Multiple Myeloma

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Multiple Myeloma

• Definition
• B-cell malignancy characterised by
  abnormal proliferation of plasma cells able to
  produce a monoclonal immunoglobulin (M protein)
  
• Incidence
• 3 - 9 cases per 100000 population / year
• more frequent in elderly
• modest male predominance

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Multiple myeloma
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Multiple Myeloma

• Clinical forms
• multiple myeloma
• solitary plasmacytoma
• plasma cell leukemia
• M protein
• - is seen in 99 of cases in serum and/or urine
• IgG gt 50, IgA 20-25, IgE i IgD 1-3
• light chain 20
• - 1 of cases are nonsecretory

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Multiple Myeloma

• Clinical manifestations are related to malignant
• behavior of plasma cells and abnormalities
  produced by M protein
• plasma cell proliferation
• multiple osteolytic bone lesions
• hypercalcemia
• bone marrow suppression ( pancytopenia )
• monoclonal M protein
• decreased level of normal immunoglobulins
• hyperviscosity

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Multiple Myeloma
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Multiple Myeloma

• Clinical symptoms
• bone pains, pathologic fractures
• weakness and fatigue
• serious infection
• renal failure
• bleeding diathesis

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Multiple Myeloma

• Laboratory tests
• ESR gt 100
• anaemia, thrombocytopenia
• rouleaux in peripheral blood smears
• marrow plasmacytosis gt 10 -15
• hyperproteinemia
• hypercalcemia
• proteinuria
• azotemia

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Diagnostic Criteria for Multiple Myeloma

• Major criteria
• I. Plasmacytoma on tissue biopsy
• II. Bone marrow plasma cell gt 30
• III. Monoclonal M spike on electrophoresis IgG gt
  3,5g/dl,
• IgA gt 2g/dl, light chain gt 1g/dl in 24h urine
  sample
• Minor criteria
• a. Bone marrow plasma cells 10-30
• b. M spike but less than above
• c. Lytic bone lesions
• d. Normal IgM lt 50mg, IgA lt 100mg, IgG lt 600mg/dl

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Multiple Myeloma
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Diagnostic Criteria for Multiple Myeloma

• Diagnosis
• I b, I c, I d
• II b, II c, II d
• III a, III c, I II d
• a b c, a b d

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Staging of Multiple Myeloma

• Clinical staging (Salmon-Durie)
• is based on level of haemoglobin, serum calcium,
  immunoglobulins and presence or not of lytic bone
  lesions
• correlates with myeloma burden and prognosis
• I. Low tumor mass
• II. Intermediate tumor mass
• III. High tumor mass
• subclassification
• A - creatinine lt 2mg/dl
• B - creatinine gt 2mg/dl

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Multiple myeloma

• MGUS monoclonal gammapathy of undetermined
  significance
• Smoldering multiple myeloma
• Symptomatic multiple myeloma

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Monoclonal gammopathy of undetermined
significance ( MGUS)

• M protein present, stable
• levels of M protein IgG lt 3,0g IgA lt 2g
  LClt1g/day
• normal immunoglobulins - normal levels
• marrow plasmacytosis lt 10
• complete blood count - normal
• no lytic bone lesions
• no signs of disease

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Smoldering multiple myeloma

• M protein present, stable
• levels of M protein IgG ? 3,0g IgA ? 2g LC ?
  1g/day
• normal immunoglobulins - normal levels
• marrow plasmacytosis ? 10
• complete blood count - normal
• no lytic bone lesions
• no signs of disease

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Diagnostic Criteria for Multiple Myeloma

• Plasma cell 10 in the bone marrow or tissue
  biopsy
• Monoclonal protein ? 3g/dl in the serum or urine
  (gt1g/dl)
• Presence of end-organ damage
• Hypercalcemia
• Ca gt 2,75 mmol/l
• Renal insufficiency
• Creatinine gt 173 mmol/l
• Anemia
• Hb lt 10g/dl
• Bone lesions
• Lytic lesions or osteopenia with compression
  fractures
• Other
• Symptomatic hyperviscosity, amyloidosis,
  recurrent bacterial infection (gt 2 episodes in 12
  months)

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Multiple Myeloma

• Poor prognosis factors
• beta-2 microglobulin gt 3,5 mg/l
• albumin gt 3,5 g/dl
• cytogenetical abnormalities 13q del t(4,14)

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Treatment of Multiple Myeloma

• Conventional chemotherapy
• High dose therapy and autologous hematopoietic
  stem cell transplantation
• Reduced intensity conditioning with allogeneic
  stem cell transplantation

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Treatment of Multiple Myeloma

• Patients lt 65 - 70 years
• high-dose therapy with autologous stem cell
  transplantation
• allogeneic stem cell transplantation
  (conventional and mini)
• Patients gt 65 - 70 years
• conventional chemotherapy

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Treatment of Multiple Myeloma

• Conventional Treatment
• Talidomide Dexamethasone
• VAD (Vincristin, Adriamycin, Dexamethasone)
• Melphlan Prednisone
• M2 (Vincristine, Melphalan, Cyclophosphamid,
  BCNU, Prednisone)
• D (Dexamethasone)
• Response rate 50-60 patients
• Long term survival 5-10 patients

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Treatment of Multiple Myeloma

• Autologous transplantation (tandem)
• patients lt 65-70 years
• treatment related mortality lt 5 -10
• response rate 80
• long term survival 20-40
• Conventional allogeneic transplantation
• patients lt 45-50 years with HLA-identical donor
• treatment related mortality 40-50
• long term survival 20-30

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Treatment of Multiple Myeloma

• Event-free and overall survival times of 515
  patients receiving autotransplants and a median
  follow-up of at least 5 years.

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Treatment of Multiple Myeloma

• Novel method
• Non-myeloablative therapy and allogeneic
  transplantation
• Tandem transplants
• Bortesomib (proteasome inhibitor)
• Lenalidomid
• Arsenic trioxide
• Statins

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Treatment of Multiple Myeloma

• Supportive treatment
• biphosphonates, calcitonin
• recombinant erythropoietin
• immunoglobulins
• plasma exchange
• radiation therapy

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Disorder Associated with Monoclonal Protein

• Neoplastic cell proliferation
• multiple myeloma
• solitary plasmacytoma
• Waldenstrom macroglobulinemia
• heavy chain disease
• primary amyloidosis
• Undetermined significance
• monoclonal gammopathy of undetermined
  significance (MGUS)
• Transient M protein
• viral infection
• post-valve replacement
• Malignacy
• bowel cancer, breast cancer
• Immune dysregulation
• AIDS, old age
• Chronic inflamation

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Monoclonal gammopathy of undetermined
significance ( MGUS)

• M protein
• 3 of people gt 70 years
• 15 of people gt 90 years
• MGUS is diagnosed in 67 of patients with an M
  protein
• 10 of patients with MGUS develop multiple myeloma