Novel Agents for Initial Therapy of Multiple
Myeloma: Comparable Results with Continued Initial
Therapy and Delayed Transplantation at Relapse
vs. Early Transplantation
Shaji Kumar, Martha Q. Lacy, Angela Dispenzieri, Francis K.
Buadi, Suzanne R. Hayman, David Dingli, Francesca Gay,
William Hogan, S. Vincent Rajkumar, Morie A Gertz
Mayo Clinic
Scottsdale, Arizona
Rochester, Minnesota
Jacksonville, Florida
Mayo Clinic College of Medicine
Mayo Clinic Comprehensive Cancer Center
Efficacy improvements with novel
induction regimens
(%)
VGPR
with
Patients
Regimen
Cavo M, et al. Blood. 2008;112:[abstract 158]. Harousseau J-L, et al. ASH/ASCO symposium at ASH, 2008. Lokhorst HM, et al. Haematologica. 2008;93:124-7. Macro
M, et al. Blood. 2006;108:[abstract 57]; updated data from ASH 2006. Morgan G, et al. Blood. 2007;110:[abstract 3593]; updated data from ASH 2007. Rajkumar SV, et
al. ASH/ASCO symposium at ASH 2008. Richardson P, et al. Blood. 2008;112:[abstract 92]. Sonneveld P, et al. Blood. 2008;112:[abstract 653].
HDT in MM patients < 55 years old:
up-front or rescue treatment
Early HDT
1.0
1.0
0.8
0.6
probability 0.4
0.8
OS
TWiSTT
EFS
0.2
Survival
0
0.6
0
10 20 30 40 50 60 70 80 90 100
Time (months)
probability
0.4
1.0
Late HDT
0.8
Survival
0.6
0.2
Early HDT
Late HDT
probability 0.4
OS
TWiSTT
0.2
Post-HDT EFS
0
Post-CCT EFS
Survival
TWiSTT
0
20
40
60
80
100
0 0 10 20 30 40 50 60 70 80 90 100
Time (months)
Time (months)
HDT = high-dose therapy; TWiSTT = time without
symptoms, treatment, or treatment toxicity.
Fermand J-P, et al. Blood. 1998;92:3131-6.
Objective
Is continued therapy with novel agents and high
dose therapy with SCT at the time of relapse
comparable to early SCT?
Patients and Methods
· Patients seen at Mayo Clinic between 2001
and 2008
· Received initial therapy with thalidomide-
dexamethasone (TD) or lenalidomide-
dexamethasone (LD) (n=410)
· 290 (71%) patients in whom a stem cell
harvest was attempted (started on growth
factor irrespective of collection success) were
considered transplant eligible for this study
Patients and Methods
Early SCT group (n=173; 60%):
SCT within 12 months of diagnosis
and within 2 months of stem cell
290
harvest
Delayed SCT group (n=117; 40%):
Remaining patients; irrespective of
whether an SCT was actually done
Majority of patients did not get tandem SCT or maintenance therapy
Results
· The median estimated follow up for the entire
group was 40 months from diagnosis
· 35 and 42 months respectively for the early and
delayed groups.
· 45/117 (39%) patients in the delayed group
have been transplanted to date (68 had a
second line therapy)
· The median estimated time to SCT was 5.3
months among the early group compared to
39 months in the delayed group.
Results
· Among the 290 patients initial therapy was:
· Thalidomide - Dex in 123 (43%)
· Lenalidomide - Dex in 167 (57%)
· 82 (67%) patients receiving TD had an early
SCT compared to 91 (55%) patients in the LD
group; P=0.04.
· The median follow up is longer in the TD
group compared to LD (58 vs. 24 months)
Baseline characteristics
Variable
Early SCT
Delayed SCT
P
(n=174)
(n=118)
Age (Diagnosis)
58
61
NS
Gender (Male)
57%
66%
NS
Serum Creatinine (mg/dL)
0.9
1
NS
Beta 2 microglobulin
2.3
2.4
NS
LDH (U/L)
228
185
<
0.001
Marrow plasma cell %
14%
10%
NS
Plasma cell labeling index
0.4%
1%
NS
Best response: Initial therapy
Overall survival from diagnosis
(n=118)
(n=174)
Median OS for early group was 86 mos (95% CI; 80,98) vs. NR (95% CI; 54, NR)
for delayed group (P = 0.3)
Overall survival: By initial therapy
(n=76)
(n=41)
(n=91)
(n=82)
TD
LD
Characteristics at SCT
Variable
Early SCT
Delayed SCT
P
(n=174)
(n=45)
Age
58
62
0.06
Serum Creatinine (mg/dL)
0.9
1
NS
Beta 2 microglobulin
2.2
2.6
NS
LDH (U/L)
180
177
NS
Serum M-Spike (gm/dL)
0.7
0.8
NS
Marrow plasma cell %
7%
10%
NS
Plasma cell labeling index
0.2%
0.5%
0.06
Response at time of SCT
Delayed SCT
· Mel 200 was the conditioning regimen for
nearly all patients
· Post SCT hospitalization days were higher
among delayed SCT group (median 4 vs. 0; P
< 0.01)
· The response rate to SCT was higher among
the early group: 93% vs. 83% (P = 0.049)
Post SCT-TTP
(n=174)
(n=45)
Median TTP post SCT 20 mos for early vs. 16 mos for delayed (P=0.2)
Post-SCT Overall survival
(n=174)
(n=45)
Trend to better OS post SCT for early SCT group, 80 mos vs. 43 mos, P =
0.04 (Breslow Gehan); P = 0.16 (logrank)
Conclusions
· In a group of patients receiving initial therapy
with IMiDs, the overall survival appears to be
comparable, whether an upfront approach or
SCT at relapse is used.
· The time to progression appears comparable
following SCT, likely reflecting lack of alkylator
exposure pre-SCT
· However, OS post SCT appear to be lower for
the delayed SCT group reflecting less options
for salvage therapy (already used up)
Conclusions
· SCT should be considered a "regimen" for
myeloma therapy not a platform to base all
therapy on
· No QOL measurements in this study, but
clearly plays an important role in the decision
making process of "early" vs. "delayed"
· Retrospective nature precludes understanding
reason for early vs. delayed decision and
prospective studies are needed
The Mayo Myeloma Group
Rochester
Tom Witzig, MD
Vince Rajkumar, MD
S Zeldenrust, MD, PhD
Francis Buadi, MD
David Dingli, MD, PhD
Matthew Drake, MD, PhD
Arizona
Kristen Short-Detweiler, NP
Leif Bergsagel, MD
Morie Gertz, MD
Rafael Fonseca, MD
Phil Greipp, MD
Joseph Mikhael, MD
Suzanne Hayman, MD
Craig Reeder, MD
Shaji Kumar, MD
Keith Stewart, MD
Robert Kyle, MD
Martha Lacy, MD
Nelson Leung, MD
John Lust, MD
Jacksonville
Greg Nowakowski, MD
Vivek Roy, MD
Steve Russell, MD, PhD
http://msmart.org/