Multiple myeloma: Clinical sciences

Multiple myeloma is a type of bone marrow cancer that originates in plasma cells, which are cells that develop from B lymphocytes to produce antibodies to fight infections. In multiple myeloma, plasma cells grow uncontrollably, crowding out the healthy cells in the bone marrow. As a result, the overgrowth of plasma cells can lead to a reduction in the production of other types of blood cells by the bone marrow. This can lead to anemia due to low red blood cell count, problems with blood clotting due to decreased platelets, and even a weakened immune system due to a decrease in functioning white blood cells.

Plasma cells also produce excessive monoclonal antibodies that are dysfunctional and, over time, can accumulate in tissues, such as the kidneys, causing renal failure. Additionally, these antibodies increase serum viscosity, which impairs normal blood flow. This is known as hyperviscosity syndrome.

Now, if your patient presents with a chief concern suggesting multiple myeloma, you should first obtain a focused history and physical examination. Most patients will be over the age of 65, and will likely report vague and nonspecific symptoms, such as weight loss, fever, and symptoms of anemia, including fatigue, weakness, shortness of breath, and dizziness. Some patients might also experience gastrointestinal symptoms, including nausea, constipation, or diarrhea. Others might report bone pain or a history of fractures or kidney disease. Finally, a person might experience symptoms of hyperviscosity syndrome, including blurred vision and headache.

On the physical exam, your patient will present with elevated temperature, tachycardia, pallor, and signs of fluid retention, like edema. They might also have bone tenderness or deformity, which are signs of pathologic fractures. Finally, the neurological exam can reveal findings like numbness, paresthesias, and weakness.

At this point, you can suspect multiple myeloma, so your next step is to order some tests. These include labs like CBC, CMP, peripheral blood smear, and serum free light chain or FLC assay, and protein electrophoresis from a 24-hour collection of serum or urine, respectively called SPEP and UPEP. In addition, you may want to order imaging, which may include skeletal survey, CT, PET/CT, and MRI.

Okay, so let’s look at your labs. CBC may reveal anemia or even pancytopenia, while CMP typically shows hypercalcemia and elevated creatinine. The peripheral blood smear typically reveals red blood cells stacked together, something like a roll of coins, often referred to as Rouleaux formation. This phenomenon occurs due to an increased concentration of plasma proteins that causes the cells to stick together.

Serum free light chain assay, SPEP, and UPEP can help detect monoclonal or M protein. M proteins, also known as paraproteins, are produced by a single clone of myeloma cells and represent abnormal immunoglobulins that can consist of both heavy and light chains, or light chains only. Moreover, the ones that consist of light chains only are called Bence-Jones proteins and are typically found in urine! The free light chain assay also measures the ratio between kappa and lambda light chains; in multiple myeloma, one type of light chain, either kappa or lambda, will be produced excessively, leading to a high FLC ratio.

Here’s a clinical pearl to keep in mind! You can also use M-protein to track disease progression and assess the patient’s response to treatment.