Bortezomib Vs High-Dose Dexamethasone
in Relapsed Multiple Myeloma:
Results of a Large Randomized Phase 3 Study
Paul G. Richardson,1 Pieter Sonneveld,2 Michael W. Schuster,3 David Irwin,4
Edward A. Stadtmauer,5 Thierry Facon,6 Jean-Luc Harousseau,7 Dina Ben-Yehuda,8 Sagar Lonial,9
Hartmut Goldschmidt,10 Donna Reece,11 Jesus F. San Miguel,12
Joan Bladé,13 Mario Boccadoro,14 Jamie Cavenagh,15 William S. Dalton,16
Anthony L. Boral,17 David Schenkein,17 Kenneth C. Anderson1
1Dana-Farber Cancer Institute, 2University Hospital Rotterdam, 3New York-Presbyterian Hospital, 4Alta Bates
Cancer Center, 5University of Pennsylvania Cancer Center, 6Hospital Claude Huriez, 7Hotel Dieu Hospital,
8Hadassah University Hospital, 9Emory University, 10Universitatsklinikum Heidelberg, 11Princess Margaret
Hospital, 12Hospital Universitario de Salamanca, 13Universitario de Barcelona 14Università di Torino,
15St. Bartholomew's Hospital, 16H. Lee Moffitt Cancer Center, 17Millennium Pharmaceuticals, Inc.
Treatment Plan
Randomization
Bortezomib
Dexamethasone
8 cycles
4 cycles
1.3 mg/m2 IV push
40 mg PO
D 1, 4, 8, 11 q 3-wk cycle
D 1­4, 9­12, 17­20 q 5-wk cycle
3 cycles
5 cycles
1.3 mg/m2 IV push
40 mg PO
D 1, 8, 15, 22 q 5-wk cycle
D 1­4 q 4-wk cycle
273 treatment days
280 treatment days
Time to Progression (N = 669)
78% improvement in median TTP with bortezomib
Median TTP: Bortezomib 6.2 mos
Dexamethasone 3.5 mos
Response Rates (CR, PR)
100
Median TTR
90
- 43 d in both arms
80
DOR
P < 0.0001
70
%
- Bortezomib 8.0 mos vs
60
dex 5.6 mos
50
- Median follow-up ~8.3 mos
38%
40
Response, 30
25% PR
18%
20
< 1% nCR
10
7% nCR
16% PR
< 1% CR
6% CR
0
Bortezomib
Dexamethasone
1-Year Survival, N = 669
80%
66%
41% decreased risk of death with bortezomib
Conclusions
Bortezomib demonstrated superior efficacy to high-dose dex in
relapsed MM
· Significant TTP benefit (P < 0.0001)
­ 78% increase in median TTP
· Response rate advantage (P < 0.0001)
­ 38% vs 18% (CR, PR)
­ 13% vs 2% (CR, nCR)
· Superior overall and 1-yr survival
­ HR = 0.57, P = 0.0013, and HR = 0.53, P = 0.0005
Conclusions (cont.)
As second-line therapy, bortezomib demonstrated
superior efficacy to high-dose dex
· Statistically significant TTP benefit
· Response rate superior
· Survival advantage
Adverse events with bortezomib were manageable
and predictable favorable risk-benefit ratio

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