Improving Survival in Multiple Myeloma: Impact of Novel Therapies
Shaji K. Kumar, M.D, S. Vincent Rajkumar, M.D, Angela Dispenzieri, M.D, Martha Q. Lacy, M.D, Suzanne R. Hayman, M.D, Francis K. Buadi, M.D, Steven R. Zeldenrust, M.D,
David Dingli, M.D, Ph.D., Stephen J. Russell, M.D, John A. Lust, M.D, Philip R. Greipp, M.D, Robert A. Kyle, M.D, Morie A. Gertz, M.D.
Mayo Clinic, Rochester, MN 55905
Background
Results and Discussion
·Among patients relapsing after HDT, there were 245 males (63%); median (range) age at transplant was 57 years (33-75) and the median
Recent advances in the therapy of multiple
time to transplant was 8 months (1-90 months) from diagnosis.
myeloma (MM) have increased the treatment
·141 (36%) were alive at the time of analysis and the median follow up for these patients were 47 months (8-145 months) from transplant and
options
for
this
uniformly
fatal
plasma
cell
21 months (0-86 months) from post-transplant relapse respectively.
malignancy. It is not clear if introduction of novel
· 98 relapses (25%) were prior to Dec 31, 2000 and the rest after this date. The median OS from relapse was 12 months (95% CI; 8.7, 14.9)
therapies and the increased use of high dose
for those relapsing before 2000 compared to 24 months (95% CI; 19.8, 27.6) for the rest.
therapy (HDT) in the past decade have translated
· In a multivariate analysis, this difference in survival was independent of the disease status at time of ASCT (in response, primary refractory
into better outcome for patients (pts) with MM.
or in relapse), timing of SCT (early versus late), number of treatment regimens prior to SCT, as well as the response duration to the transplant.
·Among this patient group, 161 (41%) had at some point after their relapse received bortezomib, thalidomide or lenalidomide. These included
Patients and Methods
69, 111 and 36 patients each who had treatment with bortezomib, thalidomide or lenalidomide respectively. The median overall survival for the
161 patients was 31 months (95% CI; 23.6, 38.2) compared to 15 months (95% CI; 11.3, 18.4); p<0.001) for patients not treated with the novel
We examined the outcome of two cohorts of
agents (Figure 1A, B)
patients seen at our institution. The first cohort
1A
1B
· Among newly diagnosed MM, the median age at diagnosis
consisted of 387 patients who relapsed after HDT
1.0
1.0
was 66 years (21­97 years), and 1,770 (59%) were males.
and was examined for potential improvement in
R elaps ed before 1998
· 1051 patients (35%) were diagnosed during the past
survival
following
relapse
after
HDT.
These
R elaps ed 1998-99
0.8
0.8
R elaps ed 20 00-01
E x pos ed to new drug s
decade and rest were diagnosed prior to December 1996. The
patients were divided into two groups; those who
R elaps ed 2002-03
g
N o E x pos ure to new drug s
in
ng
iv
iv
R elaps ed 2004-05
rv
0.6
rv
median survival for those diagnosed in the last decade was 45
relapsed before or after December 31, 2000. The
u
u
0.6
s
sn
ion
months (95% CI; 39.6, 50) compared to 30 months (95% CI;
second cohort consisted of 2981 patients with
rt
rtio
ropo
0.4
ropo
0.4
28.3, 31.6); p<0.001 for those diagnosed earlier (Figure 2A).
newly diagnosed MM seen between January 1971
P
P
· This improved survival was seen in every ISS stage with 5-
and December 2006 and was used to examine
0.2
0.2
year survival estimates for the later group compared to the
the trends in overall survival (OS).
earlier group being 52% vs. 37%, 42% vs. 28% and 28% vs.
0.0
0.0
0
20406 080
100
0
2 04 06 08 0
1 0 0
14% for ISS stages I, II and III respectively (p < 0.01).
Summary and Conclusion
T im e from pos t A S C T rela p se (m onths )
Tim e fro m p os t-A S C T re la p se (m o nths )
2A
· We also divided the patients into 6 groups, each diagnosed
2B
In
conclusion,
we
demonstrate
a
clear
cut
1.0
1.0
over a 6-year interval. While no change was seen in survival
1971-76
improvement in the outcome of patients with
during the first 4 six-year periods, a significant improvement in
197 7-82
0.8
0.8
1983-88
myeloma in the last decade. In our study we
survival was seen during the past 6 years (Figure 2B).
1989-94
g
D iagnos is after 199 6
in
believe that HDT and supportive care were
1994-00
iv
· We also examined the impact of age and gender on the
v
0.6
l
0.6
ur
D iagno sis during/be fore 1996
a
2001-06
s
iv
responsible for the trends seen during 1994-2000
survival trends. The median overall survival was significantly
on
rv
ti
Su
and this along with the novel drugs contributed to
por
0.4
better for patients 65 or less at the time of diagnosis (42 mos
ro
0.4
P
the striking improvement seen since 2000. It also
vs. 28 mos, p<0.001). The improvement in survival seen in
0.2
0.2
highlights the need to target the older patient
the last decade among newly diagnosed patients was
population for innovative approaches in order to
predominantly among those younger than 65 years (60 mos
0.0
0.0
improve outcome in these patients.
0
20
40
60
8 0
100
120
140
0
2 04 06 08 0
1 0 0
1 2 0
1 4 0
vs. 33. mos) compared to older patients (32 mos vs. 27mos).
T im e from diag no sis (m on th s)
Tim e

Document Outline