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

multiple myeloma features

  • 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

multiple myeloma 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:

myeloma 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

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