Mario Boccadoro

Gammie T, Lu CY, Ud-Din, PLoS One, 2015
Mieloma Multiplo: Malattia Rara
Roma 1-12-2015
Mario Boccadoro
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
Mieloma multiplo: malattia rara
• eccezionali progressi
• rete
Malattia rara, rarissima?
Incidenza nelle varie aziende
Immissione in Commercio
Molte orphan drugs poche AIC
Combinazioni
Managed entry agreement
Mieloma multiplo: malattia rara
• eccezionali progressi
• rete
Malattia rara, rarissima?
Incidenza nelle varie aziende
Immissione in Commercio
Molte orphan drugs poche AIC
Combinazioni
Managed entry agreement
Multiple Myeloma - incurable disease
Survival %
100
Complete Response: 13%
50
Median survival = 24 - 30 months
Median survival 6 years
Kumar S, Leukemia. 2014 May;28(5):1122-8.
Continuous improvement in overall
survival
Bergsagel MD 2104 ASCO Educational8Book
Mieloma multiplo: malattia rara
• eccezionali progressi
• rete
Malattia rara, rarissima?
Incidenza nelle varie aziende
Immissione in Commercio
Molte orphan drugs poche AIC
Combinazioni
Managed entry agreement
Mieloma Multiplo Working Party
Chairman
Mario Boccadoro
Co-chairman
Michele Cavo
Antonio Palumbo
BOARD
Baldini Luca
Corso Alessandro
Di Raimondo Francesco
Morabito Fortunato
Musto Pellegrino
Offidani Massimo
Patriarca Francesca
Petrucci Maria Teresa
Tosi Patrizia
We Are Grateful to All Patients, Nurses and
Physicians of the Participating Centers
1. ALESSANDRIA
2. ANCONA
3. AOSTA
4. ASCOLI PICENO
5. ASTI
6. AVELLINO
7. AVIANO
8. BARI
9. BARI
10. BELLUNO
11. BENEVENTO
12. BERGAMO
13. BOLOGNA
14. BOLZANO
15. BRA
16. BRESCIA
17. BRESCIA
18. BRINDISI
19. CAGLIARI
20. CAGLIARI
21. CAMPOBASSO
22. CANDIOLO
23. CATANIA
24. CATANZARO
25. CATTOLICA
26. CESENA
27. CIRIE'
28. COSENZA
29. CREMONA
30. CUNEO
31. FIRENZE
32. FOGGIA
33. FORLI’
34. FROSINONE
35. GALLARATE
36. GENOVA
37. FORLI’
38. GENOVA
Levis, Baraldi
Leoni, Offidani
Di Vito
Galieni
Favro, Ciravegna
Cantore, Volpe
Tirelli, Rupolo
Vacca, Ria
Liso
Pianezze
Di Lonardo, Vallone
Rambaldi, Galli
Baccarani,Cavo
Cortellazzo, Pescosta
Vanni, Stefani
Rossi, Crippa
Russo, Malagola
Quarta
Angelucci, Derudas
La Nasa, Ledda
Storti
Aglietta, Capaldi
Di Raimondo
Peta, Piro
Pasquini
Guardigni
Girotto, Freilone
Morabito
Lanza
Gallamini, Grasso
Bosi/Nozzoli
Capalbo
Amadori, Gentilini
Sala
Mozzana, Ciambelli
Gobbi, Canepa
Amadori, Gentilini
Gobbi, Canepa
39. GENOVA
40. GENOVA
41. IVREA
42. LATINA
43. LATINA
44. LECCE
45. MATERA
46. MESSINA
47. MESSINA
48. MILANO
49. MILANO
50. MILANO
51. MILANO
52. MILANO
53. MODENA
54. MODENA
55. MONZA
56. NAPOLI
57. NAPOLI
58. NAPOLI
