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Multiple Myeloma

A Roadmap for Multiple Myeloma: Understanding Important Biomarkers

May 2019 Volume 5 – Biomarkers & Molecular Testing
Annie Lattanzio-Hale, MSN, RN, OCN
Ann B. Barshinger Cancer Institute,
Lancaster, PA

Multiple myeloma: say that three times fast. A diagnosis of multiple myeloma often invokes confusion and fear. You may feel as though you were plucked from normal life and inserted into a maelstrom of testing and conversation about treatment and prognosis. Acronyms and abbreviations, not to mention an alphabet soup of terms, start to sound like a foreign language. It can quickly become an overwhelming task to make sense of things and understand what lies ahead.

Fortunately, multiple myeloma is a type of cancer for which outcomes have improved significantly in recent years as new treatments have been developed and proved effective. Many people with multiple myeloma can live for years with the disease, which commonly resembles a chronic condition. That being said, there are many variations within the disease and related to each person that impact the journey.

How Did This Happen?

Cells that make up the immune system have the ability to become either lymphoid cells or myeloid cells as they mature. Lymphoid cells are the captains of the immune system and develop into either T lymphocytes or B lymphocytes. B lymphocytes fight infection and further mature into plasma cells. Plasma cells produce and release antibodies that are primed to attack and destroy germs. Multiple myeloma is a condition in which normal plasma cells convert to cancerous plasma cells.1

When a person has developed multiple myeloma, the plasma cells create excessive amounts of an abnormal antibody called the M protein that is not able to fight infection. This overgrowth of abnormal plasma cells overcrowds the bone marrow, impeding the growth of healthy blood cells such as white blood cells, red blood cells, and platelets. Because of this, people may initially present to their doctor with repeated infections, tiredness related to anemia (low red blood cells), and bleeding among other things. As the M protein accumulates in the urine and blood, damage to the kidney can occur.2

Why Did This Happen?

It is unclear why some people develop multiple myeloma and others do not. Age is a known risk factor, as 63% of new diagnoses are in people older than 65 years. Additionally, being a man and being African American are both risk factors. Exposure to certain substances such as asbestos, benzene, pesticides, or chemicals from the manufacturing of rubber can increase a person’s chances of developing the disease.2 Many people wonder if multiple myeloma runs in families. Although it is not considered a hereditary cancer (one that is passed on through families), having a parent or sibling with multiple myeloma may increase your chances of getting the disease. People who have monoclonal gammopathy of unknown significance, a condition that rarely causes symptoms, are at an increased risk of developing multiple myeloma of approximately 1% to 2% per year. Ultimately, around 30,000 people in the United States are diagnosed with multiple myeloma each year.3

“If you are facing the right direction, all you need to do is keep on walking.”

—Buddhist Proverb

What Is a Biomarker?

Biomarker is a term commonly tossed around in oncology settings. It refers to particular characteristics that can be accurately measured to confirm the diagnosis, indicate how aggressive the myeloma is likely to be, and assess response to treatment. These characteristics may include radiology tests such as x-rays, MRI or positron emission tomography (PET) scans, as well as blood tests and studies completed on a bone marrow biopsy specimen.

It has become increasingly common to use such biomarkers to help healthcare providers and patients understand the unique features of a cancer and to guide treatment decisions. Although not yet the case for multiple myeloma, in cancers, drug-related biomarkers have been developed that can predict the likelihood that a person will respond to a particular treatment medication.4

Biomarkers that Aid in the Diagnosis of Multiple Myeloma

When a diagnosis of multiple myeloma is suspected, a person is likely to undergo a series of tests that include various blood tests, collection of urine over a 24-hour period, a bone marrow biopsy, an x-ray to survey the bones in the body, and sometimes an MRI and/or PET scan.

Laboratory Testing

Blood work will likely consist of a serum protein electrophoresis (SPEP), which identifies the M protein (the abnormal protein that is being created in excess), and an immunoelectrophoresis, which establishes which antibody (for example IgA, IgE, or IgG) is detected by the SPEP. Immunoglobulins are the different types of antibodies the immune system churns out in the blood. A test of the quantitative immunoglobulins measures the quantity of these antibodies. It is common for someone with multiple myeloma to have a high level in one type of antibody and a normal or low level in the other types. Free light chains can be detected in the blood when the immunoglobulins break down into smaller parts (2 heavy chains and 2 light chains). The beta2-microglobulin is a measure of protein that can suggest the extent of the myeloma. An albumin level is typically a measure of overall health. The 24-hour urine collection is done to assess for the excessive abnormal protein in the urine. These tests are completed at regular intervals even after the diagnosis of multiple myeloma is made to make sure a treatment is working or to determine whether the multiple myeloma is progressing (getting worse).3

Bone Marrow Biopsy and Imaging

A bone marrow biopsy confirms the percentage of abnormal plasma cells present in the bone marrow. Having 10% or more plasma cells in the bone marrow is one of the criteria to diagnose active multiple myeloma. Some people have bone pain at the time of diagnosis of multiple myeloma. The disease causes breakdown of the bones and impairs new bone from forming, which can lead to lytic lesions. Radiology studies such as a bone survey, and MRI or PET scans, are often done to assess for these lesions, which are essentially areas that look like holes or have a Swiss cheese appearance on imaging.3

