How I Treat Myeloma: Transplant Ineligible Patient
S. Vincent Rajkumar
Professor of Medicine
Mayo Clinic
Scottsdale, Arizona
Rochester, Minnesota
Jacksonville, Florida
Mayo Clinic College of Medicine
Mayo Clinic Comprehensive Cancer Center
· No conflicts to disclose
Rajkumar SV. 2011
How I Treat
Transplant Ineligible Newly Diagnosed MM
High Risk
Intermediate Risk
Standard Risk
New MM
· No melphalan
· No thalidomide
· No high-dose dex
· No twice-weekly or IV bortezomib
· Target CR only in high risk
Rajkumar SV. 2011
© Remstein E, Jevremovic D. 2010
MGUS
SMM
MM
Monoclonal
Protein
Bone
<10% plasma cells
10% plasma
10% plasma
Marrow/ M
AND <3gm/dL M
cells OR 3 gm/dL
cells
Protein
protein
M protein
Clinical
Asymptomatic
Asymptomatic
Symptomatic
Picture
No end-organ damage*
No end-organ damage
End-organ damage present
Therapy
Observation only
Observation only
Therapy required
*Hypercalcemia, anemia, renal failure or lytic bone lesions attributable to plasma cell disorder
Kyle RA. N Engl J Med June 21, 2007
Rajkumar SV. Cecil Textbook of Medicine, 24th Edition (In press)
msmart.org
mSMART 2.0 Risk Stratification
High-Risk
Intermediate-Risk
Standard-Risk
FISH
FISH
All others including:
Del 17p
t(4;14)
t(14;16)
Hyperdiploid
t(14;20)
Cytogenetic
t(11;14)
Deletion 13 or
t(6;14)
GEP defined high-
hypodiploidy
risk
PCLI >3%
MP: No longer an option
42% 3 yr survival rate in a meta analysis of 26 trials
MTCG. J Clin Oncol 1998; 16:3832
What are the current options?
Rajkumar SV. 2011
Alkylator-Steroid + IMiD
· MPT
· MPR
· CTD
· CRD
Rajkumar SV. 2011
Treatment of elderly MM patients (MPT vs MP)
TTP
Overall
3 year OS
Study
Regimen
N
Survival
PFS/EFS
(months)
(%)
Palumbo
MPT
129
22
45 vs 48
~65% (MPT)
(Blood 2008)
MP
126
15
P=0.79
Facon
MPT
125
28
52 vs33
~65% (MPT)
(Lancet 2007)
MP
196
18
P=0.0006
Hulin
MPT
113
24
44 vs 29
~55% (MPT)**
(JCO 2009)
MP
116
19
P=0.03
Wijermans
MPT
165
13
40 vs 31
~55% (MPT)
(JCO 2010)
MP
168
9
P=0.05
Waage
MPT
182
15
29 vs 32
~43% (MPT)
(Blood 2010)
MP
175
14
P=0.46
Beksac
MPT
58
21
26 vs 28
~30% (MPT)
(Eur J
MP
57
14
P=0.65
Hematol 2011)
Rajkumar SV. 2011
Adverse Events with MPT in the Elderly
MP
MPT
Grade 2 neuropathy
5%
21%
Hulin C. J Clin Oncol 2009 Aug 1;27(22):3664-70
MP versus MPR
Med
Me i
d a
i n PF
P S
F
100
MPR
MP -
R R
31 months
R
31 month
MPR
14 months
MPR
14 month
) 75
%
MP
13 months
MP
13 month
(ts
en 50
ati
HR 0.398
P
P < .0000001
25
HR 0.804
P = .153
0 0
5
10
15
20
25
30
35
40
Time (months)
Median follow-up 25 months
*Analysis based on data up to May 2010
1
Palumbo A. ASH 2010
Alkylator-Steroid + Bortezomib
· VMP
· VCD (CyBorD)
Rajkumar SV. 2011
VISTA Trial: VMP vs MP: Overall Survival
San Miguel J et al. N Engl J Med 2008;359:906-917
VISTA TRIAL: Adverse Events (Safety Population)
VMP
MP
San Miguel J et al. N Engl J Med 2008;359:906-917
VMP in High/Intermediate Risk MM
TTP
OS
VMP standard risk
VMP standard risk
VMP high risk
VMP high risk
VMP standard risk (N=142): 23.1 months (34 events)
VMP standard risk (N=142): not reached (16 events)
