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initiated, non-randomized, multicenter,
open-label study to assess the optimal dose of
REP and evaluate the safety of this combination in 82 patients enrolled at 10 hospitals in
the Netherlands between August 2001 and
November 2014.
Patients with MM were eligible if they
were refractory to lenalidomide (defined
as progressive disease during therapy, no
response to prior lenalidomide-containing
therapy, or within 60 days of
discontinuation from lenalidomidecontaining regimens) following at
least one prior therapy.
The median patient age was
66 years (range = 41-82 years),
and the median number of prior
therapies was three (range =
1-10 treatments). Most patients
(n=66; 80%) had progressive
disease during lenalidomide-based
therapy, while 14 percent (n=11)
had progression within 60 days of
stopping lenalidomide-containing
therapy and 6 percent (n=5) had no
response to lenalidomide-containing
therapy. In addition, 66 percent of
patients (n=54) were refractory to
bortezomib.
Lenalidomide was administered
on days one through 21 of a 28-day
cycle, and cyclophosphamide and
prednisone given continuously until
disease progression.
According to results from the
phase I, dose-finding trial, in which
21 patients were treated at five
different dose levels, the maximumtolerated dose (MTD) of REP was
determined to be lenalidomide 25
mg and cyclophosphamide 50 mg/
day plus prednisone 20 mg/day.
In the phase II expansion safety
and efficacy study, 61 new patients
were enrolled, as well as seven
patients who had been treated with the MTD
in phase I. Patients received a median of nine
REP cycles (range = 1-30 cycles).
The most common hematologic adverse
event (AE) was grade 3 (n=13; 19%) and
grade 4 (n=2; 3%) neutropenia. Grade 3
anemia occurred in 4 percent of patients,
while grade 3 (n=10; 15%) and grade 4 (n=5;
7%) thrombocytopenia also occurred. The
most common non-hematologic AEs included
infections (grade 3 = 18%), mostly upper and
lower respiratory tract infections, as well as
pneumonia with septic shock (n=2; 3%), and
cardiac disorders (n=5). No second primary
malignancies were observed.
Treatment-related AEs resulted in at least
one level of dose reduction of lenalidomide
in 11 patients (16%), but no dose reductions
for cyclophosphamide or prednisone were
required. Eight patients (12%) discontinued
TWICE-WEEKLY
+ SIMPLE,*
=
DOSING SCHEDULE
conversations THEIR WAY
PROVEN
PROPHYLAXIS
Proven results with ADYNOVATE
+ Zero median ABR for joint or spontaneous bleeding
episodes while on prophylaxis†1
+ 98% of patients (n=120) remained on their starting dose and did
not need a dose adjustment. Only 2 people increased their dose
to 60 IU/kg during prophylaxis due to bleeding in target joints1
*ADYNOVATE allows patients to infuse on the same 2 days every week.1
†
Joint: 0.0 (Q1: 0.0; Q3: 2.0) median vs on-demand 38.1 (Q1: 24.5; Q3: 44.6); 2.9 (SD 8.0)
mean vs on-demand 34.7 (SD 15.1). Spontaneous: 0.0 (Q1: 0.0; Q3: 2.2) median vs
on-demand 21.6 (Q1: 11.2; Q3: 33.2); 2.9 (SD 7.1) mean vs on-demand 26.0 (SD 19.6).1,2
The safety, efficacy, and pharmacokinetics (PK) of ADYNOVATE were evaluated in a
multicenter, open-label, prospective, nonrandomized, 2-arm clinical study (N=137) that
compared the efficacy of a twice-weekly prophylactic treatment regimen to on-demand
treatment and determined hemostatic efficacy in the treatment of bleeding episodes.1
For patients 12 years and older with hemophilia A
For more information,
visit www.ADYNOVATEPRO.com
ABR=annualized bleeding rate.
“Patients who
have doublerefractory MM
have a very
poor outcome,
but REP induces a high
response rate
and relatively
long PFS.”
–NIELS VAN DE DONK, MD, PhD
ADYNOVATE [Antihemophilic Factor
(Recombinant), PEGylated] Important Information
Indication
ADYNOVATE, Antihemophilic Factor (Recombinant), PEGylated,
is a human antihemophilic factor indicated in adolescent
and adult patients (12 years and older) with hemophilia A
(congenital factor VIII deficiency) for:
• On-demand treatment and control of bleeding episodes
• Routine prophylaxis to reduce the frequency of
bleeding episodes
ADYNOVATE is not indicated for the treatment of
von Willebrand disease.
DETAILED IMPORTANT RISK INFORMATION
CONTRAINDICATIONS
ADYNOVATE is contraindicated in patients who have had prior
anaphylactic reaction to ADYNOVATE, to the parent molecule
(ADVATE [Antihemophilic Factor (Recombinant)]), mouse
or hamster protein, or excipients of ADYNOVATE (e.g. Tris,
mannitol, trehalose, glutathione, and/or polysorbate 80).
WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions are possible with ADYNOVATE.
Allergic-type hypersensitivity reactions, including
BAXALTA, ADVATE and ADYNOVATE are trademarks or registered trademarks of Baxalta Incorporated, a wholly owned, indirect subsidiary
of Shire plc. SHIRE and the Shire Logo are trademarks or registered trademarks of Shire Pharmaceutical Holdings Ireland Limited
or its affiliates. USBS/MG159/16-0048
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anaphylaxis, have been reported with other recombinant
antihemophilic factor VIII products, including the parent
molecule, ADVATE. Early signs of hypersensitivity
reactions that can progress to anaphylaxis may include
angioedema, chest tightness, dyspnea, wheezing,
urticaria, and pruritus. Immediately discontinue
administration and initiate appropriate treatment if
hypersensitivity reactions occur.
Neutralizing Antibodies
Formation of neutralizing antibodies (inhibitors) to factor VIII
can occur following administration of ADYNOVATE. Monitor
patients regularly for the development of factor VIII inhibitors by
appropriate clinical observations and laboratory tests. Perform
an assay that measures factor VIII inhibitor concentration if
the plasma factor VIII level fails to increase as expected, or if
bleeding is not controlled with expected dose.
ADVERSE REACTIONS
Common