Bortezomib, Melphalan, Prednisone and Thalidomide (VMPT) Followed by Maintenance with Bortezomib and Thalidomide (VT) for Initial Treatment of Elderly.

Presentazione sul tema: "Bortezomib, Melphalan, Prednisone and Thalidomide (VMPT) Followed by Maintenance with Bortezomib and Thalidomide (VT) for Initial Treatment of Elderly."— Transcript della presentazione:

1 Bortezomib, Melphalan, Prednisone and Thalidomide (VMPT) Followed by Maintenance with Bortezomib and Thalidomide (VT) for Initial Treatment of Elderly Multiple Myeloma Patients GIMEMA: Italian Multiple Myeloma Network Boccadoro M(1), Bringhen S(1), Gaidano G(2), Ria R(3), Offidani M(4), Patriarca F(5), Nozzoli C(6), Musto P(7), Petrucci MT(8), Palumbo A(1). Italian Multiple Myeloma Group 1.Divisione di Ematologia dellUniversità di Torino, A.O.U. San Giovanni Battista, Torino, Italy; 2.Divisione di Ematologia, Università del Piemonte Orientale Amedeo Avogadro e Ospedale Maggiore della Carità, Novara, Italy; 3.Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione di Medicina Interna e Oncologia Clinica, Università di Bari, Bari, Italy; 4.Clinica di Ematologia, A.O.U. Ospedali Riuniti, Ancona, Italy; 5.Divisione di Ematologia, Istituto Nazionale Tumori, Milano, Italy; 6.Clinica Ematologica, Università di Udine, Udine, Italy; 7.Dipartimento di Ematologia, Università di Firenze, A.O.U. Careggi, Firenze, Italy; 8.Dipartimento di Oncoematologia, IRCCS CROB Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy; 9.Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Ospedale Umberto I, Roma, Italy.

2 Aims Best experimental therapy: 4 drug combo VMPT Maintenance VT Best standard of care 3 drug combo VMP Safety and efficacy of weekly infusion of bortezomib

3 511 patients (older than 65 years) randomized from 58 Italian centers Patients: Symptomatic multiple myeloma/end organ damage with 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 * 66 VMP patients and 73 VMPT-VT patients were treated with twice weekly infusions of Bortezomib

4 Patient Characteristics 27% > 75 years 3.84 2 microglobulin-mg/L (median) Chromosome abnormalities 17%14% t(4;14) 5%3% t(14;16) 68%71% 65–74 years 5%2% < 65 years 71 Age (median) 17%13% Del 17 VMPT VT (N=254) VMP (N=257)

5 % of patients CRVGPRPR CRVGPRPR SDPD SDPD 89% 59% 38% VMPT VT (N=250) 0.01 0.03 0.0008 P value 81%> PR 50%> VGPR 24%CR VMP (N=253) VMPT VTVMP Best Response Rate

6 % of patients Months VMPVMPT VT CR: VMPT VT PR: VMPT VT CR: VMP PR: VMP 100 80 60 40 20 0 Time to first response and time to CR 0 5 10 1520 25 30

7 Time to next therapy Progression free survival % of patients Time to next therapyProgression free survival Median follow-up 26.5 months VMP: PFS @ 3 years = 40% VMPT VT: PFS @ 3 years = 54% P = 0.006 VMP: TTNT @ 3 years = 55% VMPT VT: TTNT @ 3 years = 69% VMPT VT VMP Months 0.00 0.25 0.50 0.75 1.00 0102030405060

8 Overall survival Months VMP: OS @ 3 years = 84% VMPT VT: OS @ 3 years = 86% % of patients VMP VMPT VT P = 0.60 0.00 0.25 0.50 0.75 1.00 0102030405060

9 Grade 3-4 Hematologic Adverse Events Patients (%) VMPT VTVMP 0510152025303540 Anaemia Thrombocytopenia Neutropenia P=0.02

10 Grade 3-4 Non-hematologic Adverse Events Patients (%) VMPT VT VMP 0510152025 Drop Out for PN Drop Out for AE DVT/PE Cardiologic Infections Sensory neuropathy P=0.04 P=0.05

11 Efficacy and Toxicity by Bortezomib schedule 46.8 mg/m 2 67.6 mg/m 2 67.6 Total planned dose 4%16%NA PN discontinuation 57% 48%PFS @ 2 years 2%14%13% Grade 3-4 NA 44% 30% VMP* (VISTA) 40 mg/m 2 21% 23% VMP once weekly N=190° Sensory PN 43% Any grade 41 mg/m 2 Total delivered dose 25%CR VMP twice weekly N=63° *San Miguel JF et al. New Eng J Med 2008; 359: 906-17; ° 3 patients in twice weekly and 1 patient in once weekly group are not evaluable because they never start therapy; PN: peripheral neuropathy

12 PFS according to Bortezomib schedule Twice weekly: PFS @ 3 years =45% Once weekly: PFS @ 3 years = 50% % of patients Months Once weekly Twice weekly P = 0.87

