Diagnosis

Multiple myeloma can be difficult to diagnose. To form an accurate diagnosis, your doctor will rely on a number of factors, including physical evaluation, symptoms, medical history, and the results of many different diagnostic tests.

The initial evaluation to help confirm a diagnosis of multiple myeloma includes blood and urine tests as well as a bone marrow biopsy. Other tests include X-rays, magnetic resonance imaging (MRI), computed tomography (CT) scans, and positron-emission tomography (PET) scans. Another type of testing known as genome sequencing can provide additional information about the genetic mutations specific to your cancer.

It is very important for you to undergo all of the appropriate tests, as the results will help your doctor better determine treatment options and prognosis. Many of these tests are also used to assess the extent of disease and to plan and monitor treatment.

Being diagnosed with a disease like multiple myeloma can feel overwhelming. That’s why we’ve put together a list of steps to take after a multiple myeloma diagnosis to help you move forward toward getting the care you need.

Learn more about multiple myeloma diagnosis:


 

Now what? Steps to take after a multiple myeloma diagnosis

When you’re diagnosed with a condition like multiple myeloma, it’s important that you be an advocate for your care. Here are some things you can do to help ensure the best possible outcome for you:

1. Find the right treatment center and the right doctor

For diseases that are rare or particularly complicated, such as multiple myeloma, specialized medical understanding is especially important. When considering potential doctors, don’t be afraid to ask them about their experience treating multiple myeloma. Ideally, a hematologist who focuses on multiple myeloma will be aware of the latest research and up-and-coming treatment options. If seeing a hematologist is not possible, you can be treated by another specialist, such as a medical oncologist, who may consult with a hematologist about your care.

Often, specialists work out of specialized cancer treatment centers. Treatment centers that frequently see patients with multiple myeloma have been shown to produce better outcomes than centers that see fewer multiple myeloma patients.

While you may not live close enough for a specialist at a cancer center to be your only source of treatment, consulting a specialist at important times and obtaining specific types of care at a specialized center may help you get the best care possible.

To start your search, you can ask your primary care doctor to recommend a multiple myeloma specialist. Your insurance provider can also supply a list of in-network specialists and their affiliated treatment centers. Additionally, the Multiple Myeloma Research Foundation (MMRF) has an online tool to help patients find a treatment center, and the American Society of Hematology has a search page to “Find a Hematologist.”

The MMRF also strongly encourages everyone diagnosed with multiple myeloma to get a second opinion from a multiple myeloma specialist at the start of treatment and when making changes to your treatment plan—even if the doctor you have been working with is a specialist.

2. Get the right diagnostic tests, and have your genome sequenced

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, the MMRF strongly endorses genome sequencing for people with multiple myeloma. Genome sequencing can provide valuable information about your prognosis, your treatment options, and how your cancer is changing in response to treatment. Having your genome sequenced may also help bring researchers closer to discovering a cure for multiple myeloma.

3. Work with your doctor to determine the right treatment plan, including any clinical trials

There is no one standard multiple myeloma treatment plan. The right treatment plan for you will be based on a number of factors, including:

  • Age and general health
  • Results of laboratory and cytogenetic (genomic) tests
  • Symptoms and disease complications
  • Prior multiple myeloma treatment
  • Your lifestyle, goals, views on quality of life, and personal preferences

In addition to the FDA-approved treatment options available for multiple myeloma, there are also many clinical trials under way. Patients who enroll in clinical trials have the opportunity to be among the first to receive the newest drugs or drug combinations in development and to receive close monitoring. Be sure to talk with your doctor about whether a clinical trial is a good option for you.

4. Share your data with communities and registries to help advance multiple myeloma research

Finding a cure depends on everyone in the multiple myeloma community—doctors, researchers, the pharmaceutical industry, and patients like you. That’s why the MMRF strongly advocates patients sharing their health and treatment information: the more data collected from more patients, the closer we get to better, more targeted treatments. 

Sharing your data can help you understand your cancer in the context of other patients. Our hope for the future is that as patients have their genomes sequenced and learn which, if any, mutations they have, they can connect with other patients like them, engage with researchers who specialize in that particular area of genomics, and sign up for clinical trials that might be right for them.

Resources for newly diagnosed patients:
Finding a treatment center
Support groups



Diagnostic criteria

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:

  • Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
  • >30% plasma cells in a bone marrow sample
  • Elevated levels of M protein in the blood or urine

Minor criteria:

  • 10% to 30% plasma cells in a bone marrow sample
  • Minor elevations in the level of M protein in the blood or urine
  • Osteolytic lesions (as demonstrated on imaging studies)
  • Low levels of antibodies (not produced by the cancer cells) in the blood


Types of antibodies in multiple myeloma

In a healthy person, normal plasma cells produce disease-fighting antibodies (also called “immunoglobulins”). Different plasma cells produce specific antibodies. Each antibody is made up of four protein chains: two long chains (called heavy chains) and two shorter chains (called light chains). Antibodies are classified into one of five classes according to their heavy chain: gamma (IgG), alpha (IgA), mu (IgM), epsilon (IgE), or delta (IgD).

In a person with multiple myeloma, certain plasma cells are converted into multiple myeloma cells. These multiple myeloma cells then cease to produce whichever antibody they once produced (IgG, IgA, etc) and instead start over producing a nonfunctional version of that antibody. The nonfunctional antibody is known as an M protein.

Doctors measure these M proteins with a laboratory technique called protein electrophoresis, which can be performed on blood serum or urine samples. IgG accounts for about 60% to 70% of all multiple myeloma cases, and IgA accounts for about 20% of cases. Discovering which class of antibody has been replaced with M protein will be part of your multiple myeloma diagnosis and will help your healthcare team determine the best approach to your treatment.



Diagnostic tests

The various types of tests and procedures used to diagnose multiple myeloma include:

Blood tests

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.

Freelite 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.

Urine tests

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 how much 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.

Bone/bone marrow tests 

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 can 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.

Cytogenetic analysis (also known as karyotyping and fluorescence in situ hybridization [FISH])

Assesses the number and appearance of chromosomes in multiple myeloma cells in order to identify DNA alterations. Certain DNA alterations may indicate how aggressive the disease is.



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. Knowing that information may be intimidating, but it may also help determine the best treatment available for you. For example, if genome sequencing reveals that a patient has a translocation called t(4;14)—an aggressive form of multiple myeloma with a historically poor prognosis—doctors may decide to try treatment with Velcade (bortezomib), a drug that specifically targets this translocation and has proven to improve outcomes for patients with this mutation.

Having your genome sequenced can also be quite helpful to future multiple myeloma patients. As more patients undergo genome sequencing and more data are collected, more is known about multiple myeloma. This helps advance multiple myeloma treatments and brings researchers closer to discovering a cure.