Multiple Myeloma Overview

Multiple myeloma (MM), also known as Kahler’s disease, is a rare blood cancer that originates in plasma cells, a type of white blood cell found in bone marrow. Plasma cells play a crucial role in the body’s immune function by producing antibodies (immunoglobulins) to help fight off harmful invaders, such as bacteria, viruses and cancer. Immunoglobulins are made up of two heavy protein chains and two light protein chains, which work together to help the immune system defend against infections. In MM, abnormal plasma cells grow uncontrollably, disrupting normal blood cell production and compromising the immune system.

As cancerous plasma cells accumulate in the bone marrow, they may begin to crowd out healthy red blood cells, white blood cells and platelets. This can lead to a range of complications related to low blood cell counts, including anemia, recurrent infections and easy bleeding and bruising. Additionally, unlike healthy plasma cells that create functional antibodies, myeloma cells produce abnormal proteins known as monoclonal proteins (M proteins), which can build up in the bloodstream and damage the kidneys.

In the United States, multiple myeloma accounts for approximately 1% of all cancers and 10% of all blood cancers, with about 35,000 new cases diagnosed each year. While the condition can develop at any age, it primarily affects older adults. Through research and clinical trials, early detection and treatment of MM are continually improving, leading to better patient outcomes and quality of life.

What are the types of multiple myeloma?

MM is classified based on the type of immunoglobulins produced by the cancerous plasma cells. The types, which are signified by Greek letters, include:

• Gamma (IgG) – The most common type of multiple myeloma, IgG accounts for about 50% of cases.
• Alpha (IgA) – The second most common type of multiple myeloma, IgA accounts for 20 to 25% of cases.
• Delta (IgD) – An uncommon type of multiple myeloma, IgD predominantly affects younger patients and is associated with a more aggressive disease course.
• Mu (IgM) – Rare in multiple myeloma, IgM is more often associated with Waldenström macroglobulinemia, an uncommon type of non-Hodgkin lymphoma.
• Epsilon (IgE) – IgE is an exceedingly rare type of multiple myeloma.

Different immunoglobulins can have different effects on cancer progression, response to therapy and overall prognosis. Therefore, identifying the specific type of multiple myeloma is essential for developing the most effective treatment strategy.

What causes multiple myeloma?

Through extensive studies, scientists have linked MM to a genetic mutation in the DNA of plasma cells, which spurs uncontrolled cell growth and proliferation. As a result, abnormal plasma cells build up in the bone marrow, disrupting the production of healthy red blood cells, white blood cells and platelets. The ensuing imbalances can weaken the immune system, reduce oxygen transport, increase the risk of excessive bleeding and lead to other complications.

Despite significant advancements in cancer research, the precise cause of the genetic mutation that triggers the development of multiple myeloma is still unclear. While some cases may be influenced by aging, an inherited cancer predisposition syndrome or a harmful environmental exposure, no single cause has been conclusively identified. Understanding the molecular mechanisms behind the mutation remains a critical area of study, with the goal of developing more targeted and effective treatments for multiple myeloma.

If you suspect you may have myeloma, it is important to come to a high-volume program such as ours at Moffitt, so you can receive multispecialty care for this uncommon cancer.

Dr. Rachid Baz

Malignant Hematology Program

What are the risk factors for multiple myeloma?

Researchers have identified several factors that may increase the risk of developing MM. These include certain genetic, environmental and medical conditions, such as:

• Advanced age – The risk of multiple myeloma increases over time, with most cases diagnosed after age 65.
• Monoclonal gammopathy of undetermined significance (MGUS) – Many patients diagnosed with MM were initially found to have MGUS, a rare plasma cell disorder that can sometimes progress into multiple myeloma.
• Family history – Individuals with a parent, sibling or child diagnosed with MGUS or MM are two to three times more likely to develop multiple myeloma.
• Weakened immune system – People with human immunodeficiency virus (HIV) or human T-lymphotropic virus (HTLV), as well as those taking immunosuppressants after organ transplantation, face an increased risk of developing MM.
• Radiation exposure – Prior radiation therapy for another type of cancer may contribute to an increased risk of multiple myeloma.
• Chemical exposure – Prolonged contact with certain toxic substances, including insecticides, herbicides, petroleum products, heavy metals, plastics and asbestos, has been linked to a greater likelihood of developing MM.
• Occupational exposure – Studies suggest that workers in certain occupations may have an elevated risk of MM due to excessive exposure to harmful substances in the workplace. High-risk professions include farming, woodworking, painting, hairstyling, firefighting and jobs in the oil and gas, leather and rubber industries.

What are the symptoms of multiple myeloma?

