Multiple Myeloma
A blood cancer involving malignant plasma cells in the bone marrow that causes bone destruction, kidney failure, anemia, and hypercalcemia.
Emergency Management: Spinal cord compression requires emergent MRI and high-dose dexamethasone (16 mg IV daily) followed by neurosurgery or radiation. Hypercalcemia crisis requires aggressive IV hydration and IV bisphosphonates.
Multiple myeloma is a hematologic malignancy characterized by the clonal proliferation of neoplastic plasma cells in the bone marrow. These malignant cells secrete monoclonal immunoglobulins (M-proteins), leading to organ dysfunction. It primarily affects the skeletal system, kidneys, and immune system.
Detailed Overview
The disease is driven by genetic mutations in post-germinal center B cells. It causes lytic bone lesions, hypercalcemia, renal failure, and anemia, collectively known as the CRAB criteria. The overproduction of monoclonal proteins (paraproteins) can cause cast nephropathy, while bone marrow infiltration suppresses normal hematopoiesis, leading to immunosuppression and cytopenias. Despite therapeutic advances, it remains largely incurable.
Epidemiology & Demographics
Incidence is approximately 7 per 100,000 annually in the US. The median age at diagnosis is 69 years. It is more common in men than women (1.4:1 ratio) and twice as common in individuals of African descent compared to those of European descent.
Etiological Mechanism
The exact cause is unknown, but it consistently evolves from an asymptomatic premalignant stage called monoclonal gammopathy of undetermined significance (MGUS). Specific cytogenetic abnormalities, such as t(11;14) or del(17p), play a crucial role in pathogenesis.
Primary Causes
Primary driver is the acquisition of genetic translocations (IgH locus on chromosome 14) or hyperdiploidy. Secondary factors include environmental exposures (radiation, benzene) and chronic immune stimulation.
Malignant plasma cells adhere to bone marrow stromal cells, triggering the release of cytokines like IL-6, which promotes myeloma cell growth and survival. These cells stimulate osteoclasts via the RANKL pathway and inhibit osteoblasts via DKK1, leading to osteolytic bone lesions and hypercalcemia. Monoclonal light chains are filtered by the glomerulus but precipitate in the renal tubules (combining with Tamm-Horsfall protein), causing light chain cast nephropathy.
Diagnostic Criteria & Guidelines
Requires >= 10% clonal bone marrow plasma cells or biopsy-proven bony/extramedullary plasmacytoma PLUS one or more myeloma defining events: CRAB features (HyperCalcemia > 11 mg/dL, Renal insufficiency CrCl < 40 mL/min or serum Cr > 2 mg/dL, Anemia Hb < 10 g/dL, Bone lesions >= 1) OR biomarkers of malignancy (>= 60% clonal BM plasma cells, involved/uninvolved serum free light chain ratio >= 100, or >1 focal lesion on MRI).
For transplant-eligible patients: Induction therapy with VRd (Bortezomib 1.3 mg/m2 SQ, Lenalidomide 25 mg PO daily, Dexamethasone 20-40 mg PO weekly) for 4-6 cycles, followed by autologous stem cell transplant (ASCT). For transplant-ineligible: Daratumumab, Lenalidomide, and Dexamethasone (DRd) continuously.
Second-Line & Adjunctive Therapy
Carfilzomib, Pomalidomide, and Dexamethasone (KPd) or bispecific T-cell engagers (e.g., Teclistamab) for relapsed/refractory disease. CAR-T cell therapy (Idecabtagene vicleucel) for patients with >= 4 prior lines of therapy.
Surgical & Procedural Management
Kyphoplasty or vertebroplasty for painful vertebral compression fractures. Orthopedic stabilization for impending pathologic fractures in long bones.
Patient Counseling & Advice
Educate on the signs of infection and the importance of prompt reporting, as infections are a leading cause of morbidity. Counsel on the teratogenic risks of lenalidomide (requires REMS program enrollment).
Follow-Up & Monitoring Schedule
Monthly evaluation of complete blood count, comprehensive metabolic panel, serum free light chains, SPEP, and UPEP during active treatment. Bone density scans (DEXA) annually.
Preventive Strategies
No primary prevention exists. Secondary prevention of bone events utilizes bisphosphonates (Zoledronic acid 4 mg IV monthly) or RANKL inhibitors (Denosumab 120 mg SQ monthly).
Median survival has improved to 5-7 years with novel agents. High-risk cytogenetics [del(17p), t(4;14), t(14;16)] reduce median overall survival to < 3 years.