VMP high risk (N=26): 19.8 months (7 events)
VMP high risk (N=26): not reached (3 events)
HR = 1.297 (95% CI: 0.55, 3.06)
HR = 1.009 (95% CI: 0.278, 3.663)
San Miguel J et al. N Engl J Med 2008;359:906-917
Non-Melphalan Containing Regimens
· Rd
· VRD, VTD, VTP
Rajkumar SV. 2011
Treatment of elderly MM patients (Phase III trials)
TTP
Overall
3 year OS
Study
Regimen
N
Survival
PFS/EFS
(months)
(%)
Palumbo
MPT
129
22
45 vs 48
~60% (MPT)
(Blood 2008)
MP
126
15
P=0.79
Facon
MPT
125
28
52 vs33
~65% (MPT)
(Lancet 2007)
MP
196
18
P=0.0006
Hulin
MPT
113
24
44 vs 29
~55% (MPT)**
(JCO 2009)
MP
116
19
P=0.03
Wijermans
MPT
165
13
40 vs 31
~55% (MPT)
(JCO 2010)
MP
168
9
P=0.05
Waage
MPT
182
15
29 vs 32
~43% (MPT)
(Blood 2010)
MP
175
14
P=0.46
San Miguel
VMP
344
24
NR* vs 43
69% (VMP)
(JCO 2010)
MP
338
17
P<0.001
Rajkumar
Rd
222
25
NR*
75% (Rd age 65)
(Lancet Oncol
RD
223
19
2010)
Rajkumar SV. 2011
Overall survival with Rd in patients 70
3 yr OS
Toxicity
3 yr OS
excluding SCT
Jacobus, EHA
2010
73%
70%
Gay, EHA 2010
70%
65%
Rajkumar SV. Lancet Oncology 2010; Gay F. EHA 2010; Jacobus S. EHA 2010
VRD
· 66 evaluable pts
CR
29%
nCR
11%
67%*
VGPR
27%
PR (33%)
· Overall response rate: 100%
Richardson PG. Blood 2010;116:679-686
VCD (CyBorD)
EVOLUTION
Mayo Clinic
VRD
VCD
VCD
Response, %
(n = 42)
(n = 49)
(n = 63)
CR/nCR
40%
37%
41%
VGPR
50%
45%
60%
ORR ( PR)
83%
84%
90%
Kumar S. ASH 2010; Reeder C. Blood 2010
Choice of Initial Therapy
Non-Transplant Candidates
Regimen
Route
DVT Risk
Neuropathy risk
MPT/CTDa
Oral
Yes
Yes
VMP/VCD
IV
No
Yes
Rd
Oral
Yes
No
VRd, VTD, VTP
IV
Yes
Yes
Rajkumar SV. 2011
How I Treat
Transplant Ineligible Newly Diagnosed MM
High Risk
Intermediate Risk
Standard Risk
?
Need Velcade
Rd
VRd
VCd (CyBorD)
FIRST
Goal: CR
(Weekly, SQ)
TRIAL
MPT vs Rd
Dispenzieri et al. Mayo Clin Proc 2007;82:323-341; Kumar et al. Mayo Clin Proc 2009 84:1095-1110
Adapted from mSMART v7 Revised and updated: Jan 2011
What schedule of bortezomib?
Rajkumar SV. 2011
Excellent results with once-weekly Bortezomib
Mateos M-V. Lancet Oncology Volume 11, Issue 10, October 2010, Pages 934-941
Excellent results with once-weekly Bortezomib
VMP versus VMPT
Palumbo A et al. JCO 2010;28:5101-5109
©2010 by American Society of Clinical Oncology
Excellent results with SQ Bortezomib
Moreau P. 2011. The Lancet Oncology
How long to treat?
Rajkumar SV. 2011
How I Treat
Transplant Ineligible Newly Diagnosed MM
High Risk
Intermediate Risk
Standard Risk
VRd
Vcd
Rd
Goal: CR
1 year
18 months
and then
and then
and then discuss
bortezomib-based maintenance
bortezomib maintenance
lenalidomide maintenance
till progression
for 2 years
Dispenzieri et al. Mayo Clin Proc 2007;82:323-341; Kumar et al. Mayo Clin Proc 2009 84:1095-1110
Adapted from mSMART v7 2011
Acute Renal Failure
Burnette, N Engl J Med 2011
Supportive Care
· Pamidronate (Aredia) or Zoledronic acid (Zometa)
· Antibiotics
· Anticoagulants
· Prevention of gastritis
· Pain control
· Kyphoplasty or Vertebroplasty
· Radiation
The FINAL slide