Multiple myeloma is a cancer of the plasma cells—white blood cells responsible for producing antibodies—that accumulate in the bone marrow. As malignant plasma cells proliferate, they crowd out healthy marrow elements, impair normal blood cell production, and release substances that damage bone. The result is an overabundance of abnormal proteins (M-proteins) in blood and urine, bone destruction, and impaired immunity.
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Bone Pain: Persistent ache, especially in the spine, ribs, and pelvis, due to bone lesions or fractures
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Anemia‐Related Fatigue: Weakness, shortness of breath, or lightheadedness from low red‐cell counts
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Frequent Infections: Weakened immunity leads to recurrent respiratory or urinary tract infections
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Kidney Dysfunction: Elevated creatinine or protein in urine (Bence Jones protein) causing reduced kidney function
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Hypercalcemia Signs: Excess calcium in blood—nausea, constipation, increased thirst, confusion
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Genetic Abnormalities: Chromosomal translocations and mutations—such as t(4;14), t(11;14), or del(17p)—drive malignant transformation of plasma cells.
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Chronic Antigenic Stimulation: Long‐standing immune stimulation (e.g., chronic infections) may increase risk, although exact triggers remain under study.
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Environmental & Occupational Exposures: Exposure to benzene, pesticides, and radiation is linked to higher incidence.
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Age & Gender: Risk rises after age 60; slightly more common in males.
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Family History: A first‐degree relative with multiple myeloma or related plasma‐cell disorders increases personal risk.
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Immune Dysregulation: Declining immune surveillance can allow clonal plasma cells to expand unchecked.
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Bone Marrow Microenvironment Changes: Alterations in stromal cells and cytokine milieu (e.g., elevated IL-6) promote malignant cell survival.
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Renal Impairment: Worsening kidney function leads to accumulation of toxic proteins, exacerbating plasma‐cell growth.
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High Calcium Levels: Bone breakdown releases calcium, which feeds back to increase tumor cell activity.
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Secondary Genetic Events: Additional mutations over time accelerate disease progression and resistance to therapy.
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Serum & Urine Protein Studies:
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Serum Protein Electrophoresis (SPEP): Detects monoclonal (M) protein spike in blood.
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Immunofixation Electrophoresis: Identifies specific immunoglobulin type (IgG, IgA, etc.).
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Free Light Chain (FLC) Assay: Measures kappa and lambda light chains; abnormal ratio suggests light‐chain disease.
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24‐Hour Urine Protein Electrophoresis: Identifies Bence Jones proteins (light chains) excreted in urine.
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Bone Marrow Examination:
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Aspiration & Biopsy: Confirms clonal plasma cells ≥10% of marrow cellularity; assesses cytogenetic abnormalities.
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Imaging Studies:
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Skeletal Survey (X-rays): Reveals lytic lesions, fractures, or bone thinning.
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MRI or PET/CT: Detects focal lesions, spinal cord compression, or extramedullary disease.
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Laboratory Tests:
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Complete Blood Count (CBC): Assesses anemia, thrombocytopenia, or leukopenia.
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Serum Creatinine & Calcium Levels: Evaluate kidney function and detect hypercalcemia.
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β2-Microglobulin & Albumin: Provide staging information (International Staging System) to estimate prognosis.
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First‐line therapy for eligible patients often combines a proteasome inhibitor (e.g., Bortezomib 1.3 mg/m² twice weekly for two weeks every 21 days) with an immunomodulatory agent (e.g., Lenalidomide 25 mg daily on days 1–21 of a 28-day cycle) and a corticosteroid (e.g., Dexamethasone 20 mg on treatment days). This triplet approach reduces tumor burden and improves marrow function. For transplant‐eligible individuals, induction therapy is followed by high-dose melphalan conditioning (200 mg/m²) and autologous stem cell transplant; maintenance therapy with a single agent (e.g., Lenalidomide 10–15 mg daily) thereafter prolongs remission. In transplant‐ineligible or frail patients, a two-drug regimen (Bortezomib plus Dexamethasone) or reduced-intensity combinations are preferred. At relapse, second-generation proteasome inhibitors (Carfilzomib 20 mg/m² escalating to 36 mg/m²) or monoclonal antibodies (Daratumumab 16 mg/kg weekly for eight weeks, then biweekly) provide additional options. Supportive care—including bisphosphonates (Zoledronic acid 4 mg IV every 4 weeks) to strengthen bone, and erythropoietin‐stimulating agents for anemia—addresses complications and improves quality of life.
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How is multiple myeloma different from other blood cancers?
Multiple myeloma specifically affects plasma cells in the bone marrow, leading to overproduction of monoclonal proteins, bone destruction, and kidney damage. In contrast, leukemia involves immature white blood cells in blood and marrow, and lymphoma affects lymph nodes or lymphatic tissues.
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What factors guide the choice of initial therapy?
Treatment decisions consider patient age, overall health, renal function, and candidacy for transplant. Younger, fit individuals typically receive aggressive triplet induction followed by high-dose therapy and stem cell rescue, whereas older or medically frail patients may start with less intensive doublet regimens.
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Can multiple myeloma be cured?
Although a definitive cure is rare, many patients achieve deep remissions and prolonged survival with modern therapies. Maintenance strategies and newer agents continue to extend progression-free intervals, with some patients living beyond 10 years.
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Why are bone-strengthening agents important?
Malignant plasma cells stimulate bone breakdown, causing lytic lesions, fractures, and hypercalcemia. Bisphosphonates (e.g., Zoledronic acid) or RANKL inhibitors (Denosumab 120 mg SC monthly) reduce skeletal complications by inhibiting osteoclast activity and improving bone density.
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What monitoring is required during treatment?
Regular assessments include SPEP and FLC assays every cycle to measure response, CBC and metabolic panels (renal and calcium levels) monthly, and imaging (MRI/PET) at baseline and as clinically indicated. Post-transplant, surveillance continues to detect minimal residual disease and guide maintenance therapy.
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