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:

and

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

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

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:

6. Other: Peripheral neuropathy, Myelomatous meningitis

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

International Myeloma working group Diagnostic criteria: ≥2 of –

1. Asymptomatic:

2. Symptomatic: + ≥1 of CRAB

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)

Durie Salmon staging mnemonic: ABCdE

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:

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