Additional Testing

A mutation is simply a change in a gene that happens because of an alteration in the DNA that is associated with that gene. When a person has multiple myeloma, it has occurred because their plasma cells developed mutations over their lifetime, causing the healthy cells to transform into cancer cells. These acquired mutations are specific to the cancer cells and therefore different than mutations that are present at birth and passed through families. The National Comprehensive Cancer Network (NCCN) recommends that testing to analyze chromosomes be performed on the bone marrow biopsy specimen. This is called cytogenetic and fluorescence in situ hybridization (FISH) testing. The information gleaned from these tests helps to further classify the multiple myeloma.5

The cytogenetic and FISH tests often reveal translocations or changes in the chromosomes. When a person with multiple myeloma is found to have a translocation of t(11;14) or t(6;14), it often projects a better prognosis. Other abnormalities, such as 17p deletion, t(14;16) and t(14;20), may indicate a higher-risk type of multiple myeloma. Having multiple genetic abnormalities is also considered high risk. High risk can mean more aggressive or not as likely to respond to standard treatments.6

What Stage Is It?

Staging multiple myeloma is much different than staging solid tumors like breast or lung cancer. The most commonly used staging system for multiple myeloma is the International Staging System (ISS). The ISS incorporates the previously discussed biomarkers and was recently updated to include lactate dehydrogenase (LDH) level and high-risk FISH abnormalities.7

International Staging System

Stage I: Beta2-microglobulin less than 3.5 mg/mL and albumin greater than 3.5 gm/dL. Absence of high-risk DNA abnormalities and normal LDH level

Stage II: Not stage I or stage III

Stage III: Beta2-microglobulin greater than or equal to 5.5 mg/ mL and high-risk DNA abnormality (17p deletion and/or translocation [4;14] or [14;16] or an elevated LDH level).

“Success is the sum of details.”

—Harvey S. Firestone

Prognosis Related to Biomarkers

Prognosis can be a scary word. Some might wonder why anyone would want to know whether they had standard-risk or high-risk multiple myeloma.The answer lies in the fact that understanding the specifics of each person’s multiple myeloma enables the optimal treatment plan to be created. It also allows you and your family to anticipate what’s ahead. Although multiple myeloma cannot typically be cured, it can be treated and managed over time. Having a higher-risk type of multiple myeloma may seem ominous, but the opportunity exists to optimize the situation by knowing. Research has shown that utilizing a treatment regimen that includes a proteasome inhibitor such as bortezomib can help to mitigate the effects of certain high-risk cytogenetics.8 Other risk factors for progression of disease are ISS stage III multiple myeloma, a higher than normal LDH level, and abnormal cytogenetics.9 Hemoglobin (red blood cells) level, percentage of plasma cells in the bone marrow, and kidney function are also important elements that impact prognosis.10

The International Myeloma Foundation11 proclaims, “No single test tells the whole story” on its website. It is important to remember this as you are digesting the specifics of your multiple myeloma. Various factors such as your age and overall health will also contribute to your prognosis. If you are looking for more detailed information about multiple myeloma and prognosis, NCCN Guidelines for Patients with Multiple Myeloma,12 Oncolink Penn Medicine, the Multiple Myeloma Research Foundation, and the Leukemia & Lymphoma Society are all reliable resources.

“The world is full of magical things patiently waiting for our wits to grow sharper.”

—Bertrand Russell

What’s on the Horizon?

The landscape of multiple myeloma is changing rapidly as new treatments are developed and the disease is better understood. Scientists are currently fielding and making sense of a large, evolving body of data about genetic mutations and their significance that is sure to influence how multiple myeloma is treated in the future. It is important that research continues through clinical trials and that multiple myeloma is approached according to its unique properties in each individual.

References

  1. Weaver CJ, Tariman JD. Multiple myeloma genomics: a systematic review. Semin Oncol Nurs. 2017;33:237-253.
  2. Multiple Myeloma Research Foundation. What is Multiple Myeloma? https://themmrf.org/multiple-myeloma/what-is-multiple-myeloma. 2019.
  3. Oncolink Penn Medicine. Multiple Myeloma: The Basics. www.oncolink.org/cancers/multiple-myeloma/multiple-myeloma-the-basics. 2019.
  4. Bhutani M, Landgren O, Usmani SZ. Multiple myeloma: is it time for biomarker-driven therapy? Am Soc Clin Oncol Educ Book. 2015:e493-e503.
  5. National Comprehensive Cancer Network Guidelines. Multiple Myeloma. www.nccn.org/professionals/physician_gls/pdf/myeloma_blocks.pdf. 2018.
  6. Richards T, Lee H. Multiple myeloma: risk stratification and toxicity management. J Adv Pract Oncol. 2018;9(3): 329-335.
  7. Leukemia & Lymphoma Society. Myeloma Staging. www.lls.org/disease-information/myeloma/diagnosis/myeloma-staging. 2019.
  8. Avet-Loiseau H, Leleu X, Roussel M, et al. Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol. 2010;28:4630-4634.
  9. Hu Y, Chen W, Chen S, Huang Z. Cytogenetic abnormality in patients with multiple myeloma analyzed by fluorescent in situ hybridization. Onco Targets Ther. 2016;9:1145-1149.
  10. Qian J, Jin J, Luo H, et al. Analysis of clinical characteristics and prognostic factors of multiple myeloma: a retrospective single-center study of 787 cases. Hematology, 2017;22:472-476.
  11. International Myeloma Foundation. www.myeloma.org. 2019.
  12. National Comprehensive Cancer Network Guidelines for Patients. Multiple Myeloma. www.nccn.org/patients/guide lines/myeloma/4. 2019.
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Last modified: June 12, 2019

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