Multiple myeloma

Cancer of plasma cells

Multiple myeloma
Synonyms	N/A
Pronounce	N/A
Field	Hematology and oncology
Symptoms	Bone pain, fatigue
Complications	Amyloidosis, kidney problems, bone fractures, hyperviscosity syndrome, infections, anemia
Onset	Around 60
Duration	Long term
Types	N/A
Causes	Unknown
Risks	Obesity
Diagnosis	Blood or urine tests, bone marrow biopsy, medical imaging
Differential diagnosis
Prevention
Treatment	Steroids, chemotherapy, thalidomide, stem cell transplant, bisphosphonates, radiation therapy
Medication
Prognosis	Five-year survival rate 54% / life expectancy 6 years (USA)
Frequency	488,200 (affected during 2015)
Deaths	101,100 (2015)

Other Names: Plasma cell myeloma; Kahler disease; Myelomatosis; Plasma cell dyscrasia; Myeloma - multiple Multiple myeloma is a type of cancer characterized by the uncontrolled and abnormal growth of plasma cells in the bone marrow. These cells, which normally help the body fight infections by producing antibodies, grow excessively in multiple myeloma, disrupting the production of healthy blood cells and causing a range of health complications.

Micrograph showing myeloma cast nephropathy in a kidney biopsy: Hyaline casts are PAS positive (dark pink/red – right of image). Myelomatous casts are PAS negative (pale pink – left of image), PAS stain.

Atypical plasma cell infiltrate with both Russell (cytoplasmic) and Dutcher (nuclear) bodies (H&E, 50x)

Multiple myeloma in the upper arm

Skull X-ray showing multiple lucencies due to multiple myeloma

Bone marrow aspirate showing the histologic correlate of multiple myeloma under the microscope, H&E stain

A CT of the brain revealed a lytic lesion in the left temporal bone (right side of image), and petrous temporal bones involving the mastoid segment of the facial nerve canal. Red arrows: lesion; green arrow: normal contralateral facial nerve canal. The lesions are consistent with a myeloma deposit.

Pathological fracture of the lumbar spine due to multiple myeloma

Plasmacytoma, H&E stain

Micrograph of a plasmacytoma, H&E stain

X-ray of the forearm, with lytic lesions

Key Features

Many individuals with early-stage multiple myeloma may not experience any noticeable symptoms. However, when symptoms appear, the most common is anemia, which often leads to fatigue and shortness of breath. Other common signs and symptoms include:

• Recurrent infections
• Abnormal bleeding
• Bone pain and fractures
• Numbness or weakness in the arms and legs

The abnormal plasma cells in multiple myeloma produce dysfunctional proteins, also known as monoclonal proteins or M-proteins. These proteins contribute to various complications, such as:

• Reduced red blood cell count, leading to anemia
• Decreased white blood cell count (leukopenia), resulting in a weakened immune system
• Lowered platelet count (thrombocytopenia), causing abnormal bleeding and bruising
• Kidney damage due to toxic proteins and hypercalcemia

Illustration showing the most common site of bone lesions in vertebrae

Artist's depiction of myeloma cells producing monoclonal proteins of varying types

Impact on Bone Marrow

The accumulation of abnormal plasma cells in the bone marrow affects its ability to produce normal blood cells. This leads to a range of complications, including:

• Fatigue and pallor due to anemia
• Frequent infections from impaired immune function
• Easy bruising and bleeding from thrombocytopenia

These disruptions not only compromise the quality of life but can also lead to life-threatening complications if left untreated.

Importance of Early Detection

Early detection of multiple myeloma is critical to managing the disease effectively. For individuals without symptoms, routine blood or urine tests may reveal abnormalities that warrant further investigation. For symptomatic individuals, prompt diagnosis can prevent severe complications and improve treatment outcomes.

Causes and Risk Factors

Causes

The exact cause of multiple myeloma is not fully understood. However, the condition arises due to the abnormal and excessive growth of plasma cells in the bone marrow. These plasma cells normally produce antibodies to fight infections, but in multiple myeloma, they produce abnormal proteins (M-proteins) that cannot perform their usual functions.

Key processes in the development of multiple myeloma include:

• Genetic mutations: Abnormal exchanges of genetic material between chromosomes (translocations) are common in multiple myeloma. These changes often involve chromosome 14, affecting genes that regulate cell growth and division.
• Tumor formation: Excessive plasma cells cluster in the bone marrow, forming tumors that weaken bones and impair blood cell production.
• Immune dysfunction: The production of abnormal antibodies disrupts the immune system, leaving the body vulnerable to infections.

Risk Factors

Several factors are associated with an increased risk of developing multiple myeloma:

Genetic Factors

• A family history of monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma may increase the likelihood of developing the condition.
• Certain genetic mutations and chromosomal abnormalities are implicated in the disease, though these are typically acquired rather than inherited.

Environmental and Lifestyle Factors

• Age: The risk of multiple myeloma increases significantly in individuals over 60.
• Sex: Males are more likely to develop the condition compared to females.
• Race: African Americans are at higher risk than individuals of other racial backgrounds.
• Radiation exposure: Both medical radiation therapy and environmental radiation increase the risk.
• Chemical exposure: Prolonged exposure to carcinogens such as benzene—a chemical used in industrial solvents and gasoline additives—has been linked to multiple myeloma.
• Obesity: Excess body weight is a known risk factor.

Pre-existing Conditions

• Individuals with MGUS, a benign condition characterized by the presence of abnormal proteins in the blood, have a higher chance of progressing to multiple myeloma.

