Multiple myeloma (MM) is a cancer originating in plasma cells, a type of white blood cell responsible for producing infection-fighting antibodies. These malignant cells accumulate in the bone marrow, where they multiply and interfere with the production of normal blood components. Blood tests are a cornerstone of managing this disease, serving to identify initial indicators and continuously monitor disease activity and treatment effectiveness. The presence of abnormal proteins and disturbances in normal blood chemistry are the primary signals that prompt further investigation.
General Blood Chemistry Indicators
Initial indicators of multiple myeloma often appear on routine blood chemistry panels. Renal function tests, measuring blood urea nitrogen (BUN) and creatinine, frequently show abnormalities because excessive monoclonal proteins can damage the kidneys. Approximately 20% to 40% of patients have some degree of kidney impairment at the time of diagnosis, a condition sometimes termed myeloma kidney.
Another common finding is an elevated serum calcium level, known as hypercalcemia. This occurs because myeloma cells promote the breakdown of bone tissue, releasing calcium into the bloodstream. High calcium levels can cause symptoms like confusion, fatigue, and weakness, while also contributing to kidney damage by affecting the organ’s ability to excrete excess fluid.
A Complete Blood Count (CBC) often reveals anemia (low red blood cell count), which is common in nearly all myeloma patients. Anemia results from the malignant plasma cells crowding out the normal blood-forming cells within the bone marrow. The CBC may also show low counts of platelets (thrombocytopenia) and white blood cells (leukopenia) due to the same crowding effect. These markers alert clinicians to a systemic disease but are not specific enough for diagnosis.
Detecting the Monoclonal Protein
The definitive blood indicators of multiple myeloma involve detecting and measuring the monoclonal protein (M-protein), which is produced by cancerous plasma cells. Serum Protein Electrophoresis (SPEP) is often the first specific test used to screen for this abnormal protein in the blood. SPEP separates the various serum proteins based on their electrical charge and size, producing a characteristic pattern.
In a healthy person, the gamma region of the SPEP pattern shows a broad, diverse band reflecting the many different normal antibodies produced by plasma cells. When multiple myeloma is present, the SPEP reveals a dense, sharp peak in this region, known as the “M-spike” or “paraprotein.” This spike represents the overproduction of a single, identical type of antibody, which is the defining biochemical feature of the disease.
After detecting an M-spike via SPEP, Immunofixation Electrophoresis (IFE) confirms the exact class of the monoclonal protein. IFE uses specific antibodies to identify whether the M-protein is an immunoglobulin G (IgG), IgA, IgM, or another type. This information is crucial because the M-protein type can influence the patient’s prognosis and treatment plan.
A third, highly sensitive test is the Serum Free Light Chain (SFLC) assay, which measures the unbound kappa (k) and lambda (l) light chains circulating in the blood. Normal antibodies are composed of two heavy chains and two light chains, and in a healthy person, there is a small, balanced amount of excess free light chains. Myeloma cells overproduce one type of light chain, resulting in a markedly abnormal ratio of kappa to lambda light chains.
The normal kappa/lambda ratio typically ranges between 0.26 and 1.65, but a ratio significantly outside this range is a strong indicator of a monoclonal plasma cell disorder. The SFLC assay is particularly valuable for patients with non-secretory myeloma, a rare form where the intact M-protein is not detectable by SPEP. The abnormal free light chain ratio is the primary blood marker used for both diagnosis and monitoring in these cases.
Markers for Staging and Disease Activity
Once multiple myeloma is diagnosed, other blood markers assess the extent of the disease and predict the patient’s long-term outlook. Beta-2 Microglobulin (B2M) is a small protein shed by many cells, and its serum level correlates directly with the total mass of the tumor cells in the body. An elevated B2M level is generally associated with a higher disease burden and a poorer prognosis.
The B2M level is combined with the serum albumin level to establish the patient’s stage within the Revised International Staging System (R-ISS). Albumin is a major protein in the blood, and low levels often suggest advanced or aggressive disease. The R-ISS uses these two markers, along with other factors, to classify the disease into three stages, guiding treatment decisions.
Lactate Dehydrogenase (LDH) is another enzyme monitored in the blood; high levels can indicate greater tissue damage or a more aggressive form of myeloma. LDH is an independent prognostic factor and is also incorporated into the Revised International Staging System. Finally, general inflammation markers, such as C-Reactive Protein (CRP), may be tracked as they reflect myeloma activity or the presence of an infection.