Bone Marrow Transplantation (2009) 43, 793–800
& 2009 Macmillan Publishers Limited All rights reserved 0268-3369/09 $32.00
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ORIGINAL ARTICLE
Bortezomib administered pre-auto-SCT and as maintenance therapy
post transplant for multiple myeloma: a single institution phase II study
GL Uy, SD Goyal, NM Fisher, AY Oza, MH Tomasson, K Stockerl-Goldstein, JF DiPersio and R Vij
Division of Oncology, Section of Bone Marrow Transplantation and Leukemia, Washington University School of Medicine,
St Louis, MO, USA
The appropriate induction therapy before and the role of
maintenance therapy after auto-SCT for patients with
multiple myeloma remain areas of active investigation.
We conducted a study in 40 patients with bortezomib
given sequentially pre-auto-SCT and as maintenance
therapy post auto-SCT. Pre-transplant bortezomib was
administered for two cycles followed by high-dose
melphalan 200 mg/m2 with auto-SCT of G-CSF-mobilized
PBMCs. Post transplant bortezomib was administered
weekly for 5 out of 6 weeks for six cycles. No adverse
effects were observed on stem cell mobilization or
engraftment. An overall response rate of 83% with a
CR þ very good partial remission (VGPR) of 50% was
observed with this approach. Three-year Kaplan–Meier
estimates of disease-free survival and overall survival (OS)
were 38.2 and 63.1%, respectively. Bortezomib reduced
CD8 þ cytotoxic T cell and CD56 þ natural killer cell
PBL subsets and was clinically associated with high rates
of viral reactivation to varicella zoster.
Bone Marrow Transplantation (2009) 43, 793–800;
doi:10.1038/bmt.2008.384; published online 24 November 2008
Keywords: auto-SCT; stem cell mobilization; multiple
myeloma; bortezomib
Introduction
The role of high-dose chemotherapy (HDCT) with autoSCT in the treatment of multiple myeloma was established
by the IFM90 and MRC VII studies, which showed the
superiority of this approach over conventional cytotoxic
chemotherapy.1,2 Although improvements in disease-free
and overall survival (OS) are observed with auto-SCT, the
majority of patients relapse within 3 years of therapy and
few, if any, patients are cured of their disease. As a result,
there is a great interest in developing therapeutic strategies
that can further improve outcomes. In recent years,
Correspondence: Dr GL Uy, Section of Bone Marrow Transplant and
Leukemia, Washington University School of Medicine, 660 S. Euclid
Ave., Campus Box 8007, St Louis, MO 63110, USA.
E-mail: [email protected]
Received 12 June 2008; revised 6 August 2008; accepted 9 August 2008;
published online 24 November 2008
regimens using the proteasome inhibitor bortezomib and
immunomodulatory drugs have shown impressive response
rates in patients with relapsed or refractory multiple
myeloma.3–6 Yet questions remain on how to integrate
these newer anti-myeloma agents into the transplant
paradigm.
Bortezomib has been used either alone or in novel
combinations during pre-auto-SCT induction therapy to
improve complete and overall response rates.7–10 However,
no study has reported on the use of bortezomib maintenance therapy after HDCT. In the present trial, we
sought to test the safety and efficacy of an approach in
which bortezomib is administered sequentially before
HDCT and also as maintenance therapy after transplant.
Because of the potential immunomodulatory effects of
bortezomib, we also conducted exploratory studies on PBL
subsets during bortezomib therapy.
Methods
Patients
Patients diagnosed with multiple myeloma were enrolled in
this trial before treatment with HDCT and auto-SCT at the
Washington University School of Medicine. Patients
received induction therapy at the discretion of the referring
oncologist. Patient’s age X18 years, ECOG/Zubrod
performance status p2, and acceptable baseline organ
function (platelets 4100 000/mm3, hemoglobin 48 g/
100 ml, ANC 41500/mm3, AST, ALT p3 ULN, total
bilirubin p2 upper limit of normal, and creatinine
clearance X20 ml/min) were eligible for the study. Individuals with amyloidosis, peripheral neuropathy XNCI
grade 2 or those treated earlier with 45 cycles of an
anthracycline or 41 cycle of high-dose CY or other
alkylator-based regimen were excluded. This study was
approved by the Institutional Review Board of Washington
University with all patients providing informed consent
according to institutional standards before treatment.
