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

4. 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

6. Pathogenesis

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

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

9. Incidence

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

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

12. 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

13. Rouleaux

14. SPEP

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

20. Natural history

21. Morphology

22. Immunophenotype CD79a CD 138 CD38 CD56

23. ISS staging

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

26. Conventional cytogenetics

27. FISH

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

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

32. Calvarium

33. Skeletal survey

34. PET imaging

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

37. 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

38. Revlimid: lenalinomide

39. Revlimid: maintenance

40. Velcade: bortezomib

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

43. 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

44. 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

45. Plasma cell leukemia (PCL) Rare: SEER data (1973-2004) 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

46. 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

47. Amyloidosis

48. Thank you! email: sfanning@ghs.org