Myeloma is a tumor of the bone marrow. Although described in the news media, there is a lack of public awareness of myeloma. This brochure has been developed to provide some basic knowledge about the disease and treatment recommendations. It provides basic knowledge of myeloma sufficient to enable patients to make decisions about treatment options, and it supplements the information provided by physicians. Caregivers, family members, and friends of the patient will be able to obtain useful information from it. Wang Luqun, Department of Hematology, Qilu Hospital, Shandong University Although myeloma is not yet curable, there are a number of treatment options that allow patients to survive long-term. Many patients can survive for years or even decades after a diagnosis of myeloma. With intensive research, the overall treatment outlook for patients is improving. The better the understanding of the disease and the clarity of what can be done to help the disease, these can ease concerns about the disease and can facilitate the diagnosis. Myeloma is a disease that varies relatively widely among individuals. Myeloma mostly progresses slowly, but can sometimes be more aggressive. While physicians recommend the best treatment for each patient, the patient plays a central role in making individualized treatment decisions. It is important for patients and families to have a good understanding of the disease and to be able to ask questions as well as to engage in careful thought about the choice of treatment strategy. What is myeloma? Myeloma is literally a “tumor,” or neoplasm, involving the “bone marrow,” or the blood-forming cells in the bone marrow. These cells are plasma cells (a type of white blood cell), which are the cells that produce our antibodies (immunoglobulins). Malignant or cancerous plasma cells are called myeloma cells. Myeloma is called “multiple” because the bones attacked by the tumor often form multiple lesions. A single bone lesion is called an “isolated myeloma”. Myeloma involves bone marrow that is still normally active in blood production in adulthood. This active marrow is usually found in the hollow areas of the bones of the vertebrae, skull, pelvis, ribs, and shoulder and hip joints. The hands, feet, forearms, and lower legs are not usually involved. The hematopoietic function of these areas is usually adequately preserved. Myeloma can be detected in the pre-cancerous stage (see Table 1). In some cases the tumor cells in the bone marrow grow very slowly. The earliest stage is called monoclonal immunoglobulinemia of undetermined significance (MGUS). At the MGUS stage, the myeloma cells are still below 10% of the bone marrow cells. The risk of transformation from MGUS to myeloma is very low: approximately only 1%. Both MGUS and this inert myeloma develop very slowly over several years and do not require active treatment. Therefore, it is important to properly differentiate between the two conditions, MGUS and inert myeloma, and active symptomatic myeloma that requires aggressive treatment. Although some factors may cause or predispose to myeloma, the exact mechanism is not known. High-risk factors and associated diseases for myeloma include toxic chemicals (e.g., pesticides and oranges used in the Vietnam War and some petrochemical compounds), radiation (including atomic radiation), and several viral infections (human immunodeficiency virus HIV, hepatitis virus, human herpes virus-8, etc.). Myeloma does not show a clear familial predisposition; however, a few families have a susceptibility. Myeloma occurs in adults. The average age of myeloma onset is 60 years. Only 5-10% of patients develop the disease before the age of 40. Myeloma is most common in men and certain ethnic groups, such as African Americans. There are approximately 20,000 new cases of myeloma in the United States each year. The incidence rate is about 0.5-1/100,000 in Asians and 10-12/100,000 in African Americans, with nearly 100,000 myeloma patients being treated in the United States at any given time. Our annual incidence rate is approximately 1 in 100,000. Why is it important to treat myeloma? Untreated myeloma can lead to bone destruction, elevated blood calcium, decreased blood counts (especially anemia), susceptibility to infection, and impaired kidney function. Because the spine is often involved and the proteins produced by myeloma can damage nerves, there is often an urgent need to address spinal and neurological problems. When treating myeloma, it is important to distinguish between urgent situations such as bone destruction, infection, renal impairment or nerve compression and the overall treatment plan. Sometimes the management of emergencies cannot and should not be delayed. However, patients should be encouraged to seek early consultation with a hematologist or oncologist who understands myeloma. For