Multiple myeloma
Multiple myeloma is a clonal plasma cell neoplasm that produces a monoclonal immunoglobulin and end-organ damage summarized by CRAB (hypercalcemia, renal failure, anemia, bone lesions), diagnosed by marrow clonal plasma cells of 10% or more plus a CRAB or SLiM myeloma-defining event. Treatment combines a proteasome inhibitor, an immunomodulatory drug, and dexamethasone, followed by autologous stem cell transplant and maintenance in eligible patients.
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What this article covers
- Overview
Definition: multiple myeloma is a clonal plasma cell neoplasm in the bone marrow that secretes a monoclonal immunoglobulin (M protein) or free light chain and causes end-organ damage through bone…
- Epidemiology
Median age at onset is 65 years, essentially unheard of before middle age; more common in men and in African Americans.
- Risk factors
Age: incidence rises steeply after age 60; median age at diagnosis is 65 years.
- Pathophysiology
Clonal plasma cell expansion: a single post-germinal-center B cell clone proliferates in the marrow and secretes a single immunoglobulin isotype or free light chain, supported by marrow stromal…
- Clinical features
Bone pain, the most frequent presenting symptom, typically axial (back, ribs, pelvis) from lytic lesions, often precipitated by a pathologic fracture with normal use.
- Differential diagnosis
MGUS (monoclonal gammopathy of unknown significance): M protein under 3 g/dL, marrow clonal plasma cells under 10%, no CRAB features.
- Diagnosis
Establish the diagnosis with marrow clonal plasma cells at or above 10% (or a biopsy-proven bony or extramedullary plasmacytoma) plus a myeloma-defining event, a CRAB feature or a SLiM biomarker…
- Management
Confirm autologous stem cell transplant (HSCT) eligibility first, based on age, performance status, and comorbidity; this determines the induction regimen and overall sequence.
- Complications
Infection, the leading cause of death, from functional hypogammaglobulinemia and leukopenia; chemotherapy increases risk further.
- Prognosis
Median survival now approaches nearly 10 years from diagnosis with modern induction, transplant, and maintenance strategies, a major improvement over historical outcomes.
- Prevention
Bisphosphonate or denosumab in every active patient (zoledronic acid 4 mg IV monthly or denosumab 120 mg SC monthly) reduces skeletal events and improves survival; disease-modifying, not just symptom control.
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Related articles
- Monoclonal gammopathy of unknown significance
Monoclonal gammopathy of unknown significance (MGUS) is an asymptomatic, premalignant plasma cell disorder defined by a serum monoclonal protein under 3 g/dL, clonal marrow plasma cells under 10%, and no myeloma-defining end-organ damage. It is the most common plasma cell dyscrasia, progresses to multiple myeloma or a related malignancy at about 1% per year, and requires no treatment, only periodic surveillance.
- Amyloidosis
Amyloidosis is extracellular deposition of misfolded protein fibrils that stain apple-green with Congo red under polarized light, most often AL (clonal light chains, linked to plasma cell dyscrasias), AA (chronic inflammation), or ATTR (transthyretin, hereditary or wild-type). Diagnosis requires tissue biopsy for Congo red birefringence plus typing of the amyloid protein, and treatment targets the underlying source, plasma-cell-directed therapy for AL, inflammatory disease control for AA, and transthyretin stabilizers or silencers for ATTR.