Myeloma is a form of blood cancer caused by the excessive production of abnormal plasma cells in the bone marrow, the spongy tissue inside some bones where blood cells are generated.
Plasma cells protect the body against infections by producing antibodies. But these plasma cells, called myeloma cells, grow out of control and produce an abnormal antibody instead, called M protein, which can cause multiple complications.
While myeloma remains without a cure, its prognosis — or its likely course — has improved greatly in recent years due to the increased number of available treatments that can help in its effective management.
Several factors influence outcomes for myeloma patients, including prognostic indicators that help with myeloma staging, minimal residual disease, and relapsed and refractory disease.
Prognostic indicators include clinical and laboratory findings that help determine how fast the cancer is growing, the extent of disease, treatment response, and overall health status. Many of these tests are conducted multiple times throughout a patient’s journey.
Some diagnostic indicators include the cancer marker beta-2-microglobulin (B2M), whose levels rise with more extensive disease and poorer kidney function, and albumin, the most abundant protein in the blood and whose levels drop with myeloma progression.
LDH, an enzyme involved in energy production, is released into the blood when cells are damaged or destroyed, and higher LDH levels are indicative of greater damage and poorer outcomes. The amount of light chain — a small segment of the abnormal M protein produced by myeloma cells — is also associated with disease progression, with higher levels indicating a worse prognosis.
Patients who are younger at diagnosis tend to do better than those who are older, and the detection of myeloma before it greatly affects the kidneys is typically associated with a better prognosis. Health problems such as diabetes and heart disease may be associated with a poorer prognosis.
Staging of myeloma during diagnosis determines the extent of cancer progression and spread, and is important in deciding an effective treatment plan. Two methods are used to stage myeloma: the revised international staging system and the Durie-Salmon staging system.
International staging system
Myeloma is commonly staged using the revised international staging system (RISS), which is based on blood levels of albumin, B2M, and LDH, as well as specific genetic abnormalities in myeloma cells.
RISS divides myeloma into three stages. Stage I, the less aggressive form, is characterized by normal or close to normal levels of B2M (below 3.5 mg/L) and serum albumin (3.5 g/dL or more), normal LDH levels, and no high-risk genetic changes in myeloma cells. Stage III, the most aggressive form and one with the poorest prognosis, is defined by abnormally high B2M levels (5.5 mg/L or greater) in addition to high-risk genetic abnormalities in myeloma cells and/or high LDH levels. Stage II is given to patients whose results do not fit into either stage I or III.
Durie-Salmon staging system
The Durie-Salmon staging system is an older system that measures the amount of myeloma cells and the extent of damage, defined by the levels of hemoglobin and calcium in the blood, number of bone lesions, and the levels of M protein. It is then further categorized based on patients’ kidney function, which is often affected by myeloma.
Hemoglobin, the protein in red blood cells responsible for transporting oxygen, is usually reduced in myeloma patients due to impaired production of red blood cells in bone marrow that is crowded with myeloma cells. People with myeloma may also have higher-than-normal blood calcium levels due to excessive bone breakdown promoted by myeloma cells.
Minimal residual disease
Minimal residual disease (MRD) refers to the small number of myeloma cells still present in the bone marrow after treatment. These leftover myeloma cells may go on to divide and eventually cause disease relapse.
A patient is classified as MRD-negative if they achieve clinical remission and have less than one abnormal plasma cell per 100,000 cells collected from their blood or bone marrow.
The determination of MRD is an indicator of treatment success and is a prognostic factor, as patients who achieve a complete treatment response with no detectable MRD have better survival rates.
Relapsed and refractory disease
Myeloma that returns after a post-treatment period of remission is called recurrent or relapsed myeloma. In these cases, the cancer may need to be staged again to provide a new prognosis. Refractory myeloma refers to a cancer that does not respond to a therapy either initially or following a relapse, and it is associated with a poorer prognosis.
Last updated: Jan. 4, 2022, by Marta Figueiredo PhD
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