Phase III

*Facon, 2004 (ASH 206)⁷⁸

Quality*

Up to 400 mg
MP vs. MPT vs. MEL100:

Arm A=Standard MP (assumed—exact MP regimen not stated: melphalan 4 mg/m² po d1-7; prednisone 40 mg/m² d1-7 q6 wk x 12)

Arm B=MPT=same MP + Thal up to 400 mg

Arm C=MEL100=VAD x 2 + melphalan 100 mg/m² iv x 2 (w/ cyclophosphamide 3g/m² for stem cell collection)
[12 mos]

200—Enrollment ongoing (goal N=500)

Inclusion=age 65-75 yr
Actual age & gender of enrolled pts=NS

200

Not reported

Planned interim analysis at N=200 for safety

Shows no clear advantage or disadvantage of either MP-Thal or MEL100 over MP.

*Palumbo, 2004 (ASH 207)⁷⁹

Quality*

100 mg
MPT vs. MP:
melphalan 4 mg/m² po + prednisone 40 mg/m² d1-7 q mo ±Thalidomide 100 mg
Not randomized
enoxaparin prophylaxis added after trial started
[15 mo]

200—Enrollment appears complete
72 yr (56-85)

Gender not specified
Newly diagnosed MM
MM characteristics=NS

102 evaluable at time of report

Overall Response (≥25%)=UTD

m protein reduction:
   100%=UTD
   ≥90%=NS
   ≥75%=18%
   ≥50%=UTD
   ≥25-49%=UTD

After MPT:
   CR=25.9%
   Near CR=5.5%
   PR=48.2%

After MP:
   CR=4.2%
   Near CR=0%
   PR=43.6%

EFS @ 26 mos:
   EFS w/MPT=67.8%
   EFS w/MP=32.4%
   p<0.001

OS not reached

Treatment related mortality:
   MPT=5%
   MP=2%

Adverse events:

  DVT: MPT 19%, MP 2%
  Infections (Grade 3/4): MPT 13%, MP 2%
  Neurotoxicity (Grade 1/2): MPT 36%, MP 5%
  Hem. toxicity (Grade 3/4): MPT 23%, MP 28%

Phase II

*Alexanian, 2004 (ASH 210)⁸⁰

Quality*

100-200 mg
VTD: Velcade (Bortezomib) 1.0-1.9 mg/m² d1, 4, 8 & 11
Thal 100-200 mg
Dex 20 mg/m² q4d d1, 9, 17
Repeat VTD q4 wk
[6 mo (2-14)]

25
63 yr (39-81)

Gender not specified
Previously untreated
MM characteristics=NS

Overall Response (≥25%)=UTD

m protein reduction:
   100%=UTD
   ≥90%=NS
   ≥75%=76%
   ≥50%=84%
   ≥25-49%=NS

Median time to remission=0.6 mo (0.3-1.8)

Autologous blood stem cells easily collected in 12 pts who were intensified for a median 3.6 mo after initial therapy

*Chanan-Khan, Miller, McCarthy, Koryzna, et al, 2004 (ASH 3463)⁸¹

Quality*

100-200 mg
VAD d1-4 qmo + Thal 100-200 mg
Repeat q 4wk x 4 cycles
Coumadin 1-2 mg for DVT prophylaxis
[Median f/u=NS]

16
58 yr (46-77)
50% M

>Stage 1
No prior therapy
Stage III=69%

11 evaluable

Overall Response (≥25%)=91%

m protein reduction:
   100%=3%
   ≥90%=NS
   ≥75%=64%
   ≥50%=NS
   ≥25-49%=NS

*Dimopoulos, 2004 (ASH 1482)⁸²

Quality*

300 mg
MDT: Melphalan 8 mg/m² d-4, Dexamethasone 12 mg/m² d1-4, 14-18
Thal 300 mg. d1-4, 14-18
Repeated q5wk x 10 cycles
[15 mo]

43—Enrollment ongoing (goal N=NS)
78 yr (75-85)

