Prognostic Value of Stringent Complete Response Post-Autologous Stem Cell Transplantation in Multiple Myeloma
Prashant Kapoor, MD, Shaji Kumar, MD, Angela Dispenzieri, MD, Martha Q. Lacy, MD, Suzanne R. Hayman, MD, Francis K. Buadi, MD, David Dingli, MD, PhD, Philip R. Greipp, MD,
S. Vincent Rajkumar, MD and Morie A. Gertz, MD, Mayo Clinic, Rochester, MN
BACKGROUND
METHODS
RESULTS
TABLES
KAPLAN-MEIER SURVIVAL CURVES
DISCUSSION
The measurement of serum
Patients' Characteristics
468 patients with MM who had achieved
Gender Male: Female
1.3:1
immunoglobulin free light chains
1.0
In MM, the significance of achieving responses deeper
Out of 468 patients, a total of 179
at least a partial response (PR) after first
Age (years) median (range)
61 (33-76)
Serum M-spike (g/dL), median (range)
0.3 (0-6.9)
Time To Progression (TTP)
than the traditionally defined CR is not well known.
(FLC) has diagnostic and
patients had achieved varying degrees
SCT between September 2002 and
on 0.9
n=178
prognostic utility in multiple
Pre-transplant creatinine <1.5 mg/dL
89%
of CR as their best response.
September 2007 were evaluated.
ssi 0.8
n=179
Strategies focussing on obtaining deep responses
re
myeloma (MM).
Pre-transplant PCLI (%) median (range)
0 (0-9.6)
0.7
have been questioned because attainment of CR has
39, 35 and 105 patients achieved nCR,
og
The individual patient data of serum and
n=177
Pre-transplant LDH (U/L) median (range)
188 (2.97-407)
pr 0.6
incongruously translated into improved OS in MM.
Normalization of the FLC ratio in
CR and sCR, respectively.
urine protein electrophoresis,
P<0.0001
n=177
patients achieving CR may define a
Pre-transplant CRP (mg/dL) median (range) n=178
0.5 (0.015-10.50)
0.5
immunofixation, serum FLC assay, and
The baseline characteristics, laboratory
Bone disease
155 (87%)
Non uniformity of response assessment and reporting
ithout
deeper response after therapy than
BM biopsy and aspiration obtained 60
n=179
0.4
w
sCR
in myeloma-related trials has led to the proposal of
features and the induction
Pre-transplant ISS (n=177)
obtained by the standard criteria of
n
days after the SCT were abstracted to
1
95 (54%)
o 0.3
international uniform response criteria by the
chemotherapy-related information of
ti
CR alone.
2
60 (34%)
determine the best response.
or 0.2
3
22 (12%)
International Myeloma Working Group (IMWG).
the patients are outlined in the tables.
nCR
Pre-transplant Durie-Salmon Stage (n=175)
op
CR
A stringent CR (sCR) requires
0.1
Only patients achieving CR (negative
1a
1 (01%)
Pr
Our analysis focuses on the outcome of patients
The median estimated follow-up for the
2a
58 (33%)
normalization of the FLC ratio and
0.0
serum and urine immunofixation studies,
2b
4 (02%)
achieving varying degrees of CR, and particularly
entire cohort was 52 months from the
absence of clonal plasma cells in
3a
103 (59%)
0
10
20
30
40
50
60
70
disappearance of plasmacytomas with
3b
9 (05%)
highlights the significance of attaining sCR in MM.
diagnosis, and 41 months from SCT.
the bone marrow (BM) in addition
Pre-transplant Ploidy status n=178
Time from transplant (months)
less than 5% BM plasma cells) were
Normal
155 (87%)
to the standard criteria for CR.
The median TTP was 15, 29 and 35
analyzed further for our study. The
Aneuploidy
23(13%)
months for the patients achieving nCR,
CONCLUSIONS
patients attaining CR were parsed into 3
Creation of a more rigorous
CR and sCR, respectively (P<0.0001).
sub-categories: nCR, CR and sCR, using
category of CR requires validation
sCR
Overall Survival
FLC ratio & immunohistochemistry.
Therapy-Related Information
since it is not known whether the
The median OS for patients achieving
0.9
First Induction Regimen (n=179)
sCR represents a deeper response state compared to
CR
achievement of sCR translates into
nCR was 53 months from the diagnosis,
0.8
OS and TTP ( time from SCT to
i) Thalidomide-dexamethasone
66 (37%)
g
conventional CR, translating to a longer response
better clinical outcome.
ii) Dexamethasone
52 (29%)
but not reached for those achieving CR
in
progression, with non-myeloma related
0.7
iii) Vincristine, adriamycin dexamethasone (VAD)
27 (15%)
duration post-SCT, validating its inclusion in the
iv
iv) Lenalidomide-dexamethasone
21 (12%)
or sCR (P=0.0009). Please refer to the
deaths censored) were estimated by
rv
v) Bortezomib-dexamethasone
4 (2%)
0.6
modified IMWG uniform response criteria.
u
vi) Bortezomib, thalidomide-dexamethasone (VTD)
3 (2%)
Kaplan- Meier survival curves.
OBJECTIVE
Kaplan-Meier method and compared by
S
vii) Vincristine, carmustine, melphalan,
n 0.5
While we did not see a significant improvement in OS
cyclophosphamide, prednisone (VBMCP)
2 (1%)
o
log-rank tests.
viii) Melphalan-dexamethasone (MP)
2 (1%)
The 5-year OS was 80% and 79% for
ti 0.4
nCR
with achievement of sCR compared with CR in our
To evaluate the impact of specific
ix) Other therapies
2 (1%)
or
patients with CR and sCR, respectively
P=0.0009
Immunohistochemical studies with
op 0.3
cohort, this question needs to be addressed in a larger
types of CR [sCR, CR or near CR
Novel agent-based therapy
94 (52.5%)
(P=NS).
Pr
antibodies to kappa and lambda light
study.
(nCR/ immunofixation positive CR)]
Response to induction therapy (n=179)
167 (93%)
0.2
chains were performed on BM. In
post-stem cell transplantation
Conditioning regimens (n=179)
OS from SCT was also significantly
0.1
A step-wise improvement in the response duration
addition, clonality of plasma cells was
(SCT) on time to progression (TTP)
i) Carmustine, etoposide, cytarabine and melphalan
shorter in patients achieving nCR (42
0.0
across nCR, CR and sCR highlights the contribution of
(BEAM)
1 (1%)
assessed with the slide-based plasma
and overall survival (OS) of patients
ii) Melphalan 140mg/m2
21 (12%)
months vs. not reached for patients in
0
10 20 30 40 50 60 70 80 90 100
120
140
immunofixation studies, marrow assessment of
iii) Melphalan 200mg/m2
152 (85%)
cell labeling index method.
with newly diagnosed MM.
iv) Ibritumomab-melphalan
5 (3%)
CR and sCR; P<0.001).
Follow-up from diagnosis (months)
clonality and serum FLC estimates.

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