Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, renal insufficiency, and infections may occur. Complications may include hypercalcemia and amyloidosis. The cause of multiple myeloma is unknown. Risk factors include obesity, radiation exposure, family history, age and certain chemicals. There is an increased risk of multiple myeloma in certain occupations, due to occupational exposure to aromatic hydrocarbon solvents. Multiple myeloma is the result of a multi-step malignant transformation, and almost universally originates from the pre-malignant stage monoclonal gammopathy of undetermined significance (MGUS). As MGUS evolves into MM, another pre-stage of the disease is reached, known as smoldering myeloma (SMM). In MM, the abnormal plasma cells produce abnormal antibodies, which can cause kidney problems and overly thick blood. The plasma cells can also form a mass in the bone marrow or soft tissue. When one tumor is present, it is called a plasmacytoma; more than one is called multiple myeloma. Multiple myeloma is diagnosed based on blood or urine tests finding abnormal antibody proteins (often using electrophoretic techniques revealing the presence of a monoclonal spike in the results, termed an m-spike), bone marrow biopsy finding cancerous plasma cells, and medical imaging finding bone lesions. Another common finding is high blood calcium levels. Multiple myeloma is considered treatable, but generally incurable. Remissions may be brought about with steroids, chemotherapy, targeted therapy, and stem cell transplant. Bisphosphonates and radiation therapy are sometimes used to reduce pain from bone lesions. New approaches utilizing CAR-T cell therapy have been included in the treatment regimens. Globally, about 175,000 people were diagnosed with the disease in 2020, while about 117,000 people died from the disease that year. In the U.S., forecasts suggest about 36,000 people will be diagnosed with the disease in 2026, and about 10,850 people will die from the disease that year. In 2020, an estimated 170,405 people were living with myeloma in the U.S. Based on data from people diagnosed with the disease in the United States between 2016 and 2022, about 64% lived five years or more post-diagnosis. The disease usually occurs around the age of 60. It is uncommon before the age of 40. The word myeloma is from Greek myelo- 'marrow' and -oma 'tumor'.
Signs and symptoms
By the time most people are diagnosed with multiple myeloma, they have symptoms caused by cancer cells growing within the bone marrow. More than 80% have symptoms of bone damage at the time of diagnosis; this can manifest as bone pain and fractures. Bone pain can occur anywhere in the body, but most often involves the back, hips, or skull. Weakened bones in the spine can collapse, causing spinal cord compression that results in sudden back pain as well as numbness or weakness in the limbs. The breakdown of bone also leads to the release of calcium ions into the blood, leading to hypercalcemia and its associated symptoms.
Anemia The anemia found in myeloma is usually normocytic and normochromic. It results from the replacement of normal bone marrow by infiltrating tumor cells and inhibition of normal red blood cell production (hematopoiesis) by cytokines.
Impaired kidney function Impaired kidney function may develop, either acutely or chronically, and with any degree of severity. The most common cause of kidney failure in multiple myeloma is due to proteins secreted by the malignant cells. Myeloma cells produce monoclonal proteins of varying types, most commonly immunoglobulins (antibodies) and free light chains, resulting in abnormally high levels of these proteins in the blood. Depending on the size of these proteins, they may be excreted through the kidneys. These proteins and light chains can damage the kidneys. Increased bone resorption leads to hypercalcemia and causes nephrocalcinosis, thereby contributing to kidney failure. Amyloidosis is a distant third in the causation. People with amyloidosis have high levels of amyloid protein that can be excreted through the kidneys and cause damage to the kidneys and other organs. Light chains produce myriad effects that can manifest as the Fanconi syndrome (type II kidney tubular acidosis).
Infection Collateral infections are common with multiple myeloma since the disease impairs the functioning of blood components that normally resist pathogens. The most common infections are pneumonia, urinary tract infections, and sepsis. The greatest risk period for the occurrence of infection is in the initial few months after the start of new drug therapy, since many drug therapies further suppress the normal immune response. Infections (and "adverse events" for all diseases) are graded by a standardized scale. With some myeloma drug therapies, over 30% of people experience a "Grade 3" or higher infection (many people experience multiple such infections), calling for intervention at least by antibiotics. Of people who die within six months of their myeloma diagnosis, between 20% and 50% die from collateral infections. Clinical evaluation of a person's immune response is typically performed by a lab test that measures the levels of different immunoglobulins in the blood. There are five varieties of immunoglobulins, indicated by the suffices -A, -D, -E, -G and -M. In the aggregate, the immunoglobulin level may be elevated with the disease, but the majority of such increased antibodies are of a monoclonal variety due to the clonal plasma cell and are thus ineffective. Such ineffective antibodies are common of the immunoglobulin -A and -G varieties. When the measure of effective antibodies drops below a threshold (a condition termed hypogammaglobulinemia), supplemental immunoglobulins may be provided by periodic infusions to reduce the risk of collateral infections.
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