Written in Blood
effective bridge to AHCT that replaced the
need for cytotoxic chemotherapy for the
majority of patients,” the authors wrote.
At six months, the median duration
of response and median progression-free
survival (secondary endpoints) were not
reached.
Most patients (n=60; 98%) experienced
treatment-related adverse events (AEs) pri-
or to AHCT or alternative salvage therapy.
The most common AEs were nausea (49%),
infusion-related reactions (IRRs; 44%),
and fatigue (41%). Nineteen patients (31%)
reported grade ≥3 AEs, the most common
of which were anemia, febrile neutropenia,
hypophosphatemia, and neutropenia (n=2
[3%] for each). Twelve patients (20%) re-
ported peripheral neuropathy. Six patients
(10%) experienced serious AEs, including
pneumonitis, pneumonia, pyrexia, malaise,
nausea, and rash.
Because of the high rate of IRRs (which
occurred more frequently and severely
with the combination than with indi-
vidual agents alone), the study protocol
was amended to include mandatory
premedication with low-dose corticoste-
roids, antihistamine, and hydrocortisone
at cycles two through four. “Nonetheless,
the rate of [IRRs at] cycle two was largely
unchanged before and after premedication,”
the authors wrote, “while the rate of IRRs
during cycles three through four remained
low, irrespective of premedication.”
During study follow-up, 16 patients
discontinued one of the study drugs: seven
(11%) discontinued brentuximab vedotin
and nine (15%) discontinued nivolumab due
to asymptomatic laboratory abnormalities
(n=8), pneumonia (n=2), thrombosis (n=2),
chills (n=1), pneumonitis (n=1), syncope
(n=1), and urticaria (n=1). IRRs did not lead
to treatment discontinuation, the researchers
noted, but led to brentuximab vedotin dose
T:1
S:14
EXPLORE THE COVERAGE
OF KOVALTRY ®
Cross-over PK study: KOVALTRY ® and Advate ®2,3
Study summary
The PK profi les of KOVALTRY ® and Advate ® were compared in a single-dose, open-label,
randomized, cross-over study of 18 PTPs
(aged 18–65 years) with severe hemophilia A
KOVALTRY ®
KOVALTRY ®
(n=9)
(n=9)
Patients were randomized to a single infusion of
either drug (50 IU/kg, n=9 for each arm), then after
Advate ®
Advate ®
≥3-day
(n=9)
(n=9)
a ≥3-day washout period they were crossed over to
washout period
a single infusion of the other treatment
Plasma samples were collected predose and postdose (at 0.25, 0.5, 1, 3, 6, 8, 24, 30, and
48 hours)
PK results
Cross-over PK study results (geometric mean [%CV]) following single-dose
administration (50 IU/kg) of KOVALTRY ® and Advate ® in 18 patients
Chromogenic assay KOVALTRY ® Advate ® P value
AUC 0-inf
(IU•h/dL)
C max
(IU/dL)
t 1/2
(h)
CL
(dL/h/kg) 2440
(28.5) 1650
(31.0) <0.0001
151
(19.9) 153
(17.1) 0.32
13.9
(25.1) 12.0
(23.3) <0.0001
0.021
(28.5) 0.030
(31.0) <0.0001
AUC 0-inf =area under the curve from time 0 to infinity.
CL=clearance.
CV=coefficient of variation.
PTP=previously treated patient.
SELECTED IMPORTANT SAFETY INFORMATION
KOVALTRY ® may contain trace amounts of mouse and hamster proteins. Patients treated
with this product may develop hypersensitivity to these non-human mammalian proteins.
Neutralizing antibody (inhibitor) formation can occur following administration of KOVALTRY ® .
Previously untreated patients (PUPs) are at greatest risk for inhibitor development with all
Factor VIII products. Carefully monitor patients for the development of Factor VIII inhibitors,
using appropriate clinical observations and laboratory tests. If expected plasma Factor VIII
activity levels are not attained or if bleeding is not controlled as expected with administered dose,
suspect the presence of an inhibitor.
FS:6.75”
.5”Gutter