Multiple Myeloma

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Multiple Myeloma

• Natasha Walzer, M.D.
• January 25, 2006
• Morning Report

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Introduction

• Neoplastic proliferation of a single clone of
  plasma cells producing a monoclonal
  immunoglobulin
• The clone proliferates in the bone marrow
• Skeletal destruction with osteolytic lesions,
  osteopenia, and fractures

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Epidemiology

• 1 of all malignant Disease
• gt10 of all hematologic malignancies
• Annual incidence of 4/100,000
• Slightly more frequent in men than women
• Median age at Diagnosis is 66 yrs.
• 5, 10, and 20 year survivals
• 31, 10, and 4 respectively

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Clinical Manifestations

• Complaints
• Bone pain (back or chest) 60
• Weakness, Fatigue (anemia) - 32
• Weight Loss 24
• Physical Findings
• Pallor Most common
• Hepatomegaly, Splenomegaly, and Lymphadenopathy
  Uncommon findings

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Complications

• Radiculopathy
• Spinal Cord Compression
• 2 to Vertebral Fx or Plasmacytoma
• Infection
• Suppression of nml plasma cell function
• Strep Pneumoniae and Gram Negative
• Amyloidosis
• More common in Light Chain MM

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Bone Disease

• Lytic Lesions 60
• Osteoporosis, Fx, Compression Fx 20
• Myeloma Cells Produce Cytokines that
• Stimulate Osteoclastic Activity
• Inhibit Osteoblastic Activity
• Can be Detected by Plain Xray

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Renal Disease

• Serum Cr Elevated in 50 and gt2 in 20 at
  Diagnosis
• Cast Nephropathy (Myeloma Kidney)
• Large, Waxy Casts in Distal Tubules composed of
  Precipitated Light Chains
• Not detected on Dipstick
• SSA Test Positive detected as the degree of
  turbidity when SSA added to urine suggests
  presence of non-albumin proteins
• Hypercalcemia
• Amyloidosis

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Initial Work-up

• CBC w/diff peripheral smear
• Normocytic, Normochromic Anemia most common
• Rouleaux Formation gt50 of patients
• Chemistry (ca, alb, cr, LD, CRP, B2M)
• SPEP Monoclonal Protein
• Serum Viscosity (if M-protein conc. Is high,
  gt5g/dL) or sx of hyperviscosity are present
• UA and UPEP
• Metastatic bone Survey
• Bone Marrow Biopsy

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Rouleaux formation
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Diagnostic Criteria

• Presence of an M-Protein in serum and/or urine
• Presence of clonal bone marrow plasma cells or
  plasmacytoma
• Presence of Related Organ/Tissue involvement
• Hypercalcemia, renal insufficiency, anemia, lytic
  bone lesions

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International Staging System

• Stage I B2M lt3.5 mg/L and serum alb 3.5 g/dL
• Stage II neither stage I nor Stage III
• Stage III B2M 5.5 mg/L

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Bone Marrow Aspirate

• Usually gt10 plasma Cells, but can be from 5-100
  
• 50 involvement worse prognosis
• Immunoperoxidase staining detects either kappa or
  lambda light chains, NOT both (confirming
  proliferation is monoclonal)
• Immunophenotyping Malignant Plasma Cells stain
  positive for CD38, CD56, and CD138

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Bone Marrow Biopsy
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Prognostic Factors

• Performance status 3 0r 4
• Serum albumin lt 3 g/dL
• Serum Cr 2.0 mg/dL
• Platelet Count lt150,000
• Age 70 years
• Beta-2-microglobulin gt4 mg/L
• Serum Calcium 11 mg/dL
• Hemoglobin lt10 g/dL

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Treatment

• Melphalan and Prednisone (Oral)
• Preferred Tx in pts NOT going for BMT
• 7 day course repeated q 6weeks (x 3)
• Objective response in 50-60, MS of 2-3 yrs
• Melphalan, prednisone, and Thalidomide
• RR of 93 with 26 CR
• When compared to above regimen, had better CR and
  RR however, more toxicity
• Thalidomide with or w/o Dexamethasone
• Preferred in Candidates for BMT
• For pts with Relapsed or Resistent Disease
• VAD (Vincristine, Dex, and Adriamycin)
• Radiation Reserved for pts with focal process
  that has not responded to chemo

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Treatment Outcomes

• Cure Not yet been Achieved
• Molecular Complete Response
• No evidence of Disease
• Complete Response
• No detectable M protein AND nml of Plasma cells
  in Bone Marrow
• Progressive Disease
• gt25 increase in M Protein, new bony lesions, or
  a new plasmacytoma

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MGUS

• Monoclonal protein is Present
• Serum M Protein lt3 gm/dL
• Bone Marrow Plasma Cells lt10
• Absence of Anemia, Renal failure, Hypercalcemia,
  Lytic Bone Lesions
• 16 of pts will progress to MM
• Managed with Observation Only

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Asymptomatic Multiple Myeloma

• Smoldering Multiple Myeloma
• M protein gt 3gm/dl, BM Plasma Cells 10
• Absence of Complications (anemia, renal failure,
  etc)
• Observation until Disease Progression
• Indolent Multiple Myeloma
• Stable serum/urine M protein
• Bone marrow plasmacytosis
• Mild anemia, or few lytic lesions
• Observation until Disease Progression

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