L esperienza dell European Myeloma Network Trialist Group



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Roma February 14, 2005 GIMEMA Stresa May 17, 2008 EMNTG IF AT FIRST AN IDEA IS NOT ABSURD, THEN THERE IS NO HOPE FOR IT L esperienza dell European Myeloma Network Trialist Group

SURVIVAL OF COOPERATIVE GROUPS Research is moving to China, India where costs are lower Companies prefer big groups for studies of global impact Small groips are dying YESTERDAY TODAY

AUSTRALIA NORWAY SWEDEN FINLAND DENMARK UNITED KINGDOM ISRAEL NETHERLANDS GERMANY CZECH REPUBLIC AUSTRIA POLAND SPAIN ITALY GREECE TURKEY

A RANDOMIZED PHASE III STUDY TO COMPARE BORTEZOMIB, MELPHALAN, PREDNISONE (VMP) WITH HIGH DOSE MELPHALAN FOLLOWED BY BORTEZOMIB, LENALIDOMIDE, DEXAMETHASONE (VRD) CONSOLIDATION AND LENALIDOMIDE MAINTENANCE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA ITALY INDUCTION 1500 pts 3 VCD + CY GERMANY 4 VMP (500 pts) 1 HDM (500 pts) 2 HDM (500 pts) NONE VRD NONE VRD NONE VRD Maintenance Maintenance Maintenance NETHERLAND AND NORDIC

A PHASE 3, MULTICENTRE, RANDOMIZED, CONTROLLED STUDY TO DETERMINE THE EFFICACY AND SAFETY OF CYCLOPHOSPHAMIDE, LENALIDOMIDE AND DEXAMETHASONE (CRD) versus MELPHALAN (200 mg/m2) FOLLOWED BY STEM CELL TRANSPLANT IN NEWLY DIAGNOSED MULTIPLE MYELOMA SUBJECTS INDUCTION EAST EUROPE 660 pts RD (4 cycles) ARM A (190 pts) CRD X 6 courses ARM B (190 pts) MEL200 (1-2 cycles) Maintenance Maintenance ARM A1 ARM A2 ARM B1 ARM B2 RP R RP R AUSTRALIA

A PHASE 3, INTERGROUP MULTICENTRE, RANDOMIZED, CONTROLLED 3 ARM PARALLEL GROUP STUDY TO DETERMINE THE EFFICACY AND SAFETY OF LENALIDOMIDE IN COMBINATION WITH DEXAMETHASONE (Rd) VERSUS MELPHALAN, PREDNISONE AND LENALIDOMIDE (MPR) versus CYCLOPHOSPHAMIDE, PREDNISONE AND LENALIDOMIDE (CPR) IN NEWLY DIAGNOSED MULTIPLE MYELOMA SUBJECTS INDUCTION 660 pts ITALY ARM A (220 pts) Rd X 9 courses ARM B (220 pts) MPR X 9 courses ARM C (220 pts) CPR X 9 courses Maintenance Maintenance Maintenance ARM A1 ARM A2 ARM B1 ARM B2 ARM C1 ARM C3 R RP R RP R RP GERMANY

Legislazione no profit: traferimento esiti ricerca scientifica Bortezomib (twice-weekly) Bortezomib (once weekly) 2-year PFS 56% 58% Sensory PN Grade 3/4 14% 2% Discontinuation 16% 4% Canada Bortezomib infusione settimanale Italia Permane infusione bisettimanale Palumbo et al. ASH 2009 (abstract 128); oral presentation

CENTRAL ORGANIZATION PRECLINICAL/LAB OFFICE GRANT OFFICE FINANCIAL OFFICE CLINICAL TRIAL OFFICE

LOCAL ORGANIZATION LAB AND BIOBANKING

Support to research Phase I unit Financial office Legal office Patent office Grant office Data managing office Statistical office Fondazione

DISTRICT ORGANIZATION PHASE I/II STUDIES CARFILZOMIB POMALIDOMIDE BORTEZOMIB SC. CNTO

Meta analysis and retrospective studies MP versus MPT for previously untreated elderly patients with multiple myeloma: A meta analysis of survival of 1682 individual patient data from 6 randomized clinical trials. A. Waage, A. P. Palumbo, P. Fayers, M. Beksac, C. Hulin, J. Y. Mary, S. Bringhen, P. Sonneveld, P. Wijermans, T. Facon, NMSG, GIMEMA, TMSG, HOVON, IFM, European Myeloma Network; St. Olavs Hospital/NTNU, Trondheim, Norway; Divisione di Ematologia dell'università di Torino, A.O.U. S. Giovanni Battista, Torino, Italy; University of Aberdeen, Aberdeen, Scotland; Ankara University, Ankara, Turkey; Department of Hematology, University Hospital, Nancy, France; INSERM U717, Paris, France; Erasmus MC, Rotterdam, Netherlands; Hospital Leyenburg, Hague, Netherlands; Hopital Huriez, Service des Maladies du Sang, Lille, France GIMEMA IFM I IFM II NMSG HOVON TMSG Age, Years > 65 65-74 75 > 65 > 65 > 55 No of pts 331 321 229 354 333 114