13 0.00669%55% TTNT @ 3 years 86% 54% 38% VMPT VT (N=250) 0.60 0.006 0.0008 P value 40% PFS @ 3 years 84%OS @ 3 years 24%CR VMP (N=253) Conclusions 1

14 Conclusions 2 Best available treatment option for elderly patient VMPT VT improves PFS in comparison with VMP VMPT VT improves response rate and PFS VMPT increases CR rate VT maintenance improves PFS Once-weekly bortezomib reduces peripheral neuropathy

15 We Are Grateful to All Patients, Nurses and Physicians of the Participating Centers 1. ALESSANDRIALevis, Baraldi 2. ANCONALeoni, Offidani 3. AOSTADi Vito 4. ASCOLI PICENOGalieni, 5. ASTIFavro 6. AVELLINOCantore, Volpe 7. AVIANOTirelli, Rupolo 8. BARIDammacco, Ria 9. BARILiso 10. BELLUNOPianezze 11. BENEVENTODi Lonardo, Vallone 12. BERGAMORambaldi, Galli 13. BOLOGNABaccarani,Cavo 14. BOLZANOCortellazzo, Pescosta 15. BRAVanni, Stefani 16. BRESCIARossi, Crippa 17. BRESCIARusso, Malagola 18. BRINDISIQuarta 19. CAGLIARIAngelucci, Derudas 20. CAGLIARILa Nasa, Ledda 21. CAMPOBASSOStorti 22. CANDIOLOAglietta, Capaldi 23. CATANIAGiustolisi,Di Raimondo 24. CATANZAROPeta, Piro 25. CATTOLICAPasquini 26. CESENAGuardigni 27. CIRIE'Girotto, Freilone 28. COSENZAMorabito 29. CREMONAMorandi 30. CUNEOGallamini, Grasso 31. FIRENZEBosi/Nozzoli 32. FOGGIACapalbo 33. FORLIAmadori, Gentilini 34. FROSINONESala 35. GALLARATECiambelli 36. GENOVAGobbi, Canepa 37. FORLIAmadori, Gentilini 38. FROSINONESala 39. GALLARATECiambelli 40. GENOVAGobbi, Canepa 41. GENOVACarella, Spriano 42. GENOVABacigalupo, Dominietto 43. IVREAGirotto, Aitoro 44. LATINADe Blasio 45. LATINACimino 46. LECCEDi Renzo 47. MATERAFragasso 48. MESSINABrugiatelli 49. MESSINAMusolino 50. MILANOCorradini, Montefusco 51. MILANOMorra 52. MILANOCiceri 53. MILANOLambertenghi, Baldini 54. MILANOGianni 55. MODENATorelli 56. MODENASacchi 57. MONZAPogliani, Rossini 58. NAPOLIRotoli,Catalano 59. NAPOLIFerrara 60. NAPOLIMettivier 61. NOCERA INF.DArco, Califano 62. NOVARAGaidano, Rossi 63. NUOROGabbas 64. ORBASSANOSaglio, Guglielmelli 65. PADOVASemenzato, Zambello 66. PALERMO Mirto, Cangialosi 67. PARMARizzoli, Giuliani 68. PAVIALazzarino, Corso 69. PERUGIAMartelli, Ballanti 70. PESAROVisani, Leopardi 71. PESCARAFioritoni, Spadano 72. PIACENZACavanna, Lazzaro 73. PINEROLO Griso 74. PISA Petrini/Benedetti 75. POTENZA Ricciuti, Vertone 76. RAVENNA Zaccaria, Cellini 77. REGGIO CAL. Nobile, Callea 78. REGGIO EMILIA Gugliotta, Masini 79. RIMINI Pasquini, Fattori 80. RIONERO VULTURE Musto 81. RIETI Capparella 82. ROMA Foà, Petrucci 83. ROMA De Fabritiis, Caravita 84. ROMA Andriani 85. ROMA Annino, Bongarzoni 86. ROMA Leone, De Stefano 87. ROMA Petti, Pisani 88. ROMA Majolino, De Rosa 89. ROMA Amadori 90. ROMA Avvisati 91. ROMA Recine 92. ROZZANO Santoro, Nozza 93. S. G. ROTONDO Cascavilla, Falcone 94. SASSARI Dore, Podda 95. SIENA Lauria, Gozzetti 96. TARANTO Mazza, Casulli 97. TERNI Liberati 98. TORINO Boccadoro 99. TORINO Pregno, Benevolo 100. TORINO Tarella, Gottardi 101. TREVISO Gherlinzoni 102. TRICASE Pavone 103. TRIESTE De Sabbata 104. UDINE Fanin, Patriarca 105. VENEZIA Chisesi 106. VERBANIA Montanara, Luraschi 107. VERCELLI Santagostino 108. VERONA Pizzolo, Meneghini 109. VICENZA Rodeghiero, Elice 110. VITERBO Montanaro