ITALIAN MYELOMA NETWORK
INTERIM ANALYSIS
PROSPECTIVE RANDOMIZED TRIAL
NEWLY DIAGNOSED PATIENTS, AGE > 65 YEARS
MELPHALAN, PREDNISONE, THALIDOMIDE (MPT)
versus
MELPHALAN PREDNISONE (MP)
Antonio Palumbo
Dept. Hematology, University of Torino
TREATMENT SCHEDULE
MELPHALAN 4 mg/m2 7 days/month for 6 courses
+
PREDNISONE 40 mg/m2 7 days/month for 6 courses
+
THALIDOMIDE 100 mg/d continuously until relapse
INTERIM ANALYSIS
Intention to treat analysis
177 Patients enrolled within May 2004
Minimum follow-up 6 months
Dept. Hematology, University of Torino
PATIENT CHARACTERISTICS
MPT
MP
No. of patients
89
88
Median age (range)
71 (61-82)
73 (60-85)
Stage at diagnosis
IIA (%)
44
43
IIIA (%)
47
49
B
(%)
9
8
Median ß2-Microgl. mg/L
3.4
3.6
(range)
(0.2-37.5)
(0.3-15)
M-protein
IgG (%)
58
64
IgA (%)
32
21
BJ (%)
10
15
Dept. Hematology, University of Torino
ADVERSE EVENTS
MPT
MP
WHO (grade)
1-2
3-4
1-2
3-4
Hematologic (%)
29
18
35
25
Constipation (%)
28
7
-
-
Neurologic (%)
32
9
11
-
Cardiac (%)
17
3
3
4
Cutaneous (%)
15
2
3
-
Infection (%)
14
10
12
1
Thromboemb. (%)
19
4
Early death (%)
5
5
Dept. Hematology, University of Torino
THROMBOEMBOLISM
(MPT)
No prophylaxis
(61 patients)
· 1.6% Arterial occlusion
· 4.9% Pulmonary thromboembolism
· 21.3% Deep-vein thrombosis
Enoxaparin 0.4 ml/d for 4 months (28 patients)
· 0% Arterial occlusion
· 0% Pulmonary thromboembolism
· 7.1% Deep-vein thrombosis
Dept. Hematology, University of Torino
THALIDOMIDE DISCONTINUATION
(MPT)
50
Discontinuation 12% TVP
e 40
10% Neurologic
cn
6% Constipation
ed
Reduction
di 30
6% Cardiac
cnI
8% Miscellaneous
f 20
o
% 10
15% Neurologic
6% Constipation
0
6% Miscellaneous
0
2
4
6
8
10
12
14
16
18
20
22
24
Months
Dept. Hematology, University of Torino
RESPONSE TO THERAPY
100
8.4%
80
14.5%
28%
esno 60
PD
p
25.3%
se
NR (0-50)
R
77.1%
f
40
PR (50-100)
o
%
20
46.7%
0
MPT
MP
Dept. Hematology, University of Torino
RESPONSE TO THERAPY
100
80
77.1%
es
PR (50-74)
15.6%
nop 60
s
46.7%
PR (75-99)
e
33.8%
Rf 40
o
28%
CR + nCR
%
20
27.7%
13.3%
0
5.4%
MPT
MP
Dept. Hematology, University of Torino
EVENT-FREE SURVIVAL
(median follow up 13.6 months)
1
0.8
n
0.6
rtioop
ro
0.4
MPT
roP
p<0.001
0.2
MP
0
0
5
10
15
20
25
30
35
Months
Dept. Hematology, University of Torino
OVERALL SURVIVAL
1
MPT
0.8
n
0.6
rtio
MP
op 0.4
roP
p=0.1
0.2
0
0
5
10
15
20
25
30
35
Months
Dept. Hematology, University of Torino
CONCLUSIONS I
MPT (%)