Guidelines The use of bisphosphonates in multiple myeloma Terpos E, Sezer O, Croucher PI, García-Sanz R, Boccadoro M, San Miguel J, Ashcroft J, Bladé J, Cavo M, Delforge M, Dimopoulos MA, Facon T, Macro M, Waage A, Sonneveld P; European Myeloma Network. Ann Oncol. 2009 Aug;20(8):1303-17. Epub 2009 May 22. Review.PMID: 19465418

PubMed.gov publications 2010: 19 publications 2009: 20 publications 2008: 18 publications EMNTG 2007: 11 publications 2006: 8 publications 2005: 7 publications

Publications: 2010 J Clin Oncol. 2010 May 1;28(13):2259-66. J Clin Oncol. 2010 Apr 20;28(12):2077-84. J Clin Oncol. 2010 Mar 20;28(9):1599-605. J Clin Oncol. 2010 Feb 10;28(5):800-7. Blood. 2010 Mar 25;115(12):2332-3. Blood. 2010 Mar 11;115(10):1873-9. Lancet Oncol. 2010 Jan;11(1):3-4. Leukemia. 2010 Apr 22. Leukemia. 2010 Apr 8.

Conclusion Important global cooperative group Relevant phase III studies 80% of the new molecules are within the group More trials than PIs

Take home message Specialization Eccellenti in 1 cosa o mediocri in 100 Team effort Governance Freedom Support Delega e sinergia fra eccellenze Studi di fase 3 blindati Studi di fase 1-2 liberi Clinico, legale, segretariale, etc

We Are Grateful to All Patients, Nurses, Physicians Insitutions of the Participating Centers 1. ALESSANDRIA Levis, Baraldi 2. ANCONA Leoni, Offidani 3. AOSTA Di Vito 4. ASCOLI PICENO Galieni, 5. ASTI Favro 6. AVELLINO Cantore, Volpe 7. AVIANO Tirelli, Rupolo 8. BARI Dammacco, Ria 9. BARI Liso 10. BELLUNO Pianezze 11. BENEVENTO Di Lonardo, Vallone 12. BERGAMO Rambaldi, Galli 13. BOLOGNA Baccarani,Cavo 14. BOLZANO Cortellazzo, Pescosta 15. BRA Vanni, Stefani 16. BRESCIA Rossi, Crippa 17. BRESCIA Russo, Malagola 18. BRINDISI Quarta 19. CAGLIARI Angelucci, Derudas 20. CAGLIARI La Nasa, Ledda 21. CAMPOBASSO Storti 22. CANDIOLO Aglietta, Capaldi 23. CATANIA Giustolisi,Di Raimondo 24. CATANZARO Peta, Piro 25. CATTOLICA Pasquini 26. CESENA Guardigni 27. CIRIE' Girotto, Freilone 28. COSENZA Morabito 29. CREMONA Morandi 30. CUNEO Gallamini, Grasso 31. FIRENZE Bosi/Nozzoli 32. FOGGIA Capalbo 33. FORLI Amadori, Gentilini 34. FROSINONE Sala 35. GALLARATE Ciambelli 36. GENOVA Gobbi, Canepa 37. FORLI Amadori, Gentilini 38. FROSINONE Sala 39. GALLARATE Ciambelli 40. GENOVA Gobbi, Canepa 41. GENOVA Carella, Spriano 42. GENOVA Bacigalupo, Dominietto 43. IVREA Girotto, Aitoro 44. LATINA De Blasio 45. LATINA Cimino 46. LECCE Di Renzo 47. MATERA Fragasso 48. MESSINA Brugiatelli 49. MESSINA Musolino 50. MILANO Corradini, Montefusco 51. MILANO Morra 52. MILANO Ciceri 53. MILANO Lanbertenghi, Baldini 54. MILANO Gianni 55. MODENA Torelli 56. MODENA Sacchi 57. MONZA Pogliani, Rossini 58. NAPOLI Rotoli,Catalano 59. NAPOLI Ferrara 60. NAPOLI Mettivier 61. NOCERA INF. D Arco, Califano 62. NOVARA Gaidano, Rossi 63. NUORO Gabbas 64. ORBASSANO Saglio, Guglielmelli 65. PADOVA Semenzato, Zambello 66. PALERMO Mirto, Cangialosi 67. PARMA Rizzoli, Giuliani 68. PAVIA Lazzarino, Corso 69. PERUGIA Liberati, Nunzi 70. PESARO Visani, Leopardi 71. PESCARA Fioritoni, Spadano 72. PIACENZA Cavanna, 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. TORINO Boccadoro 98. TORINO Gallo, Pregno 99. TORINO Poccardi, Aragno 100. TREVISO Foscolo, Gherlinzoni 101. TRICASE Pavone 102. TRIESTE De Sabbata 103. UDINE Fanin, Patriarca 104. VENEZIA Chisesi 105. VERBANIA Montanara, Luraschi 106. VERCELLI Santagostino 107. VERONA Pizzolo, Meneghini 108. VICENZA Rodeghiero, Elice 109. VITERBO Montanaro