Multiple Myeloma

Overview

Multiple myeloma is a relatively uncommon cancer that develops in the bone marrow, the soft, spongy tissue found in the center of most bones. It begins in plasma cells, which are a crucial part of the immune system. Normal plasma cells help fight infections by producing antibodies that recognize and attack germs.

When plasma cells become cancerous and grow out of control, they produce abnormal proteins (M proteins or monoclonal proteins) instead of helpful antibodies. These cancerous cells can damage bones, the immune system, kidneys, and red blood cell count. The disease is called "multiple" myeloma because it frequently affects multiple areas of the body, such as the spine, skull, pelvis, and ribs.

Multiple myeloma accounts for approximately 1% of all cancers and about 10% of all hematologic malignancies. The disease typically affects older adults, with the average age at diagnosis being around 70 years. While multiple myeloma remains incurable for most patients, significant advances in treatment have substantially improved outcomes and quality of life.

Symptoms

Multiple myeloma symptoms can vary greatly from person to person, and some patients may have no symptoms at all in the early stages. When symptoms do occur, they often relate to the CRAB criteria (Calcium elevation, Renal insufficiency, Anemia, and Bone lesions). Common symptoms include:

The progression of symptoms often follows the accumulation of plasma cells and the production of abnormal proteins. Many patients experience periods of stability followed by periods of active disease, making symptom monitoring crucial for management.

Causes

The exact cause of multiple myeloma is not fully understood, but researchers have identified several factors that contribute to its development. The disease begins when a plasma cell undergoes genetic mutations that cause it to multiply rapidly and survive longer than normal cells.

Genetic Mutations

Multiple myeloma develops through a series of genetic changes in plasma cells. These mutations affect genes that control cell growth, division, and death. Common genetic abnormalities include:

• Chromosomal translocations involving the immunoglobulin heavy chain locus
• Deletions of chromosome 13 or 17p
• Gains of chromosomes 1q or chromosome 9
• Mutations in genes such as KRAS, NRAS, TP53, and BRAF

Disease Progression

Multiple myeloma typically evolves from precursor conditions:

• MGUS (Monoclonal Gammopathy of Undetermined Significance): A benign condition where abnormal proteins are present but don't cause symptoms
• Smoldering Multiple Myeloma: An intermediate stage with higher levels of abnormal proteins but still no symptoms
• Active Multiple Myeloma: The symptomatic stage requiring treatment

Environmental Factors

While not direct causes, certain environmental exposures may increase risk:

• Radiation exposure
• Certain chemicals like pesticides and petroleum products
• Obesity
• Chronic inflammation

Risk Factors

Several factors may increase the risk of developing multiple myeloma, though having one or more risk factors doesn't mean you will definitely develop the disease:

Diagnosis

Diagnosing multiple myeloma requires a combination of tests to confirm the presence of cancerous plasma cells and assess organ damage. The diagnostic process typically involves:

Blood Tests

• Complete Blood Count (CBC): Checks for anemia and other blood cell abnormalities
• Serum Protein Electrophoresis (SPEP): Detects abnormal proteins (M proteins) in blood
• Immunofixation: Identifies the specific type of abnormal antibody
• Serum Free Light Chain Assay: Measures light chain proteins
• Beta-2 Microglobulin: Helps determine disease stage and prognosis
• Lactate Dehydrogenase (LDH): Indicates cell turnover rate

Urine Tests

• 24-hour Urine Collection: Detects Bence Jones proteins
• Urine Protein Electrophoresis (UPEP): Identifies abnormal proteins in urine

Bone Marrow Tests

• Bone Marrow Aspiration and Biopsy: Essential for diagnosis, shows percentage of plasma cells
• Flow Cytometry: Analyzes cell characteristics
• Cytogenetics and FISH: Identifies genetic abnormalities

Imaging Studies

• Skeletal Survey (X-rays): Traditional method to detect bone lesions
• Low-dose Whole-body CT: More sensitive than X-rays
• MRI: Best for detecting spinal involvement
• PET/CT Scan: Shows metabolically active disease

Diagnostic Criteria

The diagnosis requires:

• ≥10% clonal plasma cells in bone marrow OR biopsy-proven plasmacytoma
• AND one or more CRAB features or biomarkers of malignancy

Treatment Options

Multiple myeloma treatment has evolved significantly, with many new therapies improving outcomes. Treatment is tailored to each patient based on age, overall health, disease stage, and genetic factors.

Initial Therapy

Drug Classes

Newer Therapies

• CAR-T Cell Therapy: Genetically modified T cells targeting BCMA
• Bispecific Antibodies: Engage T cells to attack myeloma cells
• Antibody-Drug Conjugates: Deliver chemotherapy directly to myeloma cells
• Novel Targeted Agents: Drugs targeting specific genetic mutations

Supportive Care

• Bisphosphonates: Strengthen bones and prevent fractures
• Radiation Therapy: For painful bone lesions or plasmacytomas
• Blood Transfusions: For severe anemia
• Antibiotics: Prevent or treat infections
• Pain Management: Various approaches for bone pain
• Physical Therapy: Maintain strength and mobility

Prevention

Currently, there are no proven ways to prevent multiple myeloma. The disease often develops from genetic changes that cannot be controlled. However, certain strategies may help reduce risk or detect the disease early:

Risk Reduction Strategies

• Maintain Healthy Weight: Obesity is a modifiable risk factor
• Limit Radiation Exposure: When possible, minimize unnecessary radiation
• Avoid Chemical Exposures: Use protective equipment when working with pesticides or industrial chemicals
• Regular Health Checkups: Important for those with MGUS or family history

Monitoring for High-Risk Individuals

People with MGUS or smoldering myeloma require regular monitoring:

• Regular blood and urine tests to check protein levels
• Periodic imaging studies
• Bone marrow biopsies when indicated
• Assessment for CRAB criteria

Lifestyle Considerations

• Maintain good overall health through diet and exercise
• Stay up-to-date with vaccinations to prevent infections
• Avoid smoking and excessive alcohol consumption
• Manage stress through healthy coping mechanisms

When to See a Doctor

Multiple myeloma can be challenging to diagnose early because symptoms may be vague or attributed to other conditions. Seek medical attention if you experience:

If you have been diagnosed with MGUS or smoldering myeloma, follow your doctor's monitoring schedule closely and report any new symptoms immediately.

Related Conditions

References

1. Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548-567.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 3.2023.
3. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046-1060.
4. Kumar SK, et al. Multiple myeloma. Nat Rev Dis Primers. 2017;3:17046.
5. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders. Br J Haematol. 2003;121(5):749-757.