59. NOCERA INF.
60. NOVARA
61. NUORO
62. ORBASSANO
63. PADOVA
64. PALERMO
65. PARMA
66. PAVIA
67. PERUGIA
68. PESARO
69. PESCARA
70. PIACENZA
71. PINEROLO
72. PISA
73. POTENZA
74. RAVENNA
75. REGGIO CALABRIA
76. REGGIO EMILIA
Carella, Spriano
Bacigalupo, Dominietto
Girotto, Aitoro
De Blasio
Cimino
Di Renzo
Fragasso
Brugiatelli
Musolino
Corradini, Montefusco
Morra
Ciceri
Lambertenghi, Baldini
Gianni
Marasca
Sacchi
Pogliani, Rossini
Pane,Catalano
Ferrara
Mettivier
D’Arco, Califano
Gaidano, Rossi
Gabbas
Saglio, Guglielmelli
Semenzato, Zambello
Mirto, Cangialosi
Rizzoli, Giuliani
Lazzarino, Corso
Martelli, Ballanti
Visani, Leopardi
Fioritoni, Spadano
Cavanna, Lazzaro
Griso
Petrini/Benedetti
Ricciuti, Vertone
Zaccaria, Cellini
Nobile, Callea
Gugliotta, Masini
77. RIMINI
78. RIONERO VULTURE
79. RIETI
80. ROMA
81. ROMA
82. ROMA
83. ROMA
84. ROMA
85. ROMA
86. ROMA
87. ROMA
88. ROMA
89. ROMA
90. ROZZANO
91. S. G. ROTONDO
92. SASSARI
93. SIENA
94. TARANTO
95. TERNI
96. TORINO
97. TORINO
98. TORINO
99. TREVISO
100. TRICASE
101. TRIESTE
102. UDINE
103. VENEZIA
104. VERBANIA
105. VERCELLI
106. VERONA
107. VICENZA
108. VITERBO
109. ISRAEL
110. JERUSALEM
111. KEFAR SABAH
112. ZERIFIM
113. HAIFA
Pasquini, Fattori
Musto
Capparella
Foà, Petrucci
De Fabritiis, Caravita
Andriani
Annino, Bongarzoni
Leone, De Stefano
Petti, Pisani
Majolino, De Rosa
Amadori
Avvisati
Recine
Santoro, Nozza
Cascavilla, Falcone
Dore, Podda
Lauria, Gozzetti
Mazza, Casulli
Liberati
Boccadoro
Pregno, Benevolo
Tarella, Gottardi
Gherlinzoni
Pavone
De Sabbata
Fanin, Patriarca
Chisesi
Montanara, Luraschi
Santagostino
Pizzolo, Meneghini
Rodeghiero, Elice
Montanaro
Nagler
Ben Yehuda
Manor
Kornberg
Attias
Mieloma multiplo: malattia rara
• eccezionali progressi
• rete
Malattia rara, rarissima?
Incidenza nelle varie aziende
Immissione in Commercio
Molte orphan drugs poche AIC
Combinazioni
Managed entry agreement
Orpha Number
Disease
Incidence
Prevalence
29073
Multiple Myeloma
11,9P 6.0 I
fewer than 1 in 2,000 people. Diseases that are statistically rare, but
life-threatening, chronically debilitating, or inadequately treated
Mieloma Multiplo: malattie diverse
Non alterazioni
molecolari
Presenza di
t(4;14) o del(17p)
t(4;14) or del(17p) about 15% of myeloma patients
Kumar S, Leukemia. 2014 May;28(5):1122-8
Mieloma Multiplo
Ricoveri sul totale regionale presso
Città della Salute
30%
Provenienza pazienti ricoverati presso Città della Salute
14%
Altre Nazioni ??
Calcolo prevalenza malattie rare nei vari centri??
Mieloma multiplo: malattia rara
• eccezionali progressi
• rete
Malattia rara, rarissima?