MM symptoms tend to develop slowly and may not become apparent until the cancer reaches an advanced stage. The most common warning sign is bone pain, often in the spine and ribs. Other early symptoms of multiple myeloma can include:

• Appetite loss
• Constipation
• Excessive thirst
• Fatigue
• Nausea
• Recurrent infections
• Weakness
• Weight loss

Commonly referred to as CRAB symptoms, end-stage multiple myeloma may cause:

• C – Increased blood calcium levels
• R – Renal (kidney) dysfunction
• A – Anemia
• B – Bone lesions

How is multiple myeloma diagnosed?

MM can be challenging to recognize because it is typically asymptomatic in its early stages. In many cases, the condition is detected incidentally during routine blood work or urinalysis, which can identify abnormal proteins produced by myeloma cells.

To confirm a suspected diagnosis of multiple myeloma, the physician may use a combination of:

Imaging tests for multiple myeloma

Various imaging techniques can help detect bone damage or lesions caused by MM, including:

• X-rays – May show bone thinning or fractures
• Magnetic resonance imaging (MRI) – Can provide detailed visuals of bone marrow
• Computed tomography (CT) scans – May show structural bone abnormalities
• Positron emission tomography (PET) scans – Can reveal active myeloma cells in the body.

Bone marrow aspiration and biopsy for multiple myeloma

Because MM originates in bone marrow, a bone marrow biopsy and aspiration are essential for a conclusive diagnosis. During this combined procedure, the physician will collect samples of both the solid and liquid portions of the bone marrow. The samples will be sent to a lab for microscopic examination by a pathologist, who can identify abnormal plasma cells. In some cases, a lumbar puncture may also be performed to check for myeloma cells in the cerebrospinal fluid (CSF).

Molecular testing for multiple myeloma

If a bone marrow tumor is found, additional laboratory tests may be performed to check the cancerous cells for specific genes and proteins associated with MM. These tests can help the physician assess the aggressiveness of the cancer and predict its response to targeted therapies.

Advanced diagnostic techniques for multiple myeloma

Specialized laboratory tests can provide further insights that inform the diagnostic process for MM. These include:

• Cytogenetics – Can identify chromosomal abnormalities in myeloma cells
• Flow cytometry – Can measure the level of abnormal plasma cells in a liquid bone marrow sample
• Fluorescent in situ hybridization (FISH) – Can detect genetic mutations linked to multiple myeloma in plasma cells
• Serum and urine protein electrophoresis and immunofixation – Can find abnormal proteins associated with multiple myeloma
• Serum-free light chain testing – Evaluates the level of light chain proteins in the blood

How is multiple myeloma treated?

MM treatment can vary depending on the stage of the cancer, the overall health of the patient and other unique factors. Common treatment options include:

• Chemotherapy – Powerful cancer-fighting drugs enter the bloodstream and circulate throughout the body to target rapidly dividing myeloma cells, either destroying the cells or inhibiting their growth.
• Radiation therapy – High-energy beams are directed at a localized MM tumor or an area of bone damage to help relieve pain and prevent fractures.
• Chimeric antigen receptor therapy (CAR T-cell therapy) – A type of immunotherapy, CAR-T cell therapy can boost the ability of the patient’s own immune system to identify and destroy myeloma cells.
• Bone marrow transplantation – The patient’s cancerous bone marrow will be replaced with healthy bone marrow, which may be derived from the patient (autologous transplant) or a compatible donor (allogeneic transplant).

Unlike many other types of cancer that produce distinct masses, multiple myeloma is a systemic disease that is not usually treated with surgery. However, a surgical procedure may be incorporated into a supportive care plan to help alleviate the pain associated with a single, small tumor (solitary plasmacytoma) that forms when abnormal plasma cells build up in a bone or soft tissue.

Benefit from world-class care at Moffitt Cancer Center

Moffitt’s renowned Malignant Hematology Program offers the latest treatment options for multiple myeloma, with all services available in one convenient location. Our multispecialty team includes experts in all aspects of MM diagnosis, treatment and support. Working closely with the specialists in our Blood and Bone Marrow Transplant Program, each patient benefits from the best possible therapeutic options for their unique needs.

The scientists and clinicians at Moffitt are committed to continually exploring new and better ways to detect and treat multiple myeloma. In recognition of our extensive research efforts and groundbreaking clinical trials, the National Cancer Center designated Moffitt a Comprehensive Cancer Center, and we are the only cancer center based in Florida to have earned this noteworthy distinction.

If you would like more information about multiple myeloma, you can request an appointment with a specialist in the Malignant Hematology Program at Moffitt by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.

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