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What is Multiple Myeloma?

  • Hematological Cancer
  • Develops in the bone marrow
  • Cancer of PLASMA CELLS

Monoclonal Gammopathies

Group of diseases characterized by expansion of a single clone of plasma cells

  • MGUS
  • Smoldering multiple myeloma
  • Waldenstrom's Macroglobulinemia
  • Solitary Plasmacytoma
  • AL amyloidosis
  • POEMS
  • Multiple Myelom

Epidemiology of MM

  • Incidence of 4-5/100,000
  • 1% of all cancers
  • 10% of hematologic malignancies in the US
  • Median age at diagnosis: 66
  • Risk factors
    • advanced age
    • black race
    • Males
    • family history

Clinical Aspects of Multiple Myeloma

  • Pathophysiology
    • Hypercalcemia
      • due to bone lytic lesions
      • neurological symptoms
    • Renal insufficiency
      • tubular damage by free light chains
    • Anemia
      • overgrowth of plasma cells leads to crowding out of cells for RBC production
    • Bone lesions
      • fractures due to lytic lesions caused by plasma
  • Natural Course
    • Fatal without treatment
    • Incurable, but highly effective treatments available
    • Patients generally relapse after treatment
    • Patients can undergo multiple treatments
    • Need to constantly monitor disease to detect relapse

Tests Vital to Diagnosis/Monitoring of MM

  • Clinical examination/history
  • Imaging
    • X-ray
    • CT
    • MRI
    • PET scan
  • Pathology
    • bone marrow aspirate/biopsy
  • Laboratory Tests
    • hematologic
    • chemistry
      • calcium
      • creatinine
    • serum protein electrophoresis/immunofixation
    • urine protein
    • electrophoresis/immunofixation
    • serum free light chains

International Myeloma Working Group (IMWG)

  • Offshoot of International Myeloma Foundation
  • International consortium of > 200 leading myeloma researchers
  • Develop guidelines for diagnosis, management, response criteria, etc
  • Constantly evolving and updated
  • Last update for diagnostic criteria issued 2014

2014 IMWG criteria for the Diagnosis of MM

  • Clonal bone marrow plasma cells ≥ 10% or biopsy proven bony or soft tissue plasmacytoma (clonality must be established by flow, IHC, or IF)

PLUS

  • Presence of related organ or tissue impairment (CRAB)

OR

  • Presence of a biomarker associated with near inevitable progression to end-organ damage

*Rajkumar et al. Lancet Oncol 2014;15:e538-48.

Presence of related organ or tissue impairment (CRAB)

  • Anemia
    • hemoglobin < 10g/dL or
    • 2g/dL below normal
  • Hypercalcemia
    • serum calcium > 11 mg/dL
  • Renal insufficiency
    • eGFR/GFR < 40 ml/min OR
    • serum creatinine > 2mg/dL
  • Bone lesions
    • one or more osteolytic lesions on skeletal radiography, MRI, CT or PET/CT

Presence of a biomarker associated with near inevitable progression to end-organ damage: Myeloma Defining Events (MDE's)

  1. ≥ 60% clonal plasma cells in bone marrow
  2. involved/uninvolved FLC ratio of 100 or more (involved FLC must be ≥ 100 mg/L)
  3. MRI with more than one focal lesion (involving bone or bone marrow)

*Rajkumar et al. Lancet Oncol 2014;15:e538-48.

Other Monoclonal Gammopathies/Plasma Cell Disorders

  • Smoldering Multiple Myeloma
  • Monoclonal Gammopathy of Undetermined Significance (MGUS)
  • Solitary Plasmacytoma
  • POEMS Syndrome
  • Light Chain Amyloidosis