Understanding Risk

While these factors can increase the likelihood of developing multiple myeloma, not everyone with these risk factors will develop the disease. Similarly, some individuals with no apparent risk factors may still be affected. Research is ongoing to better understand the interplay of genetic, environmental, and lifestyle influences in the development of multiple myeloma.

Symptoms and Diagnosis

Symptoms

The symptoms of multiple myeloma can vary significantly from one individual to another. In the early stages, some individuals may have no noticeable symptoms. As the condition progresses, a wide range of signs and symptoms may develop, including:

Common Symptoms

• Anemia: Fatigue, shortness of breath, dizziness, and pallor due to a reduced red blood cell count.
• Bone pain: Often in the back or ribs, caused by bone lesions or fractures.
• Frequent infections: Resulting from a weakened immune system.
• Kidney dysfunction: Elevated serum creatinine and other indicators of kidney damage due to abnormal proteins and hypercalcemia.
• Abnormal bleeding: Easy bruising and prolonged bleeding from minor injuries due to thrombocytopenia.

Additional Symptoms

• Weakness and numbness in the arms or legs, sometimes caused by spinal cord compression.
• Nausea and loss of appetite.
• Weight loss and general malaise.
• Hypercalcemia: Symptoms include excessive thirst, constipation, and confusion.

Symptom Prevalence

• 80%-99% of affected individuals: Osteopenia and spontaneous bone fractures.
• 30%-79% of affected individuals: Acute kidney injury, increased IgG levels, and generalized muscle weakness.
• 5%-29% of affected individuals: - Functional gastrointestinal abnormalities, paresthesia (pins and needles sensation), and vertebral compression fractures.

Diagnosis

Diagnosing multiple myeloma involves a combination of clinical evaluation, laboratory tests, and imaging studies. The process typically includes:

Laboratory Tests

• Blood tests:
  • Complete blood count (CBC) to assess anemia and thrombocytopenia.
  • Serum protein electrophoresis (SPEP) and immunofixation to detect abnormal monoclonal proteins (M-proteins).
  • Blood chemistry studies to measure calcium and creatinine levels.
• Urine tests: - A 24-hour urine collection to detect Bence Jones proteins, a hallmark of multiple myeloma.

Imaging Studies

• X-rays: Detect bone lesions and fractures (skeletal survey).
• MRI and CT scans: Identify bone marrow abnormalities and soft tissue involvement.
• PET scans: Assess the spread and activity of cancerous cells.

Bone Marrow Examination

• Bone marrow biopsy and aspiration: Confirms the presence of abnormal plasma cells in the bone marrow and assesses the extent of disease.

Asymptomatic Diagnosis

In some cases, multiple myeloma is detected incidentally during routine blood or urine tests conducted for other reasons. Early detection, even in asymptomatic cases, is critical for preventing complications and initiating timely treatment.

Treatment and Prognosis

Treatment

The treatment of multiple myeloma is tailored to the individual based on factors such as age, overall health, the stage of the disease, and the presence of symptoms. While multiple myeloma is generally not curable, advancements in medical therapy have significantly improved outcomes. Common treatment approaches include:

Medical Therapies

• Chemotherapy: - Drugs like melphalan and cyclophosphamide are used to target and destroy rapidly dividing plasma cells.
• Corticosteroids: - Medications like dexamethasone and prednisone reduce inflammation and enhance the effects of other treatments.
• Targeted therapy: - Drugs such as bortezomib, carfilzomib, and ixazomib specifically target cancer cells with minimal harm to healthy cells.
• Biological therapy: - Agents like daratumumab and elotuzumab boost the immune system's ability to attack cancer cells.

Advanced Interventions

• Stem cell transplantation: - An autologous stem cell transplant involves using the patient’s own stem cells to rebuild healthy bone marrow after high-dose chemotherapy.
• Radiation therapy: - Used to treat localized bone pain or spinal cord compression.
• Surgery: - May be performed to stabilize fractures or relieve pressure on the spinal cord.

Watchful Waiting

For individuals with asymptomatic or smoldering multiple myeloma, close monitoring without immediate treatment may be recommended until the disease progresses.

FDA-Approved Medications

Several medications have been approved for the treatment of multiple myeloma, including:

• Melphalan (Alkeran®): For palliative treatment in patients unsuitable for oral therapy.
• Daratumumab (Darzalex): Used in combination therapies for newly diagnosed and relapsed patients.
• Carfilzomib (Kyprolis): Indicated for patients with prior therapies.
• Pomalidomide (Pomalyst): For patients with disease progression after previous treatments.
• Bortezomib (Velcade): A widely used proteasome inhibitor.

Prognosis

The prognosis for multiple myeloma varies depending on factors such as:

• The stage at diagnosis
• Response to treatment
• Presence of complications like kidney failure or infections

Complications

• Infections remain a leading cause of mortality, with affected individuals being seven times more likely to develop bacterial or viral infections.
• Bone fractures and hypercalcemia significantly impact quality of life and may worsen prognosis if not managed promptly.

Survival Rates

Recent advances in treatment have improved survival rates. Many patients achieve remission or long-term disease control with appropriate therapies. Ongoing clinical trials are exploring novel approaches to further enhance outcomes.

Supportive Care

In addition to medical treatment, supportive care plays a crucial role in managing symptoms and maintaining quality of life. This includes:

• Pain management
• Nutritional support
• Physical therapy for mobility and bone health
• Counseling and psychological support for coping with the disease

NIH genetic and rare disease info

• NIH info on Multiple myeloma

Multiple myeloma is a rare disease.

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