Study design and treatment schedule
After induction chemotherapy, two cycles of bortezomib
1.3 mg/m2/day were administered by i.v. infusion on days 1,
4, 8 and 11 of a 28-day cycle (Figure 1). On cycle 2, day 21
of therapy, patients were initiated on G-CSF 10 mg/k 5
Bortezomib pre- and post transplant
GL Uy et al
794
Pre-transplant
Bortezomib 1.3 mg/m2
Days 1, 4
Days 1, 4
Days 8, 11
G-CSF
10 mcg/kg/day
Days 8, 11
CYCLE 1
CYCLE 2
Apheresis
20 L / day
Transplant
Melphalan 100 mg/m2/day
GM-CSF 250 mcg/m2/day until
ANC 1,500/mm 3 x 2 days
Days -3, -2
Days +90 to 120
Day 0
Stem cell infusion
Post transplant
Days +90 to 120 Week 5
CYCLE 1
Bortezomib 1.3 mg/m2
Days 1, 8, 15, 22 of 35 - day cycle x 6 cycles
Week 10
CYCLE 2
Week 20
Week 15
CYCLE 3
CYCLE 4
CYCLE 5
Off study
Week 25
Week 30 Week 33
CYCLE 6
Response evaluation
Lymphocyte subsets
Schema (a) Pre-transplant bortezomib followed by G-CSF mobilization and harvest of PBSCs. (b) High-dose melphalan 200 mg/m2 with
auto-SCT. (c) Post transplant maintenance/consolidation bortezomib.
Figure 1
days that was continued until completion of harvest for
mobilization of stem cells. Stem cells were collected by large
volume apheresis (20 l/day) until a target of 2.5 106
CD34 þ cells/kg recipient body weight was achieved.
Thereafter, patients were conditioned with high-dose
melphalan 100 mg/m2/day 2 days followed by reinfusion
of PBSCs. GM-CSF 250 mg/m2 was administered post
transplant until neutrophil engraftment. Beginning at
90–120 days post transplant, maintenance therapy consisting
of bortezomib 1.3 mg/m2 was administered weekly for 4 of
every 5 weeks for up to six cycles. Responses were assessed
according to the International Uniform Response Criteria.11 Toxicities were graded according to the National
Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)H v3.0.12 Antiviral prophylaxis
was administered until neutrophil engraftment.
CD34 and lymphocyte subset analysis
CD34 þ cells were enumerated using a single platform, lyse,
no wash system according to International Society of
Hematotherapy and Graft Engineering protocols.13 Peripheral blood was collected at baseline (cycle 1, day 1) and
after two cycles of pre-transplant bortezomib (cycle 2,
day 21) for lymphocyte subset analysis by multicolor
Bone Marrow Transplantation
flow cytometry (FC500, Beckman Coulter) gated on the
CD45bright, side scatterlow population.
End points and statistics
The primary objective was to study the effect of bortezomib
administered before stem cell mobilization on the yield of
CD34 þ stem cells in the first apheresis product. Secondary
objectives were to (i) evaluate the time to PFS and diseasefree survival for these patients who also received bortezomib after auto-SCT, (ii) evaluate the toxicity of bortezomib
used before mobilization and after auto-SCT and (iii)
determine the effects of bortezomib on the content of CD34
and lymphocyte subsets in the peripheral blood. Differences between baseline and post-bortezomib PBL subsets
were analyzed by the Wilcoxon signed-rank test. Response
rates and Kaplan–Meier estimates of EFS and OS were
conducted on an intention-to-treat basis.
Results
Patient population
This study enrolled 40 patients between October 2003 and
March 2005 with symptomatic multiple myeloma deemed
Bortezomib pre- and post transplant
GL Uy et al
795
appropriate for HDCT (Table 1). Of the 40 patients, 38
received induction chemotherapy before their first dose of
bortezomib with the most common induction regimens
Table 1
Patient characteristics at baseline (n ¼ 40)
Variable
Patients
N
Age (years), median (range)
56 (39–69)
Sex
Male
Female
24
16
M-protein type
IgG (k:l)
IgA (k:l)
Light chain (k:l)
29 (17:12)
9 (7:2)
2 (1:1)
Durie–Salmon stage
I (A/B)
II (A/B)
III (A/B)
b-2 microglobulin, median (range)
1
12
27
2.7
(1:0)
(11:1)
(24:3)
(1.4–37.3)
Prior therapy
Number of prior regimens, median (range)
Median time from induction to bortezomib (days)
Steroids (%)
Anthracycline (%)
Vinca alkaloid (%)
Thalidomide (%)
Melphalan (%)
No chemotherapy (%)
Radiation therapy (%)
1
120
38
23
23
20
1
2
3
(0–3)
(0–392)
(95)
(58)
(58)
(50)
(3)
(5)
(8)
40 Patients
enrolled and
received
pre-auto-SCT
bortezomib
being doxorubicin, vincristine and dexamethasone (VAD
or DVd regimen) or thalidomide and dexamethasone.
