CLINICAL NEWS
Patients were excluded from
the study if they had congestive heart failure, symptomatic
ischemia, conduction system
abnormalities uncontrolled by
conventional intervention, myocardial infarction in the previous six months or uncontrolled
hypertension, or significant
neuropathy.
The study’s primary endpoint was identifying the MTD.
Secondary endpoints included
the preliminary efficacy of CPD
in terms of overall response
rate (ORR), complete response
rate, very good partial response
(VGPR) rate, partial response
rate (PRR), minimal response
rate (MRR), time to progression,
progression-free survival (PFS),
and overall survival (OS).
Per treatment protocol, all
patients received:
• Carfilzomib intravenously over
30 minutes on days 1, 2, 8, 9,
15, and 16 every 28 days for the
first six cycles, with a starting
dose of 20/27 mg/m2
• Pomalidomide orally once
daily on days 1 through 21
every 28 days, with a 4 mg
initial starting dose
• Dexamethasone
40 mg delivered orally or
intravenously on a weekly basis
on days 1, 8, 15, and 22 of 28day cycles
After the first four cycles, it was
recommended that the dexamethasone dose be reduced to 20 mg. After six cycles of treatment, patients
could continue on maintenance
therapy as long as, in the eyes of
the investigator, they were deriving
clinical benefit from the drugs.
All patients were evaluated
for hematologic and non-hematologic dose-limiting toxicities.
Of the 32 patients included in
the study, 28 patients had an
adverse event related to the
study treatment or an infection:
63 percent of patients (n=20)
had a grade 3 event, 31 percent
(n=10) had a grade 4 event, and
6 percent of patients (n=2) had
fatal events of pneumonia and
pulmonary embolism (TABLE
1). Five patients (16%) received
platelets transfusions, and 19
patients (59%) required at least
one transfusion of red blood
cells (median = 1; range 0-13).
“Treatment-emergent peripheral
neuropathy was uncommon,
with six patients experiencing
grade 1 peripheral neuropathy
and one patient experiencing
grade 2 peripheral neuropathy,”
the authors noted.
Additional reported hematologic and non-hematologic toxicities can be found in TABLE 1.
Eight patients had dose reductions during therapy, and seven
patients discontinued treatment
due to adverse events. Patients
received a median of seven treatment cycles.
In terms of the secondary endpoints, the ORR was 50 percent
among the study patients, with:
• 16% of patients achieving
VGPR
• 34% achieving PRR
• 16% achieving MRR
• 25% with stable disease
An analysis of response rate
according to MM subtype is
provided in TABLE 2. After a median follow-up of 26.3
months (range = 1-37
months), the median
TABLE 1. Adverse Events, by Maximum Grade Reported
PFS was 7.2 months
Grade
(95% CI 3-9) and
Total (N=32)
median OS was 20.6
1
2
3
4
5
months (95% CI 11.9Hematologic adverse events, n
28.7), with a 12-month
Anemia
0
4
5
1
0
10
OS rate of 67 percent.
Thrombocytopenia
0
3
4
3
0
10
“[CPD] is quickly
becoming
a standardNeutropenia
0
4
10
4
0
18
of-care
option
for
Febrile neutropenia
0
0
2
0
0
2
patients with lenalidNon-hematologic adverse events, n
omide-refractory myDiarrhea
4
1
0
0
0
5
eloma, with response
Constipation
6
0
0
0
0
6
rates and survival
superior to either drug
Nausea
1
1
1
0
0
3
alone,” Dr. Shah said,
Emesis
0
1
1
0
0
2
however there were
Fatigue
5
9
1
0
0
15
limitations with this
Dyspnea
8
2
1
0
0
11
study. For instance,
grade 3 rashes ocRash
4
0
1
0
0
5
curred, which limited
Neuropathy/paresthesia
6
1
0
0
0
7
the researchers’ ability
Congestive heart failure
0
0
1
0
0
1
to escalate the dose,
Muscle spasms
4
2
0
0
0
6
and, as a result, the
MTD may have been
Transient ischemic attack
0
0
1
0
0
1
underestimated. AddiPulmonary emboli
0
0
1
0
1
2
tionally, the number of
Deep vein thrombosis
0
1
0
0
0
1
patients included in the
Creatinine elevation
5
4
1
2
0
12
study was limited. The
Pneumonia
0
0
3
0
1
4
researchers suggested
that in future studies, a
subsequent dose escaTABLE 2. Response Rate in All Intent-to-Treat Patients and by Cytogenetic
lation is conducted in
less heavily pretreated
Abnormalities
patients to reevaluate
All evaluable
Hyperdiploid
Response Rate
Del(13) (n=9)
Del(17p) (n=5)
the MTD of this treatpatients (n=32)
(n=10)
ment combination. ●
Overall response rate
16 (50%)
5 (50%)
1 (11%)
4 (80%)
Very good partial response
6 (16%)
1 (10%)
1 (11%)
1 (20%)
Partial response
11 (34%)
4 (40%)
0
3 (60%)
Minimal response
5 (16%)
3 (30%)
3 (33%)
0
Stable disease
8 (25%)
2 (20%)
5 (56%)
1 (20%)
Progressive disease
3 (9%)
0
0
0
ASHClinicalNews.org
REFERENCE
Shah JJ, Stadtmauer EA, Abonour R,
et al. Carfilzomib, pomalidomide, and
dexamethasone (CPD) in patients with
relapsed and/or refractory multiple
myeloma. Blood. 2015 September 4.
[Epub ahead of print]
ASH Clinical News
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