MP (%) P-value
DVT:
19
4
0.003
Neurotoxicity:
41
11
<0.001
Infections:
24
13
0.1
Early deaths:
5
5
1
Dept. Hematology, University of Torino
CONCLUSIONS II
MPT (%)
MP(%)
P-value
CR + nCR:
27.7
5.4
<0.001
Median EFS
25.2
13.7
<0.001
OS @ 33 months
78.7
68.2
0.1
Dept. Hematology, University of Torino
ACKNOWLEDGMENTS
1. ANCONA
P. Leoni, M.Offidani
30. PADOVA
G. Semenzato, R. Zambello
Zambello
2. ASCOLI PICENO
P. Galieni, C. Bigazzi
31. PALERMO
S. Mirto, C. Cangialosi
3. ALESSANDRIA
A. Levis, A. Baraldi
32. PARMA
Rizzoli, N. Giuliani
4. ASTI
E. Scassa, E. Campa
33. PERUGIA
A. M. Liberati, M. Nunzi
5. AVELLINO
N. Cantore, S. Volpe
34. PESARO
G. Visani, G. Leopardi
6. BARI
F. Dammacco, V. M. Lauta
35. PIACENZA
L. Cavanna, A. Lazzaro
7. BERGAMO
T. Barbui, M. Galli
36. POTENZA
F. Ricciuti, D. Vertone
8. BOLOGNA
M. Cavo, P.Tosi
37. RAVENNA
A. Zaccaria, A. Molinari
9. BRA
A. Vanni, S. Stefani
38. REGGIO CALABRIA
F. Nobile, V. Callea
10. CAGLIARI
E. Angelucci, A. Carubelli
39. REGGIO EMILIA
L.Gugliotta, L. Masini
11. CAGLIARI
G. Mantovani
40. RIMINI
E. pasquini, P. Fattori
12. CANDIOLO
M. Aglietta, A. Capaldi
41. ROMA 1
R. Foà, M.T. Petrucci
13. CATANIA
R. Giustolisi, F. Di Raimondo
42. ROMA La Cattolica
G. Leone, V. De Stefano
14. CATTOLICA
E. Pasquini
43. ROMA R.Elena
M. C. Petti, F. Pisani
15. CESENA
L. Guardigni
44. ROMA Tor Vergata
S. Amadori, T. Caravita
16. CHIOGGIA
R. Battista
45. ROMAS. Camillo
I. Majolino, L De Rosa
17. CREMONA
R. Passalacqua, S. Morandi
46. ROZZANO
A. Santoro, A. Nozza
18. CUNEO
A. Gallamini, M. Grasso
47. S. G. ROTONDO
P. Musto, E. Merla
19. FOGGIA
M.Monaco, C. Ferrandina
48. SASSARI
M. Longinotti, F. Dore
20. FORLI'
D. Amadori, P. Gentilini
49. SIENA
F. Lauria, A. Gozzetti
21. GENOVA
M. Gobbi, L. Canepa
50. TARANTO
P. Mazza, A. Casulli
22. MESSINA
M. Brugiatelli, D. Mamone
51. TREVISO
G. Foscolo, F. Gherlinzoni
23. MILANO
P. Corradini, V. Montefusco
52. TORINO 1
M. Boccadoro, A. Bertola
24. MONTEFIASCONE
M. Montanaro,
anaro, P. Niscola
53. TORINO 2
E. Gallo, P. Pregno
25. MONZA
E. Pogliani, F. Rossini
54. TORINO SAN VITO
C. Marinone, F. Ficara
26. NAPOLI
B. Rotoli, L. Catalano
55. TORINO VALDESE
M. Bazzan, C. Rus
27. NOCERA INF.
A D'Arco, C. Califano
56. TORINO MAURIZ.
G. Poccardi, E. Gottardi
28. NUORO
G. Latte, A. Palmas
57. VERONA
G. Pizzolo, V. Meneghini
29. ORBASSANO
G. Saglio, T. Guglielmelli
58. VICENZA
F. Rodeghiero, F. Elice