There are many factors your doctor will rely on to form an accurate multiple myeloma diagnosis — overall health, symptoms and diagnostic tests of blood, urine and bone marrow play an important role. Being diagnosed with a disease like multiple myeloma can feel overwhelming. These are some of the steps you can take to begin management of your disease.
Multiple Myeloma Classifications
Knowing the classification of your disease is very important in deciding when it is appropriate to begin treatment. Classification also plays an important role in determining the stage of multiple myeloma.
MGUS is a plasma cell neoplasm diagnosed when a small amount of M protein is detected in the blood, but no other criteria for a solitary plasmacytoma or multiple myeloma diagnosis (such as a tumor, multiple lesions or symptoms) are present. MGUS occurs in about 1% of the general population.
MGUS usually does not cause any problems or require treatment, but in rare cases (1%-2%), it can develop into multiple myeloma. People living with MGUS receive regular checkups to ensure that it does not progress. A single group of malignant myeloma cells (rather than multiple lesions, as in multiple myeloma) is called a “solitary plasmacytoma.” This mass of cells can grow inside or outside of bone. An “extramedullary plasmacytoma” is one that grows outside the bone, while an “isolated plasmacytoma of the bone” is one that grows within the bone. Isolated plasmacytoma of the bone can affect any bone, but tends to occur most frequently in the bones along the spinal column.
Solitary plasmacytoma within the bone is normally diagnosed by a biopsy that reveals abnormal plasma cells. With a solitary plasmacytoma, bone imaging (X-rays, positron-emission tomography [PET] scan or magnetic resonance imaging [MRI]) detects only a single lesion. Blood tests show no anemia or high calcium levels, and kidney function is normal. Solitary plasmacytoma is rare, making up only 5% of plasma cell disorders. It is commonly treated with radiation therapy and rarely requires surgery. Prognosis with radiation alone is usually excellent, but there is a risk that a solitary plasmacytoma could recur and progress to multiple myeloma. People with a solitary plasmacytoma will have long-term follow-up appointments to ensure they remain in remission. Smoldering multiple myeloma (SMM) is a precancerous form of multiple myeloma that typically accounts for about 15% of newly diagnosed multiple myeloma cases. It is diagnosed when low levels of M protein are found in the blood and a slightly increased number of plasma cells are found in the bone marrow. Many patients with SMM are asymptomatic, but some experience modest symptoms, such as mild anemia or a few small bone lesions.
Many — but not all — patients with SMM progress to multiple myeloma. The risk of progression is about 10% each year for the first 5 years following diagnosis, 3% between years 5 and 10 and about 1% in subsequent years. The commonly accepted approach to SMM used to be “watchful waiting.” Now, however, many studies are showing the benefit of earlier treatment, particularly for people with SMM that has genetic traits that put them at higher risk for disease progression to full-blown multiple myeloma. Early intervention has demonstrated success in preventing multiple myeloma development. Further studies are under way, and a main initiative of the MMRF is to ensure that each individual receives the best treatment available. Multiple myeloma is a type of cancer that affects plasma cells in the blood, causing them to grow and divide. The “multiple” in multiple myeloma indicates that there are multiple tumors in different areas of the bone(s). More than 90% of individuals diagnosed with multiple myeloma have multiple tumors at the time of diagnosis.
Characteristics of multiple myeloma include elevated levels of M protein and plasma cells in the serum and/or urine, a percentage of plasma cells in the bone marrow over 30%, anemia, renal failure, hypercalcemia and osteolytic lesions. When present, symptoms of multiple myeloma may be vague and similar to those of other conditions. Some multiple myeloma symptoms are more common than others, and less common symptoms may be the result of complications that may occur. Management of multiple myeloma includes immediate treatment with myeloma drugs, bisphosphonates for patients with bone loss and options for clinical trials. Depending on the classification of your disease, as well as other factors, you may not have to receive treatment immediately. In some cases, postponing therapy may help avoid unnecessary side effects and the risk of complications associated with chemotherapy, and it may also delay development of resistance to chemotherapy. Even if you don’t receive disease-directed therapy right away, you may still receive supportive care to treat symptoms or complications. Work with your healthcare team to determine the right treatment approach for you.1. Monoclonal gammopathy of undetermined significance (MGUS)
2. Solitary (or isolated) plasmacytoma
3. Smoldering (or asymptomatic) multiple myeloma
4. Multiple myeloma
Diagnostic criteria and tests
Diagnostic testing for multiple myeloma includes a range of blood tests, urine tests and bone or bone marrow tests. Undergoing all of the appropriate multiple myeloma tests is very important, as the results will help your doctor better determine treatment options and a prognosis. Many of these tests are also used to assess the extent of the disease and to plan and monitor treatment.
In addition to diagnostic testing, we strongly endorse genomic sequencing for people with multiple myeloma when possible. Genome sequencing can provide valuable information about your prognosis, your treatment options and how your cancer is changing in response to treatment. The factors that help doctors evaluate and diagnose a disease are known as diagnostic criteria. The diagnostic criteria for multiple myeloma are based on the results of diagnostic tests done on specimens of blood, urine, bone and bone marrow.
