1. Revlimid ® (lenalidomide), Melphalan and Prednisone (R-MP) Gimema: Italian Myeloma Network Antonio Palumbo Dept. Hematology, University of Torino Multicenter Phase I/II Trial Newly Diagnosed Patients Newly Diagnosed Patients Age >65 Years

2. Disclosures for (Antonio Palumbo, M.D.) N/A = Not Applicable (no conflicts listed) Presentation includes discussion of the following off-label use of a drug or medical device. Celgene. Pharmion. Scientific Advisory Board Celgene, Pharmion. Speakers’ Bureau (N/A for no conflict or name of company) Major Stockholder Celgene, Pharmion. Consultant (N/A for no conflict or name of company) Employee Research Support/P.I. In compliance with ACCME policy, the ASCO requires the following disclosures to the activity audience:

3. Rationale 54% MP 5.0 DEX 12.2 DEX MPTDiagnosis (3) P<0.00115.1EFS (months) REV-DEXRelapse (2) P<0.001*21.1EFS (months) 27% MP P=0.0006EFS @ 2 years Diagnosis (1) *P<0.001 for pts not receiving Melphalan (1) Facon T et al. Blood. 2006;107:1292. (2) Palumbo A et al. Lancet. 2006;367:825. (3) Dimopoulos M et al. Blood. 2005;106:6a [abstract 6]

4. Dept. Hematology, University of Torino 1 2 3 4 21 Revlimid ® 5–10 mg/day, continuously until relapse Mel 0.18–0.25 mg/Kg Prednisone 2 mg/Kg Every 4–6 weeks for a maximum of 9 cycles day Melphalan mg/Kg/d Revlimid ® mg/d Patients Cohort 1 0.1856 Cohort 2 0.2556 Cohort 3 0.18106+15 Cohort 4 0.25106+15 6 patients in each cohort with additional 15 pts in cohort 3 and 4 Treatment Schedule

5. Dept. Hematology, University of Torino Patient Characteristics No. of patients53 Median age (range) 71 (57–77) 65–70 years 43% 71–75 years 51% Chromosome Deletion (13 q) 38% ß2-microglobulin mg/L (median) 3.4 Hemoglobin g/L (median) 12.0 Creatinine mg/dL (median) 1.0 Ca++ mmol/L (median) 2.41

6. Dept. Hematology, University of Torino Dose Limiting Toxicity3/61/60/60/6 Pts with DLT 1/6 Cutaneous GR 3 Thrombosis GR 4 Metabolic GR 3 2/6Delay at cycle 2 1/6Neutropenia fever 1/6 Severe Neutropenia Cohort 4 0.25–10 Cohort 3 0.18–10 Cohort 2 0.25–5 Cohort 1 0.18–5DLT at Cycle 1

7. Dept. Hematology, University of Torino Cohort 3 (0.18-10) [N=21] Cohort 4 (0.25-10) [N=20] 0102030405060 % Patients Neutropenia Thrombocytopenia Anemia G-CSF Hematologic Toxicity Grade 3–4 Adverse Events70

8. Dept. Hematology, University of Torino % Patients Cohort 3 (0.18-10) [N=21] Cohort 4 (0.25-10) [N=20] Non-Hematologic Toxicity Grade 3–4 Adverse Events

9. Dept. Hematology, University of Torino Cycle 1-2 [N=41] Cycle 5-6 [N=34] % Patients Neutropenia Thrombocytopenia Anemia Infection and neutropenic fever Cutaneous Thrombosis 010203040 Grade 3–4 Adverse Events50

10. Dept. Hematology, University of Torino Thromboembolism R-MP (n=41) MPT (n=64) MPT (n=65) Aspirin 100 mg/d Enoxaparin 40 mg/d No Prophylaxis DVT2.4%*3%18.4% Pulmonary Thromboembolis 2.4%0%4.6% Arterial Occlusion0% 1.5% Total4.8%3%24.5% *DVT occurred after aspirin discontinuation

11. Dept. Hematology, University of Torino R-MP vs MP: Response Rate After 1 cycle R-MP (N=41)After 6 cycles MP (N=126)* Historical control 17.5% 27.5% 62.5% 2.5% 0% 0 10 20 30 40 50 60 70 CRVGPRPRMRSD-PD %92.5%64.4% 31.8% 16.7% 35.7% 2.4% 0 10 20 30 40 50 60 70 CRVGPRPRMRSD-PD 9.6% % *Lancet 2006;367:825

12. Dept. Hematology, University of Torino R-MP vs MPT: Response Rate R-MP (N=41)* Median 7 cycles (2-9) MPT (N=129)*^ Historical control 81.3%100% 0% 14.6% 43.9% 24.4% 17.1% 0 5 10 15 20 25 30 35 40 45 50 CRVGPRPRMRSD-PD % 13.2% 5.4% 39.5% 20.9% 15.5% 0 5 10 15 20 25 30 35 40 45 CRVGPRPRMRSD-PD % *Best response ^Lancet 2006;367:825

13. Dept. Hematology, University of Torino R-MP: Response Rate Cohort 3 (0.18-10) [N=21]* Median 7 cycles (4-9) Cohort 4 (0.25-10) [N=20]* Median 5 cycles (2-9) 0% 14.3% 33.3% 28.5% 23.8% 0 10 20 30 40 50 60 CRVGPRPRMRSD-PD % 100%100% 0% 15% 55% 20% 10% 0 10 20 30 40 50 60 CRVGPRPRMRSD-PD % *Best response

14. Dept. Hematology, University of Torino Event-Free SurvivalR-MP MPT Historical control 87%@16 months 71%@18 months % of patients MPT: median follow-up 17.6 months (0.23-44.3) [N=129] R-MP: median follow-up 9.6 months (5.7-16.6) [N=53] months

15. Dept. Hematology, University of Torino Conclusions Early deaths 0% Grade 3/4 Adverse Events (incidence >5%) –Neutropenia66% –Thrombocytopenia34 % –Anemia17 % –Cutaneous10 % –Neutropenic Fever 8% Response Rate (median 7 cycles) –CR + VGPR 41% –CR + PR 85 % –CR + PR + MR100 %

16. Dept. Hematology, University of Torino BRESCIADr. Rossi, Dr. Crippa CATANIAProf. Giustolisi, Prof. Di Raimondo COSENZAProf. Morabito GENOVAProf. Gobbi, Dr. Canepa MILANOProf. Corradini, Dr. Montefusco PARMAProf. Rizzoli, Dr. Giuliani ROMA 1Prof. Foà, Dr. Petrucci S. G. ROTONDODr. Musto, Dr. Falcone SIENAProf. Lauria, Dr. Gozzetti TORINO 1Prof. Boccadoro, Dr. Falco We Are Grateful to all Patients, Nurses and Physicians of the Participating Centers