Treatment with bortezomib began at a median of 120 days
(range 0–392) post-induction chemotherapy. Median time
from diagnosis to the start of induction chemotherapy was
14 days (range 0–44 months).
Pre-transplant bortezomib
Of the 40 enrolled patients, 39 completed two cycles of
pre-transplant bortezomib (Figure 2). One early discontinuation occurred during the first cycle of therapy because
of rapidly progressive disease. One additional patient did
not proceed to stem cell collection because of cerebrovascular ischemia occurring during G-CSF mobilization.
Thirty-one patients had measurable monoclonal protein
levels at diagnosis, before and after pre-transplant bortezomib. For these patients, their M-protein decreased from a
median of 2.6 g/100 ml (range 0–8.45) at the
start of induction, to 1.05 g/100 ml (0–4.8) before pretransplant bortezomib and to 0.85 g/100 ml (0–3.3) after
two cycles of bortezomib. Response assessment immediately before stem cell mobilization showed a CR þ very
good partial remission (VGPR) in six patients (15%) and
partial remission (PR) in another 22 patients (55%). Six
patients (19%) experienced a 475% reduction in monoclonal protein with an additional three patients (10%)
having a 25–75% decrease during their pre-transplant
bortezomib.
1 did not receive transplant due to comorbidities
1 failed to mobilize stem cells before transplant
1 had PD before transplant
37 Patients
received
auto-SCT
1 had PD shortly after transplant
3 could not receive post-auto-SCT bortezomib because of neuropathy
33 patients proceeded
to receive post-auto-SCT
bortezomib
28 patients
completed six full
cycles of post-auto-SCT
bortezomib
Figure 2 Progression of patients through treatment protocol.
Bone Marrow Transplantation
Bortezomib pre- and post transplant
GL Uy et al
796
Survival analysis
The median follow-up of the entire cohort is currently 795
days (range 273–116) with 29 patients alive and 11 patients
Table 2
10
8
6
4
2
e-
te
or
st
-b
bo
rt
ez
om
zo
m
ib
ib
0
Po
Pr
Post transplant bortezomib
Of the 40 enrolled patients, 28 received post transplant
bortezomib. During post transplant bortezomib, the
response of one patient improved from VGPR to CR and
that of an additional patient improved from PR to VGPR.
The median follow-up of the surviving patients is 838 days
(range 550–1116). By intention to treat, a VGPR þ CR rate
of 43% with an overall response rate (PR þ VGPR þ CR)
of 73% was observed with the study protocol. The best
response achieved at any time during the treatment
protocol was CR þ VGPR in 50% and PR in 33%.
Adverse events
The most common adverse events during pre- and post
transplant bortezomib were grade 1 fatigue in 17/40 (43%)
patients and grades 1–2 pain in 18/40 (45%) patients.
Twenty-one patients (53%) experienced neuropathy during
the study protocol including five (13%) patients with grades
3–4 neuropathy. Treatment-emergent neuropathy occurred
in three (8%) patients during the pre-transplant phase and
four (10%) patients during the post transplant bortezomib
(Table 4). Of those experiencing treatment-emergent
Ba
se
lin
e
Stem cell collection and HDCT
The successful collection of 2.5 106 CD34 þ /kg G-CSFmobilized PBSCs was achieved in 37 of 38 patients. Twentynine (76%) patients required a single day for collection and in
36 patients (95%) collection was completed within 2 days,
with a median first collection of 4.24 106 CD34 þ /kg
(Figure 3). The single patient who failed stem cell harvest
had recently undergone pelvic irradiation for a symptomatic
lytic bone lesion and had a prior history of breast cancer
treated with adjuvant chemoradiation.
The remaining 37 patients underwent high-dose melphalan with auto-SCT. Neutrophil engraftment (ANC X500/
mm3) was rapid post transplant occurring at a median of 11
days (range 9–14). Median time to platelet engraftment
(platelets X20 000/m3 sustained for 7 days without
transfusion) also occurred at 11 days (range
9–31; Figure 4).
Response assessment 90–120 days after HDCT showed
CR þ VGPR in 17 patients (43%) and PR in 14 patients
(35%). In addition, seven patients (18%) had stable disease
and two patients (5%) showed disease progression at this
time (Table 3).
deceased because of progressive disease. In an intention-totreat analysis, the Kaplan–Meier estimate of the median
EFS was 770 days (range 191–1446) from the start of any
induction chemotherapy as the baseline and 607 days
(range 5–1116) from the start of pre-transplant bortezomib
with a 3-year Kaplan–Meier estimate of EFS of 38.2 and
32.3%, respectively (Figure 5). Median OS has not been
reached with a 3-year Kaplan–Meier estimate of OS of
63.1% from the start of induction therapy and 62.2% from
the start of bortezomib. No differences in either EFS or OS
were observed in patients who achieved at least a VGPR
versus those who did not with their autologous transplant
(EFS hazard ratio 0.4874, 95% CI: 0.3125–1.741, P ¼ 0.67;
OS hazard ratio 0.8602, 95% CI: 0.26–2.8, P ¼ 0.80).
Serum M-protein (g/100 ml)
Peripheral blood subset analysis
PBL subsets analysis at baseline and after two cycles of pretransplant bortezomib revealed a 38% decrease in the
absolute number of circulating natural killer cells (CD45 þ ,
CD3, CD56 þ , P ¼ 0.022). The CD4/CD8 ratio increased
by 26% (P ¼ 0.0006), which was secondary to a decrease in
the absolute number of cytotoxic T cells (CD45 þ , CD3,
CD4, CD8 þ , P ¼ 0.055; Table 2). Changes in T-cell
subsets occurred without any significant change in total
lymphocyte counts.
Figure 3 M-protein response to pre-transplant therapy. Serum monoclonal protein levels (n ¼ 31) measured at baseline before induction
chemotherapy, before pre-transplant bortezomib and after two cycles of
pre-transplant bortezomib.
Lymphocyte subsets at baseline and after two cycles of bortezomib
CD45+ and CD2+
CD45+ and CD3+
CD3+, CD4+ and CD8
CD3+, CD4 and CD8+
CD3 and CD19+
CD3 and CD20+
CD3 and CD56+
CD4/CD8 ratio
Bone Marrow Transplantation
Pre-bortezomib (/mm3)
Post-bortezomib (/mm3)
Absolute difference (/mm3)
P-value
1446
1273
842
412
90
87
206
2.53
1259
1160
802
337
94
95
148
3.19
187
113
40
75
4
8
58
0.66
0.085
0.28
0.54
0.055
0.86
0.78
0.022
0.0006
Bortezomib pre- and post transplant
GL Uy et al
100
1.5x107
80
% Engraftment
CD34+/kg body weight
797
1.8x107
1.3x107
1.0x107
7.5x106
5.0x106
2.5x106
60
40
Neutrophill
Platelet
20
0
0
1st
2nd
3rd
4th
Apheresis collection
0
5th
5
10
15
20
25
30
Days post transplant
Figure 4 Stem cell mobilization and engraftment. (a) Number of G-CSF mobilized CD34 þ stem cells per kg body weight harvested in each large volume
(20 l/day) apheresis session (n ¼ 38). (b) Neutrophil (ANC X500/mm3) and platelet engraftment (platelets X20 000/mm3 sustained for 7 days without
transfusion) post stem cell infusion after high-dose melphalan (n ¼ 37).
Table 3
Response evaluation (n ¼ 40)
Post transplant (+90 to 120 days)
n (%)
CR+VGPR
PR
CR+VGPR+PR
SD
PD
17
14
31
7
2
End of the treatment
n (%)
(43)
(35)
(78)
(18)
(5)
17
12
29
5
6
Best overall response
n (%)
(43)
(30)
(73)
(13)
(15)
20
13
33
5
2
(50)
(33)
(83)
(13)
(5)
Abbreviations: PD ¼ progressive disease; PR ¼ partial remission; SD ¼ stable disease; VGPR ¼ very good partial remission.
100
% Overall survival
100
% EFS
75
50
25
75
50
25
0
0
0
500
1000
Days
1500
2000
0
500
1000
Days
1500
2000
(a) EFS and (b) overall survival (OS) for patients (n ¼ 40) measured from either the start of induction chemotherapy (solid) or from the start of
pre-transplant bortezomib (dashed).
Figure 5
Table 4
Adverse events UXgrade 2
Grade 2 (n)
CNS ischemia
Diarrhea
Eosinophilia
Fracture
Gastrointestinal obstruction
Hernia
Nausea
Neuropathy
Neutropenia
Pain (general)
Rash
Vomiting
Grade 3 (n)
Grade 4 (n)
1
1
1
2
1
1
2
7
1
3
2
2
3
bortezomib administration. No other grades 3–4 toxicities
were observed during bortezomib administration.
In addition to neuropathy, herpes virus infections were
common, with 15 (38%) patients developing reactivation of
varicella zoster at a median of 206 days from the start of the
study (range 25–375 days). Thirteen cases (33%) occurred
post transplant with nine (23%) occurring during bortezomib consolidation.
2
neuropathy, bortezomib was discontinued in two patients
and the dose reduced in an additional two patients. One
patient developed cerebrovascular ischemia during G-CSF
mobilization, which was judged to be unrelated to
Discussion
This is the first study to report on the feasibility and
efficacy of an approach in which bortezomib is administered sequentially pre-transplant and as maintenance post
transplant. This study was initiated before the commercial
availability of bortezomib. Because of local referral
patterns, we allowed the enrollment of patients who had
received induction therapy with community oncologists
Bone Marrow Transplantation
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GL Uy et al
798
before referral to our transplant center. The modest effect
of bortezomib on paraprotein levels when given subsequent
to pre-transplant may reflect the short (2-cycle) exposure
and possibly the proliferation characteristics of the cell
residual malignant cells.
The effect on the subsequent collection of autologous
stem cells remains an important consideration in the choice
of initial therapy in multiple myeloma. Our study complements reports of successful stem cell collection after
treatment with bortezomib using chemotherapy þ G-CSF
and G-CSF alone for mobilization of stem cells.9 In
contrast, recent studies indicate that lenalidomide adversely
affects stem cell mobilization. Kumar et al.14 reported
decreased CD34 yields and an increase in number of
apheresis collections in patients treated with lenalidomide
compared with those receiving thalidomide and dexamethasone or VAD regimens. Furthermore, an inverse correlation was seen between stem cell yield and duration of
lenalidomide therapy. Mazumder et al.15 confirmed these
results of lower stem cell yield with 12 of 28 patients failing
to collect sufficient stem cells (o2 106 CD34 þ /kg) for
even a single transplant. In addition, three patients failed to
mobilize with a subsequent AMD3100 þ G-CSF compassionate use of protocol. Although chemotherapy with
G-CSF regimens may be considered in patients receiving
lenalidomide upfront, chemomobilization is associated with
increased toxicity because of the regimen itself and with
higher resource utilization because of the difficulties in
optimal timing of stem cell harvest.
In earlier studies of HDCT, patients achieving CR post
transplant had longer EFS and DFS compared with those
who did not. Currently, therefore, there is interest in using
immunomodulatory drugs and bortezomib in combination
regimens to maximize depth of response post transplant.
Recent randomized studies have shown that the response
rates achieved after autologous transplant were similar
when either thalidomide and dexamethasone or VAD were
used as pre-transplant induction therapy.16 In contrast,
combination therapy with bortezomib and dexamethasone
had higher CR þ VGPR rates post transplant when
compared with VAD chemotherapy (62 versus 42%,
Po0.0001).17 Similarly, combination therapy with bortezomib, thalidomide and dexamethasone produced superior
CR þ VGPR rates post transplant when compared with
thalidomide and dexamethasone alone (77 versus 54%).18
Unfortunately, follow-up as reported is short, and currently the impact of these different induction regimens on
EFS and OS survival is not known. In our series, we report
that 43% had a CR þ VGPR post transplant and we
provide a median of 27 months F/U data on a bortezomibcontaining pre-transplant regimen.
A number of agents have been tested in the post
transplant setting to improve both the depth and durations
of responses. IFN-a with or without steroids has been
studied extensively both with standard and HDCT with
variable benefit for PFS but no improvement in OS.19–22
Alternative day dosing prednisone improved OS after
conventional therapy but is not well tolerated or accepted
by patients or physicians.23 Among newer agents, Attal
et al.24 showed that thalidomide maintenance for 1 year
increases both 3-year EFS (37–52%, Po0.009) and OS
Bone Marrow Transplantation
(87 versus 75% at 4 years, P ¼ 0.04). However, this
advantage was limited to individuals who attained less
than VGPR after HDCT. In addition, no benefit was seen
in patients with a del13 karyotype. Here, we show the
feasibility of post transplant bortezomib therapy in multiple myeloma. We chose a once-weekly regimen of administration in the post transplant period for convenience. The
schedule of weekly bortezomib 1.3 g/m2 is well tolerated
without adverse hematologic effects or a significant
worsening of peripheral neuropathy. By using this dose of
bortezomib, we did not see any appreciable drop in
paraprotein levels. Other investigators have reported on
the clinical activity of bortezomib 1.6 g/m2 in myeloma.25,26
However, our trial was designed before data on the higher
once-weekly dose regimen became available.
It is difficult to make definitive conclusions on the longterm benefit of bortezomib administered post transplant.
The EFS of 25.7 months observed in this study with
bortezomib maintenance is similar to previously published
studies of a single autologous transplantation.1,2,27 The fact
that thalidomide maintenance did not improve survival in
patients who had already achieved a VGPR with HDCT
has been suggested by some to mean that thalidomide
acts as consolidation therapy rather than maintenance
therapy in the post transplant setting.24 It is plausible that
schedules of bortezomib, which are more successful in
increasing the depth of response post transplant, may lead
to better long-term outcomes. Such studies are currently
ongoing.
Although the anti-myeloma effect of bortezomib is not
fully understood, the anti-proteasomal activity of bortezomib inhibits nuclear factor-kB and the downstream
expression of genes critical for cell survival.28 Nuclear
factor-kB is implicated in the regulation of many genes that
code for mediators of the immune and inflammatory
response. Bortezomib has been shown to potently inhibit
in vitro MLR and promote apoptosis of alloreactive T cells.
In a murine model, this led to inhibition of GVHD with
retention of graft versus tumor effects.29 However, the same
authors showed that the delayed administration of bortezomib resulted in increased GVHD-dependent gastrointestinal toxicity.30 Bortezomib may be explored as an agent
to modulate graft-versus-host and graft-versus-malignancy
effects.
In this study, the analysis of peripheral lymphocyte
subsets suggests that bortezomib is selectively toxic to
normal cytotoxic CD8 þ T cells and natural killer cells.
Bortezomib has shown clinical activity against a number of
lymphoid malignancies including mantle cell lymphoma,
follicular and peripheral T-cell non-Hodgkin’s lymphoma.31,32 In addition, bortezomib has been shown to reduce
circulating CD3 þ T cells when administered post-allogeneic transplant in patients with myeloma.33 As cellmediated immune responses are important in controlling
primary VZV infection and maintaining viral latency, the
effect of bortezomib on normal CD8 þ and CD56 þ
lymphocyte subsets may explain the high rate of viral
reactivation.34 High rates of VZV reactivation have been
noted in both phase II and phase III studies of bortezomib.
In the Assessment of Proteasome Inhibition for Extending
Remissions study, VZV reactivation was seen in 13% in the
Bortezomib pre- and post transplant
GL Uy et al
799
bortezomib arm compared with 5% in the dexamethasone
arm.35 Our data suggest that patients post transplant may
be at higher risk for developing reactivation. This
information may have a particular impact in ongoing
studies that incorporate bortezomib in the post transplant
setting both in multiple myeloma and in diseases such as
mantle cell lymphoma. For these patients, more prolonged
routine viral prophylaxis with acyclovir or valacyclovir
may result in lower rates of virus reactivation.
In conclusion, our study adds to the growing literature
that, unlike lenalidomide, pre-transplant induction therapy
with bortezomib has no adverse impact on the mobilization
of autologous stem cells. With short-duration acyclovir
prophylaxis, bortezomib administration in the peri-transplant period resulted in high rates of reactivation of herpes
zoster. Interpretation of the role of bortezomib maintenance in myeloma based on this single study is limited
because of the relatively small sample size and relatively
short duration of maintenance therapy. Larger prospective
randomized studies of post transplant bortezomib are
required and are currently ongoing.
Acknowledgements
Research funding and bortezomib for the clinical trial were
provided by Millennium Pharmaceuticals.
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