Diagnostic criteria are used to determine not only if multiple myeloma is present but also the extent of the disease. They are valuable for both classifying and staging multiple myeloma. The diagnostic criteria for multiple myeloma require confirmation of (a) one major criterion and one minor criterion or (b) three minor criteria in an individual who has signs or symptoms of multiple myeloma. Major criteria: Minor criteria:Diagnostic criteria
Complete blood count
Counts the number of red blood cells, white blood cells and platelets and analyzes the relative proportion of white blood cells compared to the rest of the blood cells. This can help determine how much multiple myeloma is interfering with the normal production of blood cells. Low blood cell levels may signal anemia, increased risk for infection and/or poor clotting.Chemistry profile
This set of tests measures levels of albumin, calcium, L-lactate dehydrogenase [LDH], blood urea nitrogen [BUN], and creatinine in the blood. The results are used to assess how well the kidneys and liver are functioning and can indicate bone status (bone loss due to multiple myeloma) and extent of disease.Beta2-microglobulin (ß<2M) level
Indicates the presence and the extent of multiple myeloma. It is also an indicator of kidney function. Higher ß2M levels can indicate that more extensive disease is present, helping your doctor determine the stage of the disease.Antibody (immunoglobulin, or Ig) levels and antibody type (Ig type G or Ig type A)
Determines levels of IgG or IgA antibodies, overproduced by myeloma cells, in the blood. Higher antibody levels suggest the presence of multiple myeloma.Serum protein electrophoresis
Detects the presence and levels of various proteins, including M protein, in the blood. Higher protein levels indicate more extensive disease and can aid in classification and staging of the disease.Immunofixation electrophoresis (IFE; also called immunoelectrophoresis)
Identifies the type of abnormal antibodies present in the blood (usually type IgG or IgA), and aids in classification of the disease.Serum free light chain assay
Measures antibody light chains made by myeloma cells. Light chains (also called Bence Jones proteins) are classified as either kappa or lambda. Abnormal levels and/or ratios of free light chains suggest the presence of multiple myeloma or a related disease.Urinalysis
This set of tests is used to assess kidney function. It includes chemical analyses (looking for blood, glucose, protein and other substances that might be present in the urine and measuring what amount is present) and sometimes visual examination of the urine through a microscope. Abnormal findings may suggest kidney damage due to multiple myeloma.Urine protein level (performed on a 24-hour specimen of urine)
Measures the presence and level of light chains (Bence Jones proteins) found in the urine. Presence may indicate multiple myeloma, and higher levels indicate more extensive disease.Urine protein electrophoresis
Determines the presence and levels of specific proteins, including M protein and Bence Jones protein, in the urine. The presence of M protein or Bence Jones protein indicates multiple myeloma.Imaging studies
These tests include bone (skeletal) survey, X-ray, MRI, CT and PET. These tests assess changes in the bone structure and determine the number and size of tumors in the bone. Higher levels of bone changes suggest the presence of multiple myeloma.Bone marrow biopsy or aspiration
In a bone marrow biopsy, your doctor will remove a small piece of bone that contains marrow. For a bone marrow aspiration, your doctor will remove a small amount of liquid bone marrow, which contains marrow cells. Both of these samples are usually taken from the pelvic (hip) bone using a large needle.These tests are important for several reasons. First, they can be used to determine the number and percentage of normal and cancerous plasma cells in the bone marrow. Presence of multiple myeloma cells in the bone marrow confirms the diagnosis of multiple myeloma. A higher percentage indicates more extensive disease. Second, the myeloma cells that are collected from your bone marrow can be used to perform genomic sequencing, which is vital in determining your myeloma subtype and may also be useful in determining what your treatment plan should be.
Genome sequencing in multiple myeloma
From a genetic perspective, not all multiple myeloma is the same. In fact, there are at least 12 distinct subtypes of multiple myeloma. Since each has different genetic mutations and expression levels of various genes, researchers think that each subtype of multiple myeloma might respond differently to different treatments.What is genome sequencing?
Multiple myeloma genome sequencing is the process of examining your tumor DNA. The DNA in cancer cells is made up of the same molecular “stuff” as the DNA in normal cells, but it has been rearranged. When these genetic alterations (called “mutations”) happen, the proteins produced in those cells can no longer do the job they’re supposed to do and instead start doing what the cancerous DNA wants them to do.Sequencing DNA allows a doctor to understand how your tumor is working — how it grows, how it is trying to avoid detection by the immune system, and even how it might respond to specific therapies.
What are the benefits of having your genome sequenced?
Genome sequencing can give you information about your prognosis, your treatment options and how your cancer is changing in response to treatment. For example, the MMRF is sponsoring the MyDRUG trial, the first platform trial in myeloma, that enrolls patients with high-risk disease into different treatment arms based on their genomic alterations. All enrolled patients receive a standard of care regimen (Ninlaro, Pomalyst and dexamethasone) plus a therapy that is targeted against their specific genomic alteration. If the patient does not have a targetable alteration, they receive a four-drug therapy combination that includes an immunotherapy agent. All of the targeted therapies in the MyDRUG trial are either approved for use or are in clinical trials in other types of cancer and are only available to myeloma patients through MyDRUG.Genome Tests Table
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