Incidenza nelle varie aziende
Immissione in Commercio
Molte orphan drugs poche AIC
Combinazioni
Managed entry agreement
Drug with Orphan designation 2015
(3E,5E)-3,5-bis[(4-fluoro-3-nitrophenyl)methylidene]-1-(prop-2-enoyl)azepan-4-0ne
17-allylamino-17-demethoxygeldanamycin
6-[4-Deoxy-4-[(2E,4E)-tetradecadienoylglycyl]amino-L-glycero-B-L-manno-heptopyranosyl]amino-9H-purine
Acadesine
Aplidine
Bortezomib
Carfilzomib
Daratumumab
Dexamethasone (40 mg tablet)
Doxorubicin hydrochloride (liposomal)
Elotuzumab
Filanesib
Genetically modified serotype 5/3 adenovirus coding for granulocyte-macrophage colony-stimulating factor
Human anti-intercellular adhesion molecule-1 monoclonal antibody
Humanized immunoglobulin monoclonal antibody against CD38
Imexon
Ixazomib citrate
Lenalidomide
Marizomib
Maytansinoid-conjugated humanized monoclonal antibody against CD56
Melphalan
Milatuzumab
N-(methyl-diazacyclohexyl-methylbenzamide)-azaphenyl-aminothiopyrrole
N2'-Deacetyl-N2'-[4-methyl-4-(oxobuthyldithio)-1-oxopentyl]-maytansine-chimerized anti- CD138 IgG4 monoclonal antibody
Oprozomib
Panobinostat
Perifosine
Plitidepsin
Pomalidomide
combinant histidine-tagged idiotype immunoglobulin Fab fragment of clonal B-cell receptors
Recombinant human monoclonal IgM antibody targeting glucose-regulated protein 78
Siltuximab
Synthetic signal peptide of human Mucin-1 (amino acids 1-21)
Thalidomide
Vorinostat
Marketing Authorization with orphan designation
USA
ALKERAN
FARYDAK
IMNOVID
KYPROLIS
MOZOBIL
POMALYST
REVLIMID
THALIDOMIDE CELGENE
THALOMID
VELCADE
EU
FARYDAK
IMNOVID
MOZOBIL
REVLIMID
THALIDOMIDE CELGENE
Mieloma multiplo: malattia rara
• eccezionali progressi
• rete
Malattia rara, rarissima?
Incidenza nelle varie aziende
Immissione in Commercio
Molte orphan drugs poche AIC
Combinazioni
Managed entry agreement
21
Phase 2 Trial of Carfilzomib-LenalidomideDexamethasone (CRd) in TE NDMM patients
• Phase 2, open-label, single-centre study
Induction
N = 31
patients
with
NDMM
Consolidation
Maintenance*
CRd:
CRd:
CRd:
CFZ: 36 mg/m2,a,
30 min, D1–2, 8–9,
15–16
LEN: 25 mg, D1–21
DEX: 40 mg, weekly
CFZ: LTD, D1–2,
8–9,15–16
LEN:15-25, D1–21
DEX: 20 mg or LTD
weekly
CFZ: LTD, D1–2,
15–16
LEN: LTD, D1–21
DEX: LTD, weekly
Four 28-day cycles
Ten 28-day cycles
Four 28-day cycles
ASCT
* Off-protocol: LEN monotherapy maintenance at LTD from cycle 19
• Primary endpoint: sCR after consolidation;
secondary endpoints: ORR, survival, DoR, TTP, safety and tolerability
• Median age was 62 years, 50% of patients had high-risk cytogenetics
a
20 mg/m2 for Cycle 1, D1-2
CRd, carfilzomib, Lenalidomide, low-dose dexamethasone; LTD, last tolerated dose;
TE, transplant-eligible
Zimmerman TM, et al. EHA 2014: abstract P347. Poster presentation.
NCT01816971.
22
Phase 2 Trial of CRd in NDMM
Summary of Outcomes
Efficacy
• ORR (≥ PR) after 4 cycles of
CRd was 96%
• sCR + CR = 79%
64%
92%
100%
Zimmerman TM, et al. EHA 2014: abstract P347. Poster presentation.
Mieloma multiplo: malattia rara
Nuove medicine con differente meccanismo d’azione
Combinazioni
inibitori del proteasoma
immunomudulating drugs
anticorpi monoclonali
Aumento efficacia -> Guarigione?
Aumento costi
Mieloma multiplo: malattia rara
• eccezionali progressi
• rete
Malattia rara, rarissima?
Incidenza nelle varie aziende
Immissione in Commercio
Molte orphan drugs poche AIC
Combinazioni
Managed entry agreement
Conclusioni
Sempre più malattie rare
Sempre piu farmaci mirati
Precision/personalized medicine
Doctors have always recognized that every
patient is unique
President Obama, January 2015