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Disclosures for Palumbo Antonio, MD Honoraria to disclose Celgene Janssen-Cilag.

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Presentazione sul tema: "Disclosures for Palumbo Antonio, MD Honoraria to disclose Celgene Janssen-Cilag."— Transcript della presentazione:

1 Disclosures for Palumbo Antonio, MD Honoraria to disclose Celgene Janssen-Cilag

2 A Phase III Study of VMPT versus VMP in newly diagnosed elderly myeloma patients Antonio Palumbo 1, Sara Bringhen 1, Davide Rossi 2, Salvatore Berretta 3, Vittorio Montefusco 4, Jacopo Peccatori 5, Monica Galli 6, Angelo Carella 7, Paola Omedè 1, Mario Boccadoro 1 1 Divisione di Ematologia dellUniversità di Torino, A.O.U. San Giovanni Battista, Torino, Italy; 2 Università del Piemonte Orientale Amedeo Avogadro, Novara, Italy; 3 Ospedale Ferrarotto, Università di Catania, Catania, Italy; 4 Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; 5 Istituto Scientifico San Raffaele, Milano, Italy; 6 Ospedali Riuniti, Bergamo, Italy; 7 A.O.U. San Martino, Genova, Italy. GIMEMA: Italian Myeloma Network

3 Rationale: 3 drug combinations 1 San Miguel JF et al. New Eng J Med 2008; 359: Palumbo et al. Blood 2008;112: V = Bortezomib; M= Melphalan; P = Prednisone; T= Thalidomide MP 1 (diagnosis) MPT 2 (diagnosis) VMP 1 (diagnosis) No. patients CR4%16%33% > VGPR8%29%41% > PR39%76%74%

4 VMPT 3 (relapse) RMPT 4 (relapse) VCRD 5 (diagnosis) No. patients CR17%13%56% > VGPR43%33%68% > PR66%76%100% 3 Palumbo et al. Blood 2007;109: Palumbo ASH 2008; 112: Kumar ASH 2008; 112: 93 V=Bortezomib; M=Melphalan; P=Prednisone; T=Thalidomide; R=Lenalidomide; C=Cyclophosphamide; D=Dexametasone Rationale: 4 drug combinations

5 Aims VMPT: superior to VMP? Weekly infusion of bortezomib: safety improvement?

6 511 patients (older than 65 years) randomized from 58 Italian centers Patients: Symptomatic disease, organ damage, measurable disease 65 yrs or <65 yrs and not transplant-eligible; creatinine 2.5 mg/dL Treatment schedule VMP Cycles 1-9 Bortezomib 1.3 mg/m 2 IV: days 1,8,15,22* Melphalan 9 mg/m 2 and prednisone 60 mg/m 2 days 1-4 VMPT Cycles 1-9 Bortezomib 1.3 mg/m 2 IV: days 1,8,15,22* Melphalan 9 mg/m 2 and prednisone 60 mg/m 2 days 1-4 Thalidomide 50 mg/day continuously RANDOMIZERANDOMIZE 9 x 5-week cycles in both arms MAINTENANCE Bortezomib 1.3 mg/m 2 IV: days 1,15 Thalidomide 50 mg/day continuously NO MAINTENANCE Until relapse * 64 VMP patients and 71 VMPT patients were treated with twice-weekly infusions of Bortezomib

7 VMPT (n=221) VMP (n=229) Age (median) 70 years 71–75 years >75 years 2-microglobulin-mg/L (median) Hemoglobin-g/dL (median) Creatinine-mg/dL (median) Calcemia-mmol/L (median) 71 49% 30% 21% % 35% 22% Patient Characteristics

8 Best Response CRVGPRPR VMPT N=221 Median No. of cycles 5 51%* % of patients SDPD 35 § 42%* % of patients CRVGPRPR § P < * P = 0.06 VMP N=229 Median No. of cycles 5 SDPD 21 §

9 Time to response % of patients Treatment cycle PRCR

10 Time to next therapy Progression free survival P = 0.30P = 0.13 % of patients Months Time to next therapyProgression free survival Median follow-up 16.1 months VMPT VMP VMPT: 36 months = 71% VMP: 36 months = 56% VMPT VMP VMPT: 36 months = 80% VMP: 36 months = 78%

11 Progression free survival Age: 75 years vs > 75 years P=0.47 VMP % of patients months Age 75 years Age >75 years All patients % of patients months P=0.02 Age 75 years Age >75 years P=0.006 VMPT % of patients months Age 75 years Age >75 years

12 Progression free survival Response rate: CR vs VGPR vs PR CR VGPR PR % of patients months % of patients months CR PR P=0.005 All patients VGPR PR P= % of patients months All patients

13 Progression free survival FISH analisis: t(4;14) or t(14;16) or del17 % of patients months All patients P=0.39 % of patients months VMP P=0.81 % of patients months VMPT P=0.25 Standard Risk High Risk Standard Risk High Risk Standard Risk High Risk

14 Progression free survival International Staging System: ISS 1 vs ISS 2-3 % of patients months All patients P=0.30 ISS 1 ISS 2-3 % of patients months VMP P=0.04 ISS 1 ISS 2-3 % of patients months VMPT P=0.45 ISS 1 ISS 2-3

