Multiple Myeloma : Quick Approach

Plasma cell dyscrasia refers to an abnormal proliferation of plasma cells that usually secrete a monoclonal immunoglobulin.

A) CLINICAL FEATURES

Features vary among various conditions:

Mnemonic: CRAB Infection

1. Calcium increased:

• Hypercalcemia
• Nephrocalcinosis

and

Coagulopathy: Inhibition of or antibody against clotting factor; antibody-coated platelets

2. Renal failure or Renal Tubular Acidosis type II: Causes include –

• Bence-Jones Proteinuria
• Nephrocalcinosis
• Amyloidosis
• Hyperuricemia
• UTI
• Infiltration by myeloma cells

3. Anemia, Leukopenia, Thrombocytopenia

and

Amyloidosis

4. Bone:

• Swelling
• Pain
• Compression myelopathy
  • POEMS syndrome: Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes

5. Infections: due to hypogammaglobulinemia

6. Hyperviscosity:

• Blurring of vision
• Headache
• Vertigo
• Nystagmus

6. Other: Peripheral neuropathy, Myelomatous meningitis

B) INVESTIGATIONS

• CBC: Pancytopenia, Increased ESR
• PBS: Rouleax formation
• Biochemistry profile:
  • ↑ Calcium
  • ↑ Urate
  • Deranged RFT
  • Electrolytes
  • ALP ↑/=
  • ↓ Protein; ↑ Albumin and ↓ Globulin
• Serum protein electrophoresis (SPEP): Quantifies M-protein (positive in 80%)
• Urine protein electrophoresis (UPEP): Detects 20% patients who are light chain secretors (BJ proteins)
• Immunofixation: Shows component is monoclonal and identifies immunoglobulin type –
  • IgG (50%) > IgA (20%) > IgD (2%) > IgM (0.5%)
  • Light chain only (20%)
  • Non-secretors (1%) – plasma cells cannot excrete immunoglobulin molecule
• Serum free light chain assay: diagnosis and follow-up of treatment response
• β2 microglobulin and LDH: tumor burden
• Bone marrow biopsy:
  • better prognosis = hyperdiploidy
  • worse prognosis = deletion of chromosome 17p13 (10%) and certain translocations
• Skeletal survey: Plain radiographs to identify lytic bone lesions and pathological fractures; bone scan is not useful in diagnosing lytic lesions

C) DIAGNOSTIC CRITERIA OF MULTIPLE MYELOMA

International Myeloma working group Diagnostic criteria: ≥2 of –

1. Asymptomatic:

• M-protein ≥ 3 gm/dl and/or
• Bone-marrow plasma cells ≥ 10%

2. Symptomatic: + ≥1 of CRAB

• Corrected Calcium ≥ 11.5 mg/dl
• Renal failure (Creatinine > 2 mg/dl)
• Anemia (Hb < 10 gm/dl)
• Bone (multiple lytic lesions/osteopenic)

D) VARIANTS

• 1 bone lesion, normal bone marrow, normal uninvolved immunoglobulins: biopsy shows solitary plasmacytoma
• Soft tissue mass (Upper respiratory tract, GI), No bone lesion, Normal bone marrow: Biopsy shows Extramedullary plasmacytoma
• No CRAB: Asymptomatic/Smoldering multiple myeloma
• Normal CBC and chemistries, Bone marrow ≤ 10% plasma cells, No lytic lesions, M component < 3 gm/dl, Normal uninvolved Immunoglobulins, Often normal UPEP: Monocloncal Gammopathy of Undetermined Significance (MGUS)
• Waldenstorm Macroglobulinemia:
  • lymphoplasmacytic lymphoma (B-cell neoplasm secreting monoclonal IgM)
  • like MGUS – no evidence of lytic bone lesions
  • Fatigue (anemia)
  • Tumor infiltration: bone marrow (cytopenia), hepatomegaly, splenomegaly
  • Circulating monoclonal IgM: hyperviscosity, type I cryoglobulinemia (Raynaud’s phenomenon), platelet dysfunction (mucosal bleeding)
  • IgM deposition: Amyloidosis, Glomerulopathy
  • Autoantibody activity of IgM: chronic AIHA, neuropathy (IgM against myelin-associated glycoprotein)

E) STAGING

Durie Salmon staging mnemonic: ABCdE

1. Anemia: >10 to <8.5
2. Bony lesions: <2 to Advanced
3. BJ proteins (urine light chain): <4 gm/24 hr to >12 gm/24 hr
4. Calcium degree: <12 to >12
5. Electrophoresis:
   • IgG: <5 to >7
   • IgA: <3 to >5

F) TREATMENT

1. General treatment:

Plasmapheresis for hyperviscosity

2. Specific treatment:

a. Multiple myeloma: Chemotherapy ± Radiotherapy (for local problems) ± Autologous stem cell transplant (in <65 years without renal failure)

• Chemotherapy:
  • Mephalan + Prednisolone X 6 wk pulses
  • If cytopenic: IV cyclophosphamide weekly
  • Fail/relapse: VAD (Vincristine, Adriamycin, Dexamethasone)
  • Newer drugs: Thalidomide, Lenalidomide, Bortezomib

b. Solitary plasmacytoma: Radiotherapy <45 Gy; F/U with SPEP, IEP and UPEP

c. Extramedullary plasmacytoma: Radiotherapy

d. Asymptomatic/Smoldering multiple myeloma:

• Low risk features: Follow Up
• High risk features: Follow Up by Observation vs Chemotherapy

e. MGUS: Follow up with SPEP in 6 months and then yearly

f. Waldenstorm’s macroglobulinemia:

• Oral alkylating agents
• Newer therapies: Nucleoside analogs (fludarabine, cladribine), monoclonal antibodies (anti-CD20), thalidomide
• High dose chemotherapy followed by stem cell transplant for younger patients