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 dell’Università 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.
15
Embed
Bortezomib, Melphalan, Prednisone and Thalidomide (VMPT) Followed by Maintenance with Bortezomib and Thalidomide (VT) for Initial Treatment of Elderly.
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Bortezomib, Melphalan, Prednisone and Thalidomide (VMPT)
Followed
by Maintenance with Bortezomib and Thalidomide (VT) for
Initial Treatment of Elderly Multiple Myeloma Patients
Italian Multiple Myeloma Group1.Divisione di Ematologia dell’Università 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.
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
• 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
VMPCycles 1-9Bortezomib 1.3 mg/m2 IV: days 1,8,15,22*Melphalan 9 mg/m2 and prednisone 60 mg/m2 days 1-4
VMPTCycles 1-9Bortezomib 1.3 mg/m2 IV: days 1,8,15,22*Melphalan 9 mg/m2 and prednisone 60 mg/m2 days 1-4Thalidomide 50 mg/day continuously
RANDOMIZE
9 x 5-week cycles in both arms
MAINTENANCEBortezomib 1.3 mg/m2 IV: days 1,15Thalidomide 50 mg/day continuously
NO MAINTENANCE
Until relapse
* 66 VMP patients and 73 VMPT-VT patients were treated with twice weekly infusions of Bortezomib
Patient Characteristics
27%27% > 75 years
3.842 microglobulin-mg/L (median)
Chromosome abnormalities
17%14% t(4;14)
5%3% t(14;16)
68%71% 65–74 years5%2% < 65 years
7171Age (median)
17%13% Del 17
VMPT VT
(N=254)
VMP
(N=257)
% o
f p
atie
nts
% o
f p
atie
nts
CRCR VGPRVGPR PRPRCRCR VGPRVGPR PRPR
% o
f p
atie
nts
% o
f p
atie
nts
SDSD PDPD SDSD PDPD
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
2 42 6
3 1
1 7
1
0
5
1 0
1 5
2 0
2 5
3 0
3 5
4 0 3 8
2 1
3 0
6
1
0
5
1 0
1 5
2 0
2 5
3 0
3 5
4 0
Best Response Rate
% o
f p
atie
nts
Months
VMP VMPTVT
CR: VMPTVT
PR: VMPTVT
CR: VMP
PR: VMP
100
80
60
40
20
0
Time to first response and time to CR
0 5 10 15 20 25 300 5 10 15 20 25 30
Time to next therapy Progression free survival
% o
f p
atie
nts
Time to next therapy Progression 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%
VMPTVT
VMP
Months
VMPT VT
VMP
P = 0.0060.00
0.25
0.50
0.75
1.00
0 10 20 30 40 50 60
0.00
0.25
0.50
0.75
1.00
0 10 20 30 40 50 60
Overall survival
Months
VMP: OS @ 3 years = 84%
VMPTVT: OS @ 3 years = 86%
% o
f p
atie
nts
VMP
VMPTVT
P = 0.60
0.00
0.25
0.50
0.75
1.00
0 10 20 30 40 50 60
Grade 3-4 Hematologic Adverse Events
Patients (%)
VMPTVTVMP
0 5 10 15 20 25 30 35 40
Anaemia
Thrombocytopenia
Neutropenia P=0.02
Grade 3-4 Non-hematologic Adverse Events
Patients (%)
VMPTVTVMP
0 5 10 15 20 25
Drop Out for PN
Drop Out for AE
DVT/PE
Cardiologic
Infections
Sensory neuropathy
P=0.04
P=0.05
Efficacy and Toxicity by Bortezomib schedule
46.8 mg/m267.6 mg/m267.6Total planned dose
4%16%NAPN discontinuation
57%57%48%PFS @ 2 years
2%14%13% Grade 3-4
NA
44%
30%
VMP* (VISTA)
40 mg/m2
21%
23%
VMP once weekly N=190°
Sensory PN
43% Any grade
41 mg/m2Total 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
PFS according to Bortezomib schedule
Twice weekly: PFS @ 3 years =45%
Once weekly: PFS @ 3 years = 50%
% o
f p
atie
nts
Months
Once weekly
Twice weekly
P = 0.870.00
0.25
0.50
0.75
1.00
0 10 20 30 40 50 60
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
Conclusions 2• Best available treatment option for elderly patient