Multiple myeloma

Multiple Myeloma

What is Multiple Myeloma?

Multiple Myeloma is a cancer that begins in plasma cells found in the bone marrow—the soft, sponge-like tissue inside bones where blood cells are produced. Plasma cells are essential components of the immune system, responsible for producing antibodies to fight infections. In multiple myeloma, these plasma cells grow uncontrollably, interfering with the production of healthy blood cells and reducing the body’s immune response.

When plasma cells multiply abnormally, they crowd out white blood cells (WBCs), red blood cells (RBCs), and platelets, causing several complications:

• Anemia: Decreased RBCs lead to fatigue and pallor.

• Bleeding: Low platelets result in excessive bleeding and bruising.

• Infections: Fewer WBCs make the body prone to infections.

• Low Immunity: Insufficient plasma cells weaken the immune system.

The cancerous plasma cells produce M protein or monoclonal protein, which can accumulate in the blood and urine, causing damage to organs such as the kidneys.

Statistics

• India: Annually, 14,641 cases of multiple myeloma are diagnosed, ranking 23rd among all cancers.

• Deaths: Approximately 12,556 deaths occur annually, placing it 18th in cancer mortality rates.

• Survival Rate: The 5-year survival rate in the United States is 58%.

Risk Factors

Several factors increase the risk of developing multiple myeloma:

• Age: Most cases occur in individuals over 60 years old; it is rare below the age of 40.

• Gender: Men are at a higher risk than women.

• Personal History: Those with solitary plasmacytoma (a single plasma cell tumor) may develop multiple myeloma later.

• MGUS (Monoclonal Gammopathy of Undetermined Significance): MGUS is a condition where plasma cells produce abnormal proteins without causing organ damage. Patients with MGUS are at increased risk of developing multiple myeloma over time.

Symptoms

• Fatigue and Weakness: Due to anemia from decreased RBCs.

• Bone Pain and Fractures: Myeloma cells weaken bones, increasing the risk of fractures.

• Tingling or Numbness: Compression of nerves in the spine can cause tingling or muscle weakness in the legs.

• Kidney Problems: M protein accumulation may impair kidney function.

• High Calcium Levels: Bone breakdown releases calcium into the bloodstream, causing fatigue, constipation, and kidney damage.

• Frequent Infections and Fever: Reduced immunity makes infections more common.

Diagnosis

• Blood and Urine Tests:

• M Protein Measurement: Detects M protein levels in blood or urine using serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP).

• Serum Free Light Chain Assay: Measures light chains (kappa or lambda) produced by plasma cells.

• Bence Jones Protein: Identified in urine when light chains are present.

• Bone Marrow Aspiration and Biopsy: A sample of bone marrow is examined to detect abnormal plasma cells.

• Imaging Tests:

• X-ray, MRI, PET-CT help identify bone lesions.

• Biomarker Testing:

• Cytogenetics and FISH (Fluorescence In Situ Hybridization) are used to identify genetic mutations associated with multiple myeloma.

Staging System

The Revised International Staging System (R-ISS) classifies multiple myeloma based on:

• Serum beta-2 microglobulin (β2-M) levels

• Serum albumin

• LDH (Lactate Dehydrogenase) levels

• High-risk chromosomal changes detected by FISH

• Stage I:

• Beta-2 microglobulin < 3.5 mg/dL

• Albumin ≥ 3.5 g/dL

• Normal LDH

• No high-risk chromosomal changes

• Stage II: Intermediate between Stage I and III.

• Stage III:

• Beta-2 microglobulin ≥ 5.5 mg/dL

• High-risk chromosomal changes

• Elevated LDH

Treatment Options

1. Chemotherapy

• Uses drugs to destroy cancer cells. Common drugs include cyclophosphamide, doxorubicin, melphalan, cisplatin, and bendamustine.

• Side Effects: Fatigue, infections, nausea, vomiting, hair loss, and reduced blood counts.

2. Targeted Therapy

• Focuses on specific proteins or genes in cancer cells.

• Common drugs: Bortezomib (Velcade), Carfilzomib (Kyprolis), Ixazomib (Ninlaro).

3. Immunotherapy

• Boosts the immune system to fight cancer cells.

• Drugs include Elotuzumab (Empliciti), Daratumumab (Darzalex), Selinexor (Xpovio).

• CAR-T cell therapies: Abecma and Carvykti.

4. Steroids

• Prednisone and dexamethasone are used to reduce plasma cell growth and inflammation.

5. Bone-Modifying Drugs

• Strengthen bones and reduce fractures:

• Bisphosphonates (Zoledronic acid, Pamidronate).

• Denosumab (Xgeva): Suitable for patients with kidney problems.

6. Radiation Therapy

• High-energy radiation is used to reduce pain and control localized tumors.

7. Bone Marrow Transplant (Stem Cell Transplant)

• Autologous transplant (AUTO): Uses the patient’s own stem cells.

• High-dose chemotherapy is followed by stem cell infusion to rebuild healthy bone marrow.

8. Surgery

• Rarely used as the primary treatment but may be necessary for bone fractures.

Management of Smoldering Multiple Myeloma (SMM)

SMM refers to an early-stage myeloma with no symptoms but a higher risk of progression. Treatment involves:

• Active Surveillance: Regular monitoring with blood tests and imaging.

• Induction Therapy: Initiated if symptoms appear, followed by consolidation (chemotherapy or transplant) and maintenance therapy to prevent relapse.

Follow-up Care

• Regular check-ups are essential to monitor disease progression and manage side effects.

• Blood tests, imaging scans, and bone marrow evaluations help ensure the cancer does not return.

• Supportive care is provided to manage long-term complications like infections or bone damage.

Multiple Myeloma is a complex and serious cancer of the bone marrow. While early detection and targeted treatment can improve outcomes, it remains a challenging disease. Advances in immunotherapy, chemotherapy, and bone marrow transplantation offer hope for better management and improved quality of life for patients. Regular follow-up and supportive care are crucial for maintaining health and preventing relapse.

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