Multiple Myeloma March 13, 2012 Suzanne R. Fanning, DO Greenville Health System

Definition Neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin Spectrum of plasma cell dyscrasia: MGUS – monoclonal gammopathy of undetermined significance Smoldering MM (MM = multiple myeloma) Active MM

Pathogenesis

Epidemiology 1% of all cancer (rare) 10% of hematologic malignancies

Incidence 4-5/100,000 Race: black 2-3x > caucasian Gender: male > female (1.4:1) Median age: 66 <50: 10% <40: 2%

Incidence

Risk factors 1 st degree relative: 3.7x Increasing age MGUS – disease spectrum

Presentation Bone pain – 58% Anemia – 73% (macrocytic) Hypercalcemia – 28% Renal dysfunction – 48% ARF (Cr>2.0) – 20% Infection Radiculopathy

Labs CBC w/ peripheral smear CMP (includes calcium, Cr, and albumin) B2-microglobulin Serum protein electopheresis w/ immunofixation 24 urine for electropheresis w/ immunofixation Free light chains Quantitative immunoglobulins

Rouleaux

SPEP

Diagnosis: Active MM >10% aberrant plasma cells in marrow Presence of serum or urine monoclonal protein M protein End organ damage

Natural history

Morphology

Immunophenotype CD79a CD 138 CD38 CD56

ISS staging

Risk stratification Requires: Conventional cytogenetics FISH for myeloma panel Based on these results determine: Favorable Intermediate High-risk

Conventional cytogenetics

FISH

Solitary plasmacytoma SBP: bone SEP: extramedullary Most common location = sinus Treatment is localized – radiation Increased risk of transition to active MM

Imaging Skeletal survey Standard of care MRI compression fracture cord compression PET scan

Calvarium

Skeletal survey

PET imaging

Treatment Induction chemotherapy Consolidation w/ autologous stem cell transplant or Stem cell harvest w/ cryopreservation Maintenance

Revlimid: lenalinomide Acts as a multi-targeted agent: Immunomodulatory Helps the body heal itself Induces apoptosis Anti-angiogenic Works against the blood vessel formation to feed the tumor cells

Revlimid: lenalinomide

Revlimid: maintenance

Velcade: bortezomib

Induction chemotherapy RVD (revlimid, velcade, decadron) CyBorD (cytoxan, bortezomib, decadron) Rd (rev/dex) Vd (velcade/dex)

Autologous transplant Average PFS: 5-7yrs for standard risk disease High dose chemo: melphelan 200mg/m2 TRM: 1-3% Requires RBC and platelet transfusional support Requires prophylactic antibiotics Monitor for fever/infection

Relapse Revlimid or Velcade – depending on timing of last dose Carfilzomib Pomalinomide (a new version of Revlamid) Cytoxan/prednisone VDD (velcade, doxil, dex) Autologous stem cell transplant

Plasma cell leukemia (PCL) Rare: SEER data ( ) 49,000 cases of MM 0.6% PCL Median age: 55 (younger age, for this disease) 2° PCL: occurs as progression in ¼ cases of MM Induction more intense: VTD-PACE Poor prognosis

Amyloidosis Aberrant immunoglobulin deposition in tissues Complicates 10% of cases of MM Diagnosis: fat pad biopsy Look at tissues under a microscope Congo stain: apple-red bifringence

Amyloidosis

Thank you!