Myeloma: Standard Front-line Therapy
S. Vincent Rajkumar
Pf
Professor f
o Medi
dicine
Mayo Clinic
Scottsdale, Arizona
Arizona
Rochester,
Rochester Minnesota
M
Minnesota
Jacksonville, Florida
F
Florida
Mayo Clinic College of Medicine
Mayo Clinic Comprehensive Cancer Center
Survival in Myeloma
2-yr
Regim
eg
en
Surviv
Su
al
rate
MP
60%
MPT
>75%
Thal/Dex or VAD:
>80%
Transplant
VMP, Rev/Dex, MPR
>85%
*Lacy et al. 88% survival at 3 years
Rajkumar, 2008
www.msmart.org
Staging and Prognostic Factors
Staging
Prognostic Factors
Factors
Dlt
Dele i
tion 17
17p
t(4;14)
t(14;16)
Durie-Salmon Staging
Deletion 13
International Staging System
Hypodiploidy
Labeling Index >3%
Greipp, 2006
Dispenzieri, 2007
3 Key Questions before Decidi
iding I i
n tial Therapy
· Ii
Is t
it really
l?
myeloma?
· Is there a clinical trial that would be appropriate?
· Am I a transplant candidate?
Rajkumar, 2008
Kyle, R. A. and Rajkumar S. V. Blood 2008;111:2962-2972
www.msmart.org
Ah
Approach to T
t
rea ment: Off
Off St
Study
Newly Diagnosed MM
Not Candidate for Transplant
Transplant Candidate
Standard Chemotherapy
Induction therapy
Transplant
Standard Chemotherapy for
for Patients who
are not Candidates for Transplant
Regimen
Response
CR plus
2 year
rate
VGPR rate
survival rate
MP
50%
10%
65%
MPT
76%
47%
83%
VMP
71%
45%
83%
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Ah
Approach to Initi
iti l
a Treatment
Newly Diagnosed MM
Not Candidate for Transplant
Transplant Candidate
MPT or VMP
Induction therapy
Transplant
Dispenzieri, 2008
Choice of Initi
itial Th
Therapy
Non-Transplant Candidates
Significant
Use in
Neuropathy
Renal
Regimen
Route
DVT Risk
risk
Failure
MPT
Oral
Yes
Yes
Yes
VMP
IV
No
Yes
Yes
Rajkumar SV. ASH 2007
Standard Chemotherapy for Patients who are not
Cd
Can id
didates for Transplant
Regimen (Study)
Response
CR+VGPR
rate
Dex
45%
16%
VAD
63%
19%
Thal Dex
65%
44%
Rev Low dose dex
70%
42%
Vel
Ve Dex
Dex
80%
47%
VTD
85%
60%
Primary Study Results
RD
Rd
Fisher's
N=214
N=207
Exact
p-value
Primary endpoint
Overall response at 4 cycles
79%
69%
0.020
% successful
successful mobilization (n=163)
(n=163)
96%
99%
Overall survival
1-
1 year
88%
96%
0.005
2-year
78%
88%
0.007
Rajkumar SV. ASCO 2008
www.msmart.org
Ah
Approach to Initi
iti l
a Treatment
Newly Diagnosed MM
Not Candidate for Transplant
Transplant Candidate
MPT or VMP
Rev/low-dose Dex or Vel/Dex
Transplant
Dispenzieri, 2008
www.msmart.org
Ah
Approach to Initi
iti l
a Treatment
Newly Diagnosed MM
Not Candidate for Transplant
Transplant Candidate
MPT or VMP
Rev/low-dose Dex or Vel/Dex
Stem Cell Collection
Continue treatment
Transplant;
and
(Second transplant
Delayed Transplant
For some patients)
Dispenzieri, 2008
Choice of Initi
itial Th
Therapy
Transplant Candidates
Significant
Use in
Regimen
Route
DVT Risk
Neuropathy
Renal
risk
Failure
Rev/Dex
Oral
Yes
No
No
Ve
V l/Dex
IV
No
Yes
Yes
Bortezomib
Depends on
containing
IV
specific
Yes
Yes
combinations (eg
(g.,
regimen
VTD, CBD)
Thal/Dex
Oral
Yes
Yes
Yes
Rajkumar SV. ASH 2007
St
Suppor i
tive Care
· Pi
Pam d
id
t
rona e (A
(A
d
re i
di )
a or Z l
o d
e ronic acid
id (Z
(Zometa)
· Antibiotics
· Blood thinners
· Antacids
· Pain meds
· Kyphoplasty or Vertebroplasty
· Radiation
Ei
Emerging Opti
tions for New MM
MM
Tl
Transpl
t
an C
d
an id
did t
a es
· VRd (Richardson)
Non-transplant Candidates
· MPR (Palumbo)
OR
Open Randomi
d
ze T i
r als for New MM
MM
Tl
Transpl
t
an C
d
an id
did t
a es
· SWOG S0777:
Rd vs VRd
· ECOG E1A05:
Vd vs VRd
· Evolution:
VRd vs CVRd vs CVd
Non-transplant Candidates
· ECOG E1A06:
MPT vs MPR
· MM 020:
MPT vs Rd (18 mo) vs Rd (indef)