Multiple Myeloma

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Multiple Myeloma

• G.A.Prasad MD
• 4/5/99

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Plasma Cell Disorders

• Monoclonal neoplasms Development from common
  progenitors in the B lymphocyte lineage
• Serum Electrophoresispermits determination of
  the amount of immunoglobulins in the serum.
• Normal Igs form a broad peak in the Gamma
  region.
• Plasma cell Tumors Sharp spike in the Gamma
  region M spike ( Monoclonal) gt 5g/L.
• Confirmation with Immunoelectrophoresis.

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Conditions associated with M proteins

• Stable production
• Monoclonal gammopathy of undetermined
  significance
• Smouldering multiple myeloma
• Progressive production
• Multiple myeloma (IgG, IgA, free light chains,
  IgD, IgE)
• Plasma cell leukaemia Solitary plasmacytoma
  of bone
• Extramedullary plasmacytoma
• Waldenström's macroglobulinaemia (IgM)
• Chronic lymphocytic leukaemia Malignant
  lymphoma
• Primary amyloidosis Heavy chain disease
• Non neoplastic conditions Cirrhosis,Sarcoid,Ca
  Colon/Breast

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M protein

• Amount of the M protein -marker of tumor load
• Nature variable
• May be an intact molecule or a fragment
• Extramedullary / Solitary plasmacytomas lt1/3
  have M spike
• 20 of Myelomas _ only Light Chains produced
• Non Secretory Myelomas_rare
• frequency of myelomas Ig Ggt IgA gt IgD

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1.Normal Plasma 2.Polyclonal Hyperglobulinemia
3.Monoclonal Spike4.Bence Jones proteins in urine
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Multiple Myeloma

• Definition Malignant proliferation of plasma
  cells derived from a single clone
• Etiology radiationmutations in oncogenes
  familial causesrole of IL 6
• Incidence/Prevalence 14,400 cases in 1996
  incidence 30/1,00,000
• Incidence increases with age
• Malesgt females Blacks gt Whites

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Clinical Manifestations

• Common
• bone pain and pathological fractures
• anemia and bone marrow failure
• infection due to immune-paresis and neutropenia
• renal impairment
• Less common
• acute hypercalcemia
• symptomatic hyperviscosity
• neuropathy
• amyloidosis
• coagulopathy

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Clinical Manifestations

• Bone Pain
• 70,Precipitated by movement
• Pathological fractures
• Activation of Osteoclasts by OAF produced by
  myeloma cells
• Susceptibility to infections
• Diffuse hypogammaglob. If the M spike is excluded
• Poor Antibody responses ,Neutrophil dysfunction
• Pneumococcus,S.aureus,GN aerobes-Pneumonia,Pyelone
  phrits

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Clinical Manifestations

• Renal failure 25
• Multiple contributory factors
• Hypercalcemia,Hyperuricemia,recuurent Infections
• Tubular damage produced by Light chains
• type 2 proximal RTA,Non selective proteinuria
• Anemia 80
• Normochromic/Normocytic
• MyelophthisisInhibition by cytokines produced by
  plasma cells.
• Leukopenia/thrombocytopenia only in advanced
  cases.

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Plasma Cell
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Minimal diagnostic criteria for myeloma

• gt10 Plasma cells in bone marrow or plasmacytoma
  on biopsy
• Clinical features of myeloma
• Plus at least one of
• Serum M band (IgG gt30 g/l IgA gt20 g/l)
• Urine M band (Bence Jones proteinuria)
• Osteolytic lesions on skeletal survey

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Bone Marrow Aspirate
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Lytic lesions(Punched out lesions) on X Ray.
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Vertebral collapse secondary to
osteoporosis/pathological fracture
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MGUS Definition

• No explained symptoms suggestive of myeloma
• Serum M protein concentration lt 30 g/l
• lt 5 percent plasma cells in bone marrow
• Little or no M protein in urine
• No bone lesions
• No anemia, hypercalcemia, or renal impairment
• M protein concentration and other results stable
  on prolonged observation

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Staging 1.

• Hb/Serum Ca/M component level/radiology
• Stage I Hb gt10Serum Ca lt 12Normal Bone
  surveyLow M component levels
• Stage III HB lt 8.5, Serum Ca gt12Lytic
  lesionsHigh M component levels
• Stage II Intermediate
• Divided into A or B depending on Serum Creatinine
  level lt or gt than 2 mg/dl.

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Staging 2

• Serum b2 microglobulin levels.
• If lt 0.004 g/L Stage 1 Median survival 43
  months
• If gt0.004 g/L Stage II Median survival 12 months

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Treatment

• Options
• melphalan with or without prednisone
• Infusional chemotherapy - vincristine and
  adriamycin infusion plus either dexamethasone all
  methylprednisolone
• combination therapy - for example, adriamycin,
  carmustine, cyclophosphamide, and melphalan
• weekly cyclophosphamide (C weekly)

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Treatment

• Prompt reduction in bone pain,anemia,hypercalcemia
  .
• M component lags behind -4-6 weeks to fall
• 60 of patients will acieve a 75 reduction in
  tumor mass.
• Treat q 4-6 weeks for 1-2 years.
• Leads to a plateau phase- relapse within a year.
• Maintenance alpha Interferon ???

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Treatment

• Supportive therapy
• analgesia
• rehydration
• treatment and any hypercalcemia
• treatment of any renal impairment
• treatment of any infection
• local radiotherapy if required
• chemotherapy
• prevention of further bone damage