No prior therapy
Inclusion=Symptomatic MM with age ≥75 yr
Stage III=58%
Other MM characteristics=NS

43

Overall Response (≥25%)=72%

m protein reduction:
   100%=10%
   ≥90%=NS
   ≥75%=NS
   ≥50%=62%
   ≥25-49%=NS

Median time to PR=2 mo (0-5-5.5)

OS @ 15 mo median f/u=88%

*Hassoun, 2004 (ASH 2409)⁸³

Quality*

AD/TD=Doxorubicin/Dex followed by Thal/Dex
Doxorubicin=9 mg/m² d1-4, Dex=40 mg/d, d1-4, 9-12, 17-20;
Thal=200 mg
Dex as above

38—Enrollment ongoing (goal N=NS)
59 yr (35-82)
58% M

Stage II & III symptomatic MM
MM characteristics=NS

30

Overall Response (≥25%)=86.6%

m protein reduction:
   100%=20%
   ≥90%=26.6%
   ≥75%=NS
   ≥50%=40%
   ≥25-49%=25%

*Klueppelberg, 2004 (ASH 4932)⁸⁴;
*Klueppelberg, 2004 (ASCO 6702)⁸⁵;
*Klueppelberg, 2005 (ASCO 6697)⁸⁶

Quality*

3 reports of ongoing study with increasing enrollment; most data presented here from most recent report with highest n

100 mg
TDZ:
Thal 100 mg + Dex 10-40 mg d1-4, 9-12, 17-20 for 6 mo then d1-4 qmo +zoledronate 4mg qmo
[Mean time on TDZ= 12 mo; 13 pts followed for 12-24 mo]

33
61 yr (43-82)
73% F

Newly diagnosed MM
HIV+=14%
Stage III=69%
Other MM characteristics=NS

29 evaluable

Overall Response (≥25%)=90%

m protein reduction:
   100%=NS
   ≥90%=28%
   ≥75%=%
   ≥50%=34%
   ≥25-49%=28%

Cumulative probability of ≥25% PPR=73% (± 20.6%) within 10 mo

Responses were unaffected to HIV status or antiviral treatment

Median time to response=5.9 mo

Age-adjusted 1-year OS=74$

Schutt, 2005⁸⁷

Quality 5/5

200-400 mg
Thal-VED: Thal starting at 200 mg and increasing to 400 mg/d + vincristine 1.5 mg d1 + epirubicin 30mg/m²/d d1-2 + Dex 20 mg/m²/d d1-5
Repeated q3wk
Mean # cycles=4 (1-8)
[Median f/u=NS]

31
57 yr (32-77)
68% M

Untreated MM
Stage III=91%
IgG=58%
IgA=19%
B-J protein=16%
Non-secretory=7%

31

Overall Response (≥25%)=80%

m protein reduction:
   100%=19%
   ≥90%=NS
   ≥75%=NS
   ≥50%=61%
   ≥25-49%=NS

EFS @ 36mo=26%

OS @ 36 mo=62%

Med EFS=36 mo

Med OS not reached at 40 mo

Max response to treatment achieved by median 2.8 mo (1.4-7.2 mo)

20 were candidates for SCT and PBSC were collected In all

Zervas, 2004⁸⁸

Quality 3/5

200 mg
+ VAD + Dex 40 mg/m² x 4d on d15 of cycle 1 only
VAD: VCR 2mg Liposomal doxorubicin 40 mg/m²
Dex 40 mg/m² qdx4
[10 mo, 2-22]

39
68 yr (43-75)
51% M

Newly diagnosed with symptomatic MM,
Stage III=64%
IgG=56.5%
IgA=28%
Light chain=13%

39

Overall Response (≥25%)=82%

m protein reduction:
   100%=10%
   ≥90%=NS
   ≥75%=NS
   ≥50%=64%
   ≥25-49%=8%

EFS @ 22 mo=55%

OS @ 22 mo=74%

6 Early deaths:
   4=disease progression
   2=neutropenic infection

38% proceeded to SCT (47% of responders)