobin level of < 10 g/dL.

B is for bone damage: One or more signs of bone damage, such as lesions found via imaging, fractures or weakening, is present.

Myeloma-Defining Events

Other factors, such as myeloma-defining events (MDEs), also help aid in the diagnosis of multiple myeloma. For a diagnosis, one or more of these MDEs may be present:

• At least 60 percent clonal plasma cells upon bone marrow examination
• Serum involved (the one above the normal reference range) to uninvolved (the one typically at or below the normal reference range) free light chain ratio of 100 or greater
• More than one focal lesion found using magnetic resonance imaging (MRI) that is at least 5 mm or greater in size

Multiple Myeloma Screening

If the patient is part of a high-risk group, the care team may recommend myeloma screening.

Screening may be recommended to detect early-stage multiple myeloma in two high-risk populations:

• Black people over the age of 50 with one or more relatives with the disease
• People of other ethnicities over the age of 50 who have two or more relatives with myeloma

Multiple Myeloma Stages

Following diagnosis, the care team will assign a myeloma stage to help guide treatment decisions. During the staging process, the care team will review the outcomes of diagnostic tests to evaluate the patient’s protein levels and other features.

Multiple myeloma is staged based on multiple factors, according to the Revised International Staging System (R-ISS).

Stage 1 Multiple Myeloma

The R-ISS features that must be present to classify a patient with stage 1 myeloma are:

• Beta-2 microglobulin below 3.5 mg/L
• Serum albumin level of 3.5 g/dL or greater
• Cytogenetics (specific gene abnormalities) are not considered high risk 
• Lactate dehydrogenase at normal levels

Stage 2 Multiple Myeloma

According to the R-ISS, the following feature defines stage 2 myeloma:

• The patient’s characteristics don’t fall into stage 1 or stage 3

Stage 3 Multiple Myeloma

Stage 3 is the highest myeloma stage, and there is no stage 4 of this cancer type. The R-ISS defines stage 3 multiple myeloma as meeting the following criteria:

• Beta-2 microglobulin is 5.5 mg/L or greater
• Cytogenetics are considered high-risk, and/or high lactate dehydrogenase levels are observed

Stage 0 Multiple Myeloma

Only active myeloma is assigned using stages 1 through 3. If a patient has smoldering myeloma (also called asymptomatic myeloma), the care team may describe it as being stage 0 multiple myeloma. This myeloma type has the following features:

• Normal blood counts, calcium levels and kidney function
• No noticeable damage to organs or bones
• Serum monoclonal protein of 3 g/dL or higher and/or 10% to 60% of all cells in bone marrow are plasma cells