See also Monoclonal Gammopathies

I. Epidemiology and pathophysiology
  1. A malignancy of plasma cells;the most common primary cancer of bone
  2. As of 2010, 5-year survival is 68%and 10y survival is 55.3%  in pts diagnosed at < 45yo; lower in older patients
  3. Risk factors
    1. Incidence increases with age; Median age at diagnosis = 70y
    2. Men > women
    3. African ancestry is a risk factor (RR about 2 compared with individuals of European ancestry); Rare in Asians
    4. Rheumatoid arthritis
    5. Obesity
    6. Exposure to ionizing radiation
    7. Benzene exposure
    8. Certain pesticides

II. Clinical and laboratory features
  1. "M" protein spike on serum and urine protein electrophoresis
    1. Present in SPEP and UPEP in 82% and 75% of patients with MM, respectively
    2. Immunofixation and free light chain assay can increase sensitivity
    3. 1-2% of MM patients have "nonsecretory" myeloma that does not produce a spike.
    4. Not 100% specific-Can have an "M" spike without MM, e.g. monoclonal gammopathy of undetermined significance ("MGUS"), which is generally considered to be a premalignant condition and converts to myeloma at about 1%/yr
  2. Classification
    1. Monoclonal Gammopathy of Uncertain Significance (see above) = "M" protein < 3g/dL, < 10% clonal plasma cells in bone marrow, and no end-organ damage
    2. "Asymptomatic" MM = "M" protein of 3g/dL or greater, 10% of greater clonal plasma cells in bone marrow, but no end-organ damage
    3. "Symptomatic" MM = "M" protein of 3g/dL or greater, clonal plasma cells on bone marrow biopsy, and end-organ damage
      1. 40% of patients with the latter two criteria have "M" protein of < 3g/dL; 20% will have < 1g/dL
      2. 5% of patients with the first and last criteria have < 10% clonal plasma cells on bone marrow biopsy
  3. End-organ damage in MM-"CRAB" mnemonic (calcium, renal, anemia, bone)
    1. Hypercalcemia (usually > 1mg/dL over normal)-Present in 15-20% of pts at time of diagnosis
    2. Renal impairment (serum Cr usually > 2.0g/dL), resulting from light chain deposition in kidney
    3. Anemia (Hb > 2g/dL below lower limit of normal)-Seen in about 65% of patients; typically normocytic and normochromic
    4. Bone involvement: Lytic lesions, osteoporosis, and fracture-Seen on 80% of pts at time of diagnosis
    5. Other clinical manifestations: Hyperviscosity syndrome, systemic amyloidosis, recurrent bacterial infections
II. Management
  1. Treatment generally considered to be indicated only for symptomatic MM, not asymptomatic MM or MGUS
  2. Treatment for symptomatic MM
    1. If < 65yo, autologous stem cell transplantation is considered treatment of choice (median survival 68mos)
    2. Alternatives include (prednisone + melphalan) +/- thalidomide
    3. Relapse after treamtent is common and is sometimes treated with (bortezomib, thalidomide, and lenalidomide)
  3. For patients with asymtpomatic MM or MGUS
    1. Teatment may not improve outcomes and may increase risk for acute leukemia
    2. Should check renal function and serum calcium Q3-4mos
III. Waldenstrom's macroglobulinemia
  1. Caused by uncontrolled proliferation of lymphocytes and plasma cells, which produce IgM proteins with kappa light chains
  2. Mean age at diagnosis is 65 years. 
  3. Clinical features:
    1. Symptoms: Weakness, fatigue, weight loss, bleeding, and recurrent infections
    2. Px: Pallor, hepatosplenomegaly, and lymphadenopathy.
    3. Lab: Moderate anemia and monoclonal IgM peaks on serum electrophoresis. Bence-Jones protein seen in 80% of cases in contrast with MGUS where it is typically absent
    4. Lytic bone lesions not seen (in constrast to multiple myeloma)
    5. Bone marrow biopsy reveals mostly lymphocytes
(Sources include Core Content Review of Family Medicine, 2012)