15 Progression free survival FISH analisis t(4;14) or t(14;16) or del17 and ISS 2-3 % of patients months VMP Standard Risk High Risk P=0.08 months % of patients VMPT Standard Risk High Risk P=0.06 % of patients months All patients Standard Risk High Risk P=0.02

16 Grade 3-4 Hematologic Adverse Events VMP vs VMPT % of patients VMPTVMP

17 Grade 3-4 Non-hematologic Adverse Events VMP vs VMPT % of patients VMPTVMP

18 Efficacy and Toxicity bortezomib infusion schedule VMPTVMP twice weekly (N=71) weekly (N=150) twice weekly (N=64) weekly (N=165) CR38%32%27%20% Grade 3-4 Peripheral neuropathy 18%2%14%2% Dose reduction*42%11%35%13% Discontinuation*10%3%15%4% 25 VMPT and 19 VMP patients received both twice- and once-weekly *Due to peripheral neuropathy

19 Conclusion VMPT (N=177) VMP (N=177) P value CR35%21%< years71%56% years90%89%0.81 Grade 3-4 Peripheral neuropathy* 2% - Discontinuation § 3%4%- *For patients (VMPT 150; VMP 165) who received weekly infusion of bortezomib,) § Due to peripheral neuropathy

20 1. ALESSANDRIALevis, Baraldi 2. ANCONALeoni, Offidani 3. AOSTADi Vito 4. ASCOLI PICENOGalieni, Bigazzi 5. ASTIScassa, Campa 6. AVELLINOCantore, Volpe 7. AVIANOTirelli, Rupolo 8. BARIDammacco, Lauta 9. BARILiso 10. BERGAMOBarbui, Galli 11. BIELLATonso 12. Cavo, Tosi 12. BOLOGNACavo, Tosi 13. BOLZANOPescosta 14. BRAVanni, Stefani 15. BRESCIARossi, Crippa 16. CAGLIARIAngelucci, Carubelli 17. CAGLIARIMantovani 18. CAMPOBASSOStorti 19. CANDIOLOAglietta, Capaldi 20. CATANIAGiustolisi, Di Raimondo 21. CATANZAROPiro 22. CATTOLICAPasquini 23. CESENAGuardigni 24. CHIOGGIABattista 25. CIRIE'Freilone, Beggiato 26. COSENZAMorabito 27. CREMONAPassalacqua, Morandi 28. CREMONAMorandi 29. CUNEOGallamini, Grasso 30. FIRENZEBosi, Nozzoli 31. FOGGIAMonaco, Ferrandina 32. FOGGIAMonaco 33. FORLIAmadori, Gentilini 34. GALLARATECiambelli 35. GENOVAGobbi, Canepa 36. GENOVACarella 37. LATINAZapone 38. LECCEPavone 39. MATERACiancio 40. MESSINABrugiatelli, Mamone 41. MESSINAMusolino 42. MILANOCorradini, Montefusco 43. MILANOMorra 44. MILANOBregni 45. MODENANarni 46. MONTEFIASC.Montanaro, Niscola 49. MONZAPogliani, Rossini 50. NAPOLIRotoli,Catalano 51. NAPOLIFerrara 52. NOCERA INF.DArco, Califano 53. NOVARAGaidano, Rossi 54. NUOROLatte, Palmas 55. ORBASSANOSaglio, Guglielmelli 56. PADOVASemenzato, Zambello 57. PALERMO Mirto, Cangialosi 58. PARMARizzoli, Giuliani 59. PAVIALazzarino, Corso 60. PERUGIALiberati, Nunzi 61. PESAROVisani, Leopardi 62. PESCARAFioritoni, Spadano 63. PIACENZACavanna, Lazzaro 64. PINEROLOGriso 65. PISA Petrini/Benedetti 66. POTENZA Ricciuti, Vertone 67. RAVENNA Zaccaria, Molinari 68. REGGIO CAL. Nobile, Callea 69. REGGIO EMILIA Gugliotta,Masini 70. RIMINI Pasquini, Fattori 71. ROMA Annino, Bongarzoni 72. ROMA Andriani 73. ROMA 1 Foà, Petrucci 74. ROMA Cattolica Leone, De Stefano 75. ROMA R.Elena Petti, Pisani 76. ROMA S. Camillo Majolino, De Rosa 77. ROMA T. Vergata Amadori, Caravita 78. ROZZANO Santoro, Nozza 79. S. G. ROTONDO Musto, Merla 80. SASSARI Longinotti, Dore 81. SIENA Lauria, Gozzetti 82. TARANTO Mazza, Casulli 83. TORINO 1 Boccadoro 84. TORINO 2 Gallo, Pregno 85. TORINO MAURIZ. Poccardi, Gottardi 86. TORINO S. VITO Marinone, Ficara 87. TORINO VALD.SE Bazzan, Rus 88. TREVISO Foscolo, Gherlinzoni 89. TRIESTE De Sabbata 90. UDINE Fanin, Patriarca 91. VARESE Pinotti 92. VENEZIA Chisesi 93. VERBANIA Montanara, Luraschi 94. VERONA Pizzolo, Meneghini 95. VICENZA Rodeghiero, Elice We Are Grateful to All Patients, Nurses and Physicians of the Participating Centers


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