Multiple myeloma (MM) is a cancer originating in the bone marrow, involving plasma cells. These specialized white blood cells produce antibodies to fight infection. In multiple myeloma, a single clone of plasma cells begins to multiply uncontrollably, producing an excessive amount of a single, non-functional protein.
This overgrowth of abnormal cells crowds out healthy blood-forming cells and releases substances that damage organs and bone. Because the disease is rooted in the blood-forming system, blood tests are an indispensable tool. They are used not only to raise the initial suspicion of the disease but also to establish a definitive diagnosis and monitor the effectiveness of treatment over time.
Early Indicators from Routine Blood Work
The first signs that something is amiss often appear on routine screenings, such as a Complete Blood Count (CBC) and a Comprehensive Metabolic Panel (CMP). The cancerous plasma cells proliferate within the bone marrow, the factory for all blood components. This crowding effect frequently leads to a reduction in healthy blood cell production.
A common finding is anemia (low red blood cell count), which results in fatigue and weakness. Less frequently, crowding may suppress platelet production, which is necessary for clotting. These non-specific abnormalities are often the first laboratory clues prompting a deeper investigation.
The CMP provides insight into organ function, revealing signs of myeloma’s impact. Elevated calcium levels (hypercalcemia) are frequently observed. This occurs because myeloma cells secrete signaling molecules that accelerate bone tissue breakdown, releasing calcium into the bloodstream.
Another finding on the CMP is evidence of kidney strain, indicated by elevated creatinine levels. The abnormal proteins produced by the myeloma cells can clog the filtering tubules of the kidneys, impairing their function. These initial results—anemia, hypercalcemia, and renal dysfunction—serve as important flags that guide the physician toward more specialized diagnostic tests.
Pinpointing the Monoclonal Protein
The definitive feature of multiple myeloma is the presence of a monoclonal protein (M-protein or paraprotein), produced by the clonal plasma cells. Specialized blood tests are needed to detect and characterize this abnormal protein. The initial test is typically Serum Protein Electrophoresis (SPEP).
SPEP works by separating the various proteins in the blood serum using an electrical current. Normal serum proteins create a smooth, distributed pattern across a gel, but the excessive, identical M-proteins produced by myeloma cells migrate together. This congregation forms a distinct, narrow spike, known as the “M-spike,” on the test graph.
While SPEP can detect and quantify the M-spike, it cannot identify the specific type of abnormal immunoglobulin. For confirmation and precise identification, Immunofixation Electrophoresis (IFE) is performed. This test uses specific antibodies against the different types of heavy chains (IgG, IgA, IgM) and light chains (kappa or lambda).
IFE confirms that the protein is indeed monoclonal and determines its exact composition, such as IgG kappa or IgA lambda. The presence of this identical, excessive protein in the blood is a direct biological signature of the underlying clonal plasma cell disorder.
Assessing Disease Activity and Organ Impact
Once the M-protein is identified, other blood markers gauge the extent of the disease, assess its aggressiveness, and track response to therapy. The Free Light Chain (FLC) assay is a highly sensitive test that measures the unbound kappa and lambda light chains circulating in the blood. These light chains are the smaller components of the M-protein that are often produced in excess by the myeloma cells.
The test’s primary value lies in calculating the ratio of kappa to lambda free light chains. A significantly skewed ratio, where one type is vastly more prevalent than the other, indicates the clonal overproduction characteristic of the disease. Unchecked free light chains, historically called Bence-Jones proteins, are small enough to be filtered by the kidneys, where they can precipitate and cause considerable damage.
Another prognostic marker is Beta-2 Microglobulin (B2M), a small protein found on the surface of most cells. Elevated levels of B2M in the blood suggest a higher overall burden of the myeloma cells and are an indicator of more aggressive disease. This marker is incorporated into the Revised International Staging System (R-ISS), a widely used framework for determining a patient’s prognosis.
A final marker, Lactate Dehydrogenase (LDH), is an enzyme found in many body tissues. High LDH levels are not specific to myeloma but can signal high tumor activity and rapid cell turnover, often correlating with more advanced or fast-growing disease. Together, these markers provide a comprehensive picture of the disease’s severity, guiding the choice of treatment and monitoring the patient’s progress.