A.17 Multiple Myeloma

Question 1

A.17 Multiple Myeloma
Epidemiology:

Answer 1

Sex: ♂ > ♀ (3:2)
Peak incidence: 50–70 years

Question 1

A.17 Multiple Myeloma

Answer 1

Multiple myeloma is a malignancy of plasma cells that develops in the bone marrow and results in the production of high levels of immunoglobulin G (IgG) (55%) or immunoglobulin A (IgA) (26%).

Question 2

A.17 Multiple Myeloma
Classification:

Answer 2

Based on immunoglobulin type
* IgG and IgA: typical multiple myeloma; majority of patients
* Bence Jones myeloma (free light chains excreted in urine): 15–20% of multiple myelomas
* IgD, IgE, and IgM: very rare subtypes of multiple myelomas

Question 3

A.17 Multiple Myeloma
Pathophysiology:

Answer 3

Neoplastic proliferation of plasma cells
* Bone marrow infiltration by malignant plasma cells → suppression of hematopoiesis → leukopenia, thrombocytopenia, anemia
* Cell proliferation → pro-osteoclastogenic factors (e.g., TNF-α, IL-1, RANK-L) → osteolytic lesions → hypercalcemia

Overproduction of monoclonal immunoglobulin and/or light chains → dysproteinemia (a state of pathologically increased synthesis of immunoglobulins and/or their subunits) → kidney damage (e.g., myeloma cast nephropathy) and/or paraprotein tissue deposition (may cause amyloidosis) [3][4]
* Nonfunctioning antibodies → functional antibody deficiency
* ↑ Serum viscosity → hyperviscosity syndrome

Question 4

A.17 Multiple Myeloma
Clinical Features:

Answer 4

• Often asymptomatic
• Bone pain, often experiencing pain in the spine or back
• Fatigue, weakness, and marked weight loss
• Anemia
• Increased risk of infections
• Renal impairment
• Neurological symptoms, including paresthesia

Question 5

A.17 Multiple Myeloma
Staging (International Staging System)

Answer 5

The staging classification is based on the levels of β2-microglobulin and serum albumin:

Stage I: β2-microglobulin < 3.5 mg/L and serum albumin ≥ 3.5 g/dL
Stage II: Not falling into Stage I or III
Stage III: β2-microglobulin ≥ 5.5 mg/L

Question 6

A.17 Multiple Myeloma
Laboratory tests

Answer 6

CBC (with differential and peripheral smear)
* Anemia, thrombocytopenia, and/or leukopenia
* Decreased reticulocyte count
* Rouleaux formation
CMP
* Increased creatinine
* Hypercalcemia
* Elevated total protein with paraprotein (gamma) gap
Inflammatory markers: Increased ESR
Urinalysis: may be negative for protein

Question 7

A.17 Multiple Myeloma
Diagnosis Criteria

Answer 7

Main Criteria:
* ≥ 10% clonal bone marrow plasma cells in biopsy.
Plus at least one of the following:
1. Organ Damage (CRAB):
* Hypercalcemia: Calcium > 11 mg/dL.
* Renal Insufficiency: Creatinine clearance < 40 mL/min or serum creatinine > 2 mg/dL.
* Anemia: Hemoglobin < 10 g/dL.
* Bone Lesions: Identified on MRI.
2. ≥ 60% clonal plasma cells in bone marrow.
3. Involved/Uninvolved Serum Free Light Chain Ratio: Ratio > 1.
4. At least 1 focal lesion on MRI.

Question 8

A.17 Multiple Myeloma
Myeloma biomarkers

Answer 8

Blood tests
Immunoglobulin studies (common initial tests)
o Serum protein electrophoresis (SPEP): presence of M protein (M spike)
* Serum protein immunofixation: monoclonal gammopathy
* Serum free light chain assay (SFLC): increased κ or λ light chains, increased SFLC involved:uninvolved ratio
* Quantitative immunoglobulin levels (IgA, IgG, IgM) can help determine if proteinemia on SPEP is monoclonal.
Increased β2 microglobulin [9]
Increased LDH

Urine studies
Urine protein electrophoresis (UPEP) with immunofixation
* Bence Jones proteins: monoclonal immunoglobulin light chains produced by neoplastic cells
* Bence Jones proteinuria is suggestive of plasma cell disorders (e.g., multiple myeloma, Waldenstrom macroglobulinemia).
24-hour urine protein and creatinin

Question 9

A.17 Multiple Myeloma
Treatment Options

Answer 9

Asymptomatic Patients: Monitor with a “watch and wait” approach.

Symptomatic Patients:
Standard and Intermediate Risk:
Eligible for HSCT: Induction therapy followed by autologous HSCT.
Ineligible for HSCT: Induction therapy with corticosteroids (e.g., dexamethasone) and lenalidomide.

High-Risk Patients: Should participate in clinical trials.

Question 10

A.17 Multiple Myeloma
Supportive Therapy:

Answer 10

Osteolysis and Bone Pain: Managed with bisphosphonates and radiation therapy for osteolytic lesions.

Pancytopenia with Anemia: Treated with blood transfusions, G-CSF, and EPO.

Question 11

A.17 Multiple Myeloma
Monoclonal Gammopathy of Undetermined Significance (MGUS)

Differential Diagnoses

Answer 11

Definition: Identified by the presence of complete or incomplete monoclonal immunoglobulins (of any class) in individuals without accompanying clinical symptoms.

Epidemiology:
- Prevalence: Affects 3% of individuals aged 45–75 years.
- Common Type: Most frequently associated with plasma cell dyscrasias.

Diagnostic Criteria:
- Protein Levels: Monoclonal immunoglobulins detected at levels < 30 g/L.
- Bone Marrow: Clonal plasma cells constitute < 10% of bone marrow.

Complications:
- Can progress to multiple myeloma (approximately 1% of MGUS cases transform into multiple myeloma).

Treatment:
- No treatment necessary; monitor M-protein levels regularly.

Question 12

A.17 Multiple Myeloma
Waldenström Macroglobulinemia

Answer 12

Definition: A type of non-Hodgkin lymphoma characterized by the abnormal production of monoclonal IgM antibodies. It typically occurs in older adults and has an overall good prognosis.

Clinical Presentation
Symptoms:
- Peripheral neuropathy (often due to hyperviscosity syndrome).
- Impaired platelet function and hemorrhagic events (e.g., Raynaud phenomenon).
- Complications related to blood viscosity.
- Constitutional symptoms (e.g., fatigue, weight loss).
- Diagnosis:
- Initial tests: ESR, routine blood tests, and an APL.
- Imaging: Bone marrow biopsy showing increased clonal plasma cells and Dutcher bodies (PAS-positive).
- Additional assessment: Immunological analysis.
Complications
- Hyperviscosity Crisis: Increased blood viscosity can lead to various issues.
- Amyloidosis: Can occur when abnormal plasma cells produce amyloid proteins, leading to organ damage.
Skeletal Complications:
- Myeloma (multiple myeloma) can develop with renal dysfunction and may require treatment options like chemotherapy, plasmapheresis, or transplantation.
- Renal Involvement:
- Potential for renal impairment or chronic kidney disease in patients with multiple myeloma.
Transformation: In about 2–3% of cases, the condition can evolve into more aggressive forms.