2. UNDERSTANDING MYELOMA Brian G.M. Durie, M.D. Chairman International Myeloma Foundation

3. Most Common Initial Problems Bone pain Bone pain Anemia/Fatigue Anemia/Fatigue NO Problems: Incidental finding during routine exam NO Problems: Incidental finding during routine exam Kidney problem Kidney problem Other Other

4. Diagnosis Bone Marrow Imaging Electro- pheresis

5. Bone Lesions In Myeloma Lytic lesions LEGELBOW

7. Staging Single lesion Single lesion  Solitary plasmacytoma  Stage I Multiple lesions Multiple lesions  Stages II / III A/B A – Creatinine < 2mg /DL B – Creatinine > 2mg/DL

8. SOLITARY PLASMACYTOMA T1-wt MRISTIR – wt MRI Sagittal CT Sagittal FDG PET

9. STAGING WITH FDG PET FL on PET & MRI: Multiple Myeloma FDG PET: Severe Diffuse (D) and Focal (F) DiseaseD D D D D F F F F D MRI – STIR weighted of thoracic spine FDG PET scan of thoracic spine

10. Pretreatment 3 months later Confirmation of Remission Plasmacytomas

14. MYELOMA PROTEIN “SPIKE” Low AlbuminSpike

15. International Staging System  2 M / S. Alb Stage 1 Low  2 M < 3.5* plus S. Albumin** > 3.5 G/DL Stage 2  2 M < 3.5 but albumin < 3.5 Or  2 M or higher: 3.5 – < 5.5 Stage 3 High  2 M > 5.5mg/DL * mg/DL ** Gm/DL

16. Other Factors Impact of AGE Impact of AGE C-Reactive Protein (CRP) C-Reactive Protein (CRP) LDH LDH Chromosome 13 Chromosome 13  Cytogenetic deletion  FISH analysis Micro array classification Micro array classification

17. Genetic Studies in Myeloma Gene Array: Normal vs MM MM +/- Bone Disease Sky Karyotype No Lytic Lesions> 3 Lytic Lesions Normal Bone Marrow Cells Clonally restricted PC w/o Chromosome 13 deletion Clonally restricted PC w / Chr. 13 deletion D13S31 D10S2142 anti-kappa NPCMM High Gene Expression Low 120 genes NL Myeloma CA13 – Tri-FISH DKK1, FRZB, CENPA, TYMS, TTK, MAD2L1, PCNA, PRKDC, CCNF, AML1B WNT10B, ARHE, LNHR, SLAM, TACI, PIM1, IL6R, BIK, BAX, CFLAR

18. Starting Treatment Supportive Measures – for pain, anemia, infection … Supportive Measures – for pain, anemia, infection … Systemic Therapy – oral and/or I.V. treatment Systemic Therapy – oral and/or I.V. treatment

19. Supportive Care Bone – Aredia or Zometa Bone – Aredia or Zometa Anemia – EPOProcrit/Epogen Anemia – EPOProcrit/Epogen Other – radiation, antibiotics, fluids, pain, medication … Other – radiation, antibiotics, fluids, pain, medication …

20. First Therapy Induction or Frontline Saving Stem Cells Saving Stem Cells  VAD  DEX  Thalidomide/Dexamethasone  Cytoxan NOT Saving Stem Cells NOT Saving Stem Cells  M/P  Other combos

21. Next Steps Harvesting Harvesting “Consolidation” “Consolidation”  Auto stem cell transplant  “Mini-allo” Maintenance Maintenance

22. Clear Recommendation Required

23. Mutual Agreement is Essential

24. MENTAL HEALTH Stress reduction Stress reduction Confidence in treatment plan Confidence in treatment plan Expectation of remission Expectation of remission Future plans Future plans HOPE HOPE

25. YOUR DOCTOR Informed Informed Cooperative Cooperative Open to discussing options Open to discussing options Caring for YOU Caring for YOU

26. Caring and Trust are Crucial

27. Help Others When You Can