David Siegel, MD, PhD

1. David Siegel, MD, PhD Hackensack University Hackensack, New Jersey

2. Conventional Chemotherapy (CC) vs ASCT Randomized Studies No.of pts 200 401 194 190 164 516 CRrate 5 vs 22** 8 vs 44** 6 vs 25** - 11 vs 30** 15 vs 17 MedianEFS 18 vs 28** 19 vs 31** 16 vs 28** 19 vs 25** 34 vs 42 21 vs 25 MedianOS 44 vs 57** 42 vs 54** 42 vs 58+** 45 vs 42 67 vs 65 53 vs 62 Age  65  65 50-70 55-65  65 - IFM90(N Engl J Med 96) MRC7(N Engl J Med 03) Italian MMSG(Blood 04) MAG 91(ASH 99) PETHEMA*(ASH 03) US Intergroup(ASH 04) CR=Complete Response EFS=Event-Free Survival OS=Overall Survival * Only in patients responding to initial CC ** Statistically significant Harousseau et al, Best Prac Res Clin Haematol. 2005;83-18

3. Age Not Important for Clinical Outcome on Multivariate Analysis • EFS P OS P Favorable cytogenics .004 Favorable cytogenics .009 ≤ 12 mo prior therapy .01 B2M ≤ 2.5 mg/L .03 B2M ≤ 2.5 mg/L .01 ≤ 12 mo prior therapy .4 Age < 65 yr .2 Age < 65 yr .8 EFS=Event-Free Survival OS=Overall Survival Siegel et al, Blood.1999; 9351-54

4. Event-Free Survival 1.0 Age N < 65 49 ≥ 65 49 0.8 0.6 Median =2.8 yrs Proportion 0.4 Median =1.5 yrs 0.2 p = .2 0 1 2 3 4 5 6 Years from first transplant Siegel et al, Blood.1999; 9351-54

5. Overall Survival 1.0 Age N < 65 49 ≥ 65 49 Median = 4.8 yrs 0.8 0.6 Proportion Median =3.3 yrs 0.4 0.2 p = .4 0 1 2 3 4 5 6 Years from first transplant Siegel et al, Blood.1999; 9351-54

6. AggregateOS EFS,andCR DurationforPatients n=ReceivingAuto-SCT Over the Age of 70 Years* 1 Median (months) EFS 15 OS 24 CR duration 18 Probability 0.5 0 0 2 24 36 48 60 72 Months from first auto-SCT CR=Complete Response, EFS=Event-Free Survival, OS=Overall Survival * Median age was 72 years. Badros et al, BritishJournalofHaematology.-

7. What type of induction therapy would be best for this particular patient ? • Induction with high-dose pulse dexamethasone • (40 mg/m2 given on Days 1-4, 9-12, and 17-20 every 35 days)

8. What type of induction therapy would be best in a patient with more significant consequences of diabetes at baseline? • Weekly dexamethasone plus thalidomide in place of high-dose pulse dexamethasone at the outset • OR • Regimen combining dexamethasone with bortezomib

9. Recommendations • High-dose pulse dexamethasone for no more than 2 cycles • Stem cell harvest and ASCT • G-CSF, without cyclophosphamide • MEL-200 and proceed to autologous stem cell transplantation

10. Maintenance Therapy Following ASCT • No study in myeloma has yet shown a survival advantage

11. Pamidronate With or Without Thalidomide as Maintenance Therapy after Tandem Transplants • Longer progression-free survival (PFS) with addition of thalidomide • Significant benefits only in patients with • ≥ 90% response at randomization (P = .05) • Either deletion of chromosome 13 or B2M > 3 mg/L (P < .002) • Longer event-free survival • Overall survival similar in all 3 groups Attal M, et al. ASH 2004. Abstract 535.