example, emergency surgery or radiation therapy may be an option. All treatment options must take into account the feasibility of future treatment. Once the emergency has been managed, a detailed overall treatment plan can be discussed. There is usually time to find a second treatment option or consult with a specialist to ensure that all options have been carefully considered. Even if the treatment plan is clear, if there are any concerns, problems or questions, it is best to address them as early as possible. It is extremely important to develop a mutually satisfactory treatment plan with your primary care physician. What causes myeloma medical problems Normal plasma cells produce immunoglobulins, a complex protein we call “antibodies. Myeloma cells do not produce functional antibodies, but rather a clonal protein, or “monoclonal protein” of immunoglobulins. All myeloma-related medical problems are caused by the proliferation of myeloma cells (see Table 2). Unlike other types of cancer, myeloma patients can have many strange complications because myeloma cells not only form tumor tissue, but they also release many proteins and other chemicals into the bone marrow microenvironment or directly into the bloodstream. ● Local effects on the bone marrow Local effects on the bone marrow include decreased blood cell production and damage to the surrounding bone mass. These effects result in common features of myeloma, such as anemia, susceptibility to infection, bone pain, fractures, and elevated blood calcium. The effects outside the bone marrow are primarily due to the production of monoclonal immunoglobulins by myeloma cells. As myeloma cells accumulate in the bone marrow, myeloma-specific immunoglobulins or antibodies are released into the blood circulation. This myeloma cell-produced specific immunoglobulin or monoclonal protein causes damage to distant organs; for example, renal function impairment is not uncommon. The protein can also affect blood clotting or interfere with circulation and can cause damage to other organs or tissues. Treatment of myeloma can inhibit tumor growth on the one hand and reduce the various effects caused by the proteins and chemicals produced by myeloma on the other. Types of myeloma Myeloma is divided into different types and subtypes. These classifications are based on the type of immunoglobulin produced by myeloma cells. Under normal circumstances, different immunoglobulins have different functions in the body. Each immunoglobulin is composed of two heavy chains and two light chains. (See Figure 1). There are 5 types of heavy chains: G,A,D,E and M. There are 2 types of light chains: κ and λ. The type of myeloma can be clarified by fixation immunoelectrophoresis (IFE) test by heavy and light chains. About 65% of myeloma patients are IgG type (i.e., heavy chain is G and light chain is κ or λ). IgM, IgD and IgE types are very rare. Almost 30% of patients produce light chains present in the urine (e.g., light chain κ), while both light and heavy chains are present in the blood (e.g., IgG κ). About 10% of patients produce only light chains and do not form heavy chains; this type of myeloma is called “light chain” or “periosteal” myeloma. In even fewer cases (about 1-2% of patients), myeloma cells produce very few, if any, monoclonal proteins, called “non-secretory” myeloma. However, the Freelite test (serum free light chain assay) is able to detect trace amounts of light chains in most of these cases. The clinical presentation of the different types of myeloma differs only slightly; IgG myeloma presents with the usual myeloma manifestations; IgA myeloma is sometimes characterized by the formation of tumors outside the bone; IgD type can be associated with plasma cell leukemia and more often causes kidney damage. Light chains or periosteal myeloma are most likely to destroy the kidney, and light chains can be deposited in the kidney and/or nerves and other organs. This type is called amyloid or light chain deposition, based on the characteristics of light chain deposition. Staging of myeloma The number of myeloma cells in the body at the time of myeloma diagnosis varies from person to person. This is the staging of myeloma. The most common staging criteria used in the past are shown in Table 4, which indicates the degree of progression and destruction of myeloma, such as bone disease and anemia. Early initiation of treatment and aggressive avoidance of bone disease and other complications can improve the prognosis. The most commonly used staging criteria are shown in Table 5, which is the result of a collaborative effort of more than 20 worldwide research working groups. A number of tests are available to assess disease progression in a given myeloma patient. Often, elevated or abnormal test results predict more active myeloma and make it difficult to achieve prolonged remission.