A Randomized Phase III Trial of Thalidomide Plus Dexamethasone Versus
Dexamethasone in Newly Diagnosed Multiple Myeloma (E1A00)
E1A00: 207 patients
R
A
N
Off Rx @ 4
D
Thal + Dex
CR/PR/
months-
O
x4 cycles
Stable
for transplant*
M
I
Z
A
Dex
Prog
Off Rx
T
x 4 cycles
anytime
I
O
N
*Treatment beyond 4 cycles was permitted at physician discretion
S. V. Rajkumar et al. Proc ASCO 2004
Dose
Arm A
Arm B
· Thal 200 mg PO daily plus
· Dex 40 mg day 1-4, 9-12,
Dex 40 mg day 1-4, 9-12,
17-20
17-20
All pts received pamidronate or zoledronic acid monthly
S. V. Rajkumar et al. Proc ASCO 2004
Results
Best Response within 4 Cycles using ECOG criteria
· Thal/Dex: 58/98 pts (59%)
1-sided
p-value=0.011*
· Dex:
40/98 pts (41%)
S. V. Rajkumar et al. Proc ASCO 2004
Results
Best Response* within 4 Cycles
· Thal/Dex: 67/98 pts (68%)
· Dex:
46/98 pts (46%)
*allowing for using serum M protein levels in patients in whom
measurable urine M protein was unavailable at follow-up
S. V. Rajkumar et al. Proc ASCO 2004
Major Toxicities Within 4 Cycles
Toxicity
Thal/Dex
Dex
(N=102)
(N=101)
DVT (Grade >=3)
16 (16%)
3 (3%)
Rash (Grade >=3)
4 (4%)
0 (0%)
Sinus bradycardia (Grade >=3)
1 (1%)
0 (0%)
Neuropathy (Grade >=3)
6 (6%)
4 (4%)
Toxicity of Any Type (Grade >=4)
34 (33%)
16 (15%)
Total **
45 (44%)
19 (19%)
** Rows do not add to total as patients could have more than one of
these toxicity
types
S. V. Rajkumar et al. Proc ASCO 2004
Conclusions
· Thal/Dex is an effective induction therapy in newly
diagnosed multiple myeloma
· Response rates with Thal/Dex are superior to Dex
alone but the risk of added toxicity is higher
· Risks/Benefits need to be balanced when deciding
on therapy
Conclusions
· Given these results there is little reason to use
VAD as initial treatment for myeloma
· DVT prophylaxis needed while using Thal/Dex
· Future trials of front-line therapy using more
aggressive oral/intravenous therapy need to show
significant superiority over Thal/dex in randomized
trials
· Future ECOG strategy: Phase III with CC-
5013+Dex (E4A03)