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

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:

Rationale 54% MP 5.0 DEX 12.2 DEX MPTDiagnosis (3) P< EFS (months) REV-DEXRelapse (2) P<0.001*21.1EFS (months) 27% MP 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]

Dept. Hematology, University of Torino 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 Cohort Cohort Cohort patients in each cohort with additional 15 pts in cohort 3 and 4 Treatment Schedule

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

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 –10 Cohort –10 Cohort –5 Cohort –5DLT at Cycle 1

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

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

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 Grade 3–4 Adverse Events50

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

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% CRVGPRPRMRSD-PD %92.5%64.4% 31.8% 16.7% 35.7% 2.4% CRVGPRPRMRSD-PD 9.6% % *Lancet 2006;367:825

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% CRVGPRPRMRSD-PD % 13.2% 5.4% 39.5% 20.9% 15.5% CRVGPRPRMRSD-PD % *Best response ^Lancet 2006;367:825

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

Dept. Hematology, University of Torino Event-Free SurvivalR-MP MPT Historical control months months % of patients MPT: median follow-up 17.6 months ( ) [N=129] R-MP: median follow-up 9.6 months ( ) [N=53] months

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 %

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