Ola Landgren, Chief of the Myeloma Service at Memorial Sloan Kettering, explains how molecular profiling tests are used to analyze the biology of myeloma and personalize a patient’s care. There are many different subtypes of myeloma, all of which behave differently and require different treatment approaches. MSK doctors are refining the molecular profiling tools used to identify these subtypes and using this information to treat patients through clinical trials of new therapies.
If doctors suspect you have multiple myeloma, you may undergo a variety of blood, urine, bone marrow, and imaging tests. Your oncologist, radiologists, and pathologists will review these tests to help determine whether you have the disease, if it appears to be active, and how extensively it has spread throughout the body. Having an accurate diagnosis and assessment of your disease is the first step in getting the right care. It is very important that the diagnosis of multiple myeloma be well established before proceeding with any treatment.
Blood and Urine Tests
Compared with normal plasma cells, myeloma cells produce excessive amounts of immunoglobulin proteins. Blood and urine tests will measure such excessive protein and reveal the type of protein present, which may be different for each patient. Once it has been identified, the protein type serves as a unique marker for tracking progression of the disease and monitoring how well a patient is responding to treatment.
Myeloma cells also take over space in the bones where bone marrow grows, which reduces the number of normal red and white blood cells produced. Blood tests can measure the number of these cells to determine whether levels are abnormally low as well as reveal your level of kidney function and several other factors that indicate the extent of disease.
Bone Marrow Aspiration and Biopsy
During a bone marrow aspiration and biopsy, the patient receives local anesthesia, and a thin needle is inserted into the pelvic bone to remove some bone marrow for examination by a pathologist. Bone marrow aspiration removes a small amount of bone marrow fluid and cells. A bone marrow biopsy removes bone with the marrow inside. The two procedures are usually performed together, although in some cases you may need only an aspiration.
In a healthy person, plasma cells account for 2 to 3 percent of the cells in the bone marrow. A bone marrow biopsy containing more than 10 percent plasma cells is suggestive of multiple myeloma.
Pathologists also use the tissue taken in the biopsy to perform tests on the chromosomes of cancerous plasma cells removed from the bone marrow. Myeloma patients whose plasma cells contain chromosomal abnormalities usually have poorer outcomes than those with normal chromosomes — although certain chromosomal abnormalities are linked to a poorer prognosis than others while others are more benign.
Our physicians also use x-rays, MRI scans, and positron emission tomography (PET) to determine the number, size, and location of disease in the bone and other tissues, such as kidneys, muscles, the heart, and the digestive tract.
Determining the Extent of Disease
If your diagnostic tests confirm that you have multiple myeloma, your physicians will next need to determine the extent of your disease using the DSS (Durie-Salmon staging) system. The DSS stage reflects how much disease is present and whether it has affected your bones or organs — which, in turn determines whether you have asymptomatic or symptomatic myeloma. This information will help you and your doctors determine your treatment goals and select the therapy that offers you the best chance to control your disease.
Asymptomatic (Inactive) Myeloma
If you have no symptoms and no organ damage, you have what is called asymptomatic or inactive myeloma, also sometimes called smoldering myeloma. In this case, our physicians will monitor you closely for any changes that indicate the disease is becoming active. You may also receive vaccinations against infection and bone-strengthening medicines called bisphosphonates. Treatment targeting asymptomatic multiple myeloma is not usually given unless it is part of a clinical study.
If your protein levels start to rise steadily or you experience symptoms of bone damage, such as elevated calcium in the blood or signs of anemia or organ damage, the disease may have become active. At this point, your physician will likely begin treatment.
Symptomatic (Active) Myeloma
If you have myeloma symptoms or signs of organ damage, you have symptomatic or active myeloma and will need to receive treatment. For symptomatic myeloma your doctors will rely on the results of your blood tests to classify your disease as stage I, II, or III, using the International Staging System (ISS).
While the DSS stage is helpful in determining the extent of your disease, the ISS is used to determine prognosis. The ISS for myeloma, published in 2005, relies on measuring the levels of two components in the blood, beta 2 microglobulin (β2M) and albumin, which help doctors determine a patient’s prognosis.
New Diagnostic Approaches
Researchers at Memorial Sloan Kettering are developing new methods for assessing individual myeloma patients at the time of diagnosis. Using diagnostic tools such as a microarray analysis (which analyzes the expression of thousands of genes) or DNA sequencing to look for specific mutations thought to promote cancer progression, our doctors are investigating ways to better determine your prognosis and the treatments most likely to benefit you.