What is multiple myeloma?

What is Multiple Myeloma

Multiple myeloma is a malignant plasma cell disorder characterized by clonal proliferation of abnormal plasma cells in the bone marrow that produce monoclonal immunoglobulin (M-protein) and cause end-organ damage. 1

Disease Epidemiology and Demographics

• Multiple myeloma accounts for approximately 1.8% of all cancers and more than 15% of hematologic malignancies in the United States, making it the second most common hematologic cancer 1, 2
• In 2020, an estimated 32,270 new cases were diagnosed in the United States, with approximately 12,830 deaths 1
• The median age at diagnosis is 69 years, with the disease most frequently diagnosed among people aged 65-74 years 1

Pathophysiology

• The disease results from neoplastic proliferation of plasma cell clones that accumulate in the bone marrow 1
• These malignant plasma cells produce monoclonal immunoglobulin (M-protein) that can be detected in serum and/or urine 1
• The malignant proliferation produces skeletal destruction leading to bone pain and pathologic fractures 3
• The M-protein can lead to renal failure, hyperviscosity syndrome, or through suppression of uninvolved immunoglobulins, recurrent infections 3

Clinical Manifestations: CRAB Criteria

Multiple myeloma presents with end-organ damage defined by the CRAB criteria 1, 4:

• Hypercalcemia: Serum calcium >11.5 mg/dL 4
• Renal insufficiency: Serum creatinine >2 mg/dL or creatinine clearance <40 mL/min 4
• Anemia: Hemoglobin <10 g/dL or ≥2 g/dL below lower limit of normal 4
• Bone lesions: Lytic lesions, severe osteopenia, or pathologic fractures on skeletal survey 4

Diagnostic Criteria

The diagnosis requires both of the following 1, 4:

• Clonal bone marrow plasma cells ≥10% or biopsy-proven plasmacytoma 1
• Evidence of end-organ damage (CRAB criteria) OR specific myeloma-defining biomarkers 1

Additional myeloma-defining biomarkers include 1:

• ≥60% clonal plasma cells in the bone marrow
• Involved/uninvolved free light chain ratio of ≥100
• More than one focal lesion on MRI

Required Diagnostic Workup

The National Comprehensive Cancer Network recommends the following initial tests 1:

• Complete blood count with differential and platelet counts
• Blood chemistry including calcium, creatinine, and β2-microglobulin
• Serum and urine protein electrophoresis with immunofixation
• Serum free light chain assay with kappa/lambda ratio
• Bone marrow aspiration and biopsy with CD138 staining
• Cytogenetic/FISH studies for risk stratification
• Full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging 2

Disease Spectrum and Classification

Multiple myeloma exists on a continuum 1, 4, 5:

• MGUS (Monoclonal Gammopathy of Undetermined Significance): Serum monoclonal protein <3 g/dL, clonal bone marrow plasma cells <10%, and absence of end-organ damage 4
• Smoldering Multiple Myeloma: Serum monoclonal protein ≥3 g/dL and/or clonal bone marrow plasma cells 10-60% without end-organ damage 1
• Symptomatic Multiple Myeloma: Presence of clonal plasma cells and evidence of end-organ damage (CRAB criteria) or myeloma-defining biomarkers 1
• High-Risk Multiple Myeloma: Characterized by specific cytogenetic abnormalities such as t(4;14), t(14;16), t(14;20), del(17p), or hypodiploidy 1

Clinical Presentation Statistics

At the time of presentation 2:

• Approximately 73% have anemia
• 79% have osteolytic bone disease
• 19% have acute kidney injury

Prognosis and Staging

The Revised International Staging System combines serum biomarkers (β2 microglobulin, albumin, and lactate dehydrogenase) with genomic features found on fluorescence in situ hybridization to assess prognosis 2:

• Stage I patients (28% at diagnosis) have a median 5-year survival of 82% 2
• The survival time range for patients with newly diagnosed multiple myeloma is 5 to 7 years, though the disease remains incurable in most patients 5, 6