Multiple Myeloma

What is Multiple Myeloma?

Multiple myeloma is a cancer of plasma cells characterized by the clonal expansion of plasma cells that predominantly reside in the bone marrow. This population of malignant plasma cells secrete a characteristic monoclonal immunoglobulin (Ig), termed M-protein, which is used as biomarker for the diagnosis and disease monitoring of patients with MM. Multiple myeloma accounts for 1% of all cancers and approximately 10% of all hematologic malignancies. Each year over 32,000 new cases are diagnosed in the United States, and almost 13,000 patients die of the disease. Multiple myeloma is slightly more common in men than in women, and is twice as common in African-Americans compared to Caucasians. The median age of patients at the time of diagnosis is about 65 years.
(V Rajkumar, 2020)
Multiple Myeloma

Disease overview

Myeloma is caused by damage to DNA during development of the plasma cells in the bone marrow, causing them to divide uncontrollably. Plasma cells are responsible for producing antibodies to fight infections and other threats to the body. When a plasma cell becomes malignant, it proliferates and crowds out other healthy blood cells from the marrow. Malignant plasma cells can also make large amounts of antibodies, known as Monoclonal Proteins or M-Proteins or paraprotein which is also made up of heavy and light chains. Large amounts of this protein can cause symptoms and damage to organs. Multiple myeloma is not a single disease. There are wide variations of myeloma subtypes including inactive and active types of myeloma.

Monoclonal gammopathy of undetermined significance

MGUS is when abnormal plasma cells make an M protein but there are no symptoms. Almost all patients with Multiple Myeloma evolve from this asymptomatic pre-malignant stage. It is present in over 3% of the population above the age of 50 and the prevalence is approximately 2-fold higher in blacks compared to whites.
Over 50% of individuals who are diagnosed with MGUS have had the condition for over 10 years prior to the clinical diagnosis. MGUS progresses to MM or related malignancy at a rate of 1% per year.
Because MGUS patients may progress to myeloma, regular lab tests (every 3 to 6 months) can check for a further increase in the level of M protein or evidence of organ damage typically seen in active myeloma.

Smoldering Multiple Myeloma

In some patients, an intermediate stage referred to as smoldering multiple myeloma (SMM) can be recognized clinically. Smoldering myeloma is also asymptomatic and when compared to MGUS, has a larger M-protein in the blood or presence of more myeloma plasma cells in the bone marrow. SMM progresses to multiple myeloma at a rate of approximately 10% per year over the first 5 years following diagnosis, 3% per year over the next 5 years, and 1.5% per year thereafter.

Multiple Myeloma

Multiple myeloma comes in a variety of forms and is not a single disease. Bone disease is the main cause of morbidity. Major clinical manifestations are anemia, hypercalcemia, renal failure, and an increased risk of infections. Approximately 1% to 2% of patients have extramedullary disease (EMD)–which is when the tumor cells prolifirate outside of the bone marrow–at the time of initial diagnosis, while 8% develop EMD later on in the disease course.
Multiple Myeloma

Other plasma cell diseases
associated with Multiple Myeloma

In particular, the M-Protein is an important tumor marker used in the diagnosis and monitoring patient response to therapy. Since each plasma cell is programed to make only one uniquely shaped antibody, this tumor marker is unique to the malignant cell (other normal plasma cells make different shaped antibodies), and this antibody is unique to the patient. This individualized tumor marker is important for following the levels of malignant cells in the patient. There are other plasma cell diseases which are associated with Multiple Myeloma.

 
These include:
• Waldenström macroglobulinemia
• Amyloidosis (AL, AH, and AHL)
• Light Chain Deposit Disease
• POEMS Syndrome
• Plasma cell leukemia
• Cryoglobulinemia
 
Multiple myeloma accounts for 1% of all cancers and approximately 10% of all hematologic malignancies. Each year over 32 000 new cases are diagnosed in the United States, and almost 13 000 patients die of the disease. The median age of patients at the time of diagnosis is about 65 years. (V Rajkumar, 2020)