Written in Blood
Panobinostat, Dexamethasone,
Bortezomib Combo Effective in
Heavily Pretreated MM Patients
The addition of panobinostat to
bortezomib and dexamethasone
improved progression-free survival (PFS) and duration of response
compared with bortezomib and
dexamethasone alone in patients
with relapsed/refractory multiple
myeloma (MM) who had been
treated with two or more prior
regimens (including bortezomib
and an immunomodulatory drug
[IMiD]) – providing guidance as to
which patients would benefit more
from the novel drug, according to
the results of a subgroup analysis of
the PANORAMA 1 trial by Paul G.
Richardson, MD, from the DanaFarber Cancer Institute in Boston,
Massachusetts, and colleagues.
Panobinostat, a histone deacetylase inhibitor, was approved by the
U.S. Food and Drug Administration
in February 2015 in combination
with bortezomib and dexamethasone for the treatment of multiple
myeloma in patients who had received two or more prior therapies.
“The results from PANORAMA
1 clearly demonstrated that panobinostat increases the median PFS of
patients with relapsed or relapsed/
refractory MM when added to
bortezomib and dexamethasone,” Dr.
Richardson and colleagues wrote.
“However, patients who progress
following treatment with bortezomib
and IMiDs have a poor prognosis.”
The goal of this analysis was to
determine which patients would derive the most benefit from the pano-
binostat combination: those with
prior IMiD treatment (n=485), prior
bortezomib and IMiD treatment
(n=193), or patients receiving two
or more prior regimens (including
bortezomib and an IMiD; n=147).
“As expected, patients in the
groups with prior bortezomib plus
an IMiD and ≥2 prior regimens
including bortezomib and an IMiD
were more heavily pretreated and
demonstrated a longer time since
diagnosis than did the patients in
the prior IMiD group,” the authors
reported.
As seen in TABLE 1, median PFS
for the panobinostat combination
was longer than that for patients receiving bortezomib/dexamethasone
alo ne across all subgroups, but the
increase was greatest among patients
who had received ≥2 prior regimens.
Secondary endpoints of efficacy
(including complete remission [CR]
rate, time to response, duration of
response, and time to progression)
were also consistently improved
among pre-treated, panobinostattreated patients. “The rate of
high-quality responses more than
doubled [in these patients] across all
subgroups, with a notable increase
among patients with ≥2 prior regimens (21.9% vs. 8.1%; p=0.023),” Dr.
Richardson and colleagues wrote.
Patients treated with panobinostat also had a longer duration of
response than those treated with placebo, in combination with bortezomib and dexamethasone – particu-
larly for patients who received prior
IMiD + bortezomib: 11.99 months
(95% CI 9.69-13.90) versus 8.31
months (95% CI 6.14-12.32). These
heavily-pretreated patients also
demonstrated a greater improvement
in treatment-free interval (TFI) with
panobinostat: 4.7 months versus 1.9
months.
Common grade 3 or 4 adverse
events (AEs) and laboratory abnormalities in patients who received
panobinostat across the subgroups
included thrombocytopenia, lymphopenia, neutropenia, diarrhea, and
asthenia/fatigue (TABLE 2). Overall,
the authors wrote, “the safety profile
of the panobinostat combination was
similar among the prior treatment
subgroups.” However, the number
of on-treatment deaths was higher
among panobinostat-treated patients
who had been received prior IMiDs
than among patients in the placebo
group (17 vs. 10).
“As treatment options for
relapsed MM increase with the
development of novel therapies and
treatment combinations, it is critical
to identify patient populations that
derive the greatest benefit to aid
physicians in treatment decisions,”
Dr. Richardson and co-authors
concluded. “Investigation of other
novel panobinostat combinations
continues, including combinations
with carfilzomib, ixazomib, and lenalidomide, in order to identify new
treatment alternatives for patients
with limited options and provide additional insight on the safety profile
of this novel agent.” ●
REFERENCE
Richardson PG, Hungria VTM, Yoo SS, et al. Panobinostat
plus bortezomib and dexamethasone in relapsed/relapsed
and refractory myeloma: outcomes by prior treatment.
Blood. 2015 December 2. [Epub ahead of print]
The Fresher, the
Better? How Does
Age of Transfused Red
Blood Cells Affect
Patient Outcomes?
A meta-analysis of randomized clinical
trials examining the effect of the age of
transfused red blood cells (RBCs) on
patient outcomes revealed that, when
it comes to RBC transfusion, age is just
a number. Transfusion with blood that
had been stored for a longer period of
time was not associated with an increase
in death or adverse events (AEs) – but,
paradoxically, was associated with a
lower risk of infection – over “fresher”
blood, according to the report by Paul
E. Alexander, MHSc, MSc, from the
Department of Clinical Epidemiology
and Biostatistics at McMaster University
in Hamilton, Ontario.
“Results suggest
that, if anything,
fresher red blood
cells might lead
to an increase
rather than a
decrease in [hospital-acquired]
infections.”
—PAUL E. ALEXANDER, MHSc, MSc
TABLE 1.
Median Progression-Free Survival Among Treatment Groups
Prior treatment
IMiD
Events
Median PFS, months (95% CI)
PAN + BTZ
+ DEX
Placebo + BTZ
+ DEX
PAN + BTZ
+ DEX
Placebo + BTZ
+ DEX
Hazard ratio
(95% CI)
132/245
171/240
12.3 (10.3-13.8)
7.4 (6.0-7.9)
0.54 (0.43-0.68)
BTZ + IMiD
57/94
72/99
10.6 (7.3-13.8)
5.8 (4.4-7.1)
0.52 (0.36-0.76)
≥2 Regimens
(including
bortezomib +
IMiD)
44/73
54/74
12.5 (7.3-14.0)
4.7 (3.7-6.1)
0.47 (0.31-0.72)
PAN=panobinostat; BTZ=bortezomib; DEX=dexamethasone
TABLE 2.
Most Common Grade 3 or 4 Adverse Events
Prior IMiD
Prior BTZ + IMiD
≥2 Prior Regimens,
including BTZ + IMiD
Thrombocytopenia
162 (27%)
63 (69%)
49 (68%)
Lymphopenia
130 (54%)
97 (41%)
35 (49%)
Neutropenia
89 (37%)
33 (36%)
29 (40%)
Diarrhea
63 (26%)
28 (30%)
55 (76%)
Asthenia/fatigue
61 (25%)
23 (25%)
19 (26%)
30
ASH Clinical News
“Red blood cell transfusion is one of
the most common medical treatments,
with approximately 85 million red blood
cell units transfused annually worldwide,” Dr. Alexander and co-authors
wrote. “The impact of even a small risk
could have significant patient impact
globally.”
Longer storage of RBCs has been
shown to lead to morphologic changes
that could have a deleterious impact on
oxygen delivery, including changes to the
cell shape and membrane, an increase in
adhesiveness, and a decline in flexibility
that can hamper blood flow hemodynamics. The storage medium, as well,
could generate superoxides and inflammatory mediators that could results in
oxidative damage.
However, studies examining whether
any benefit exists for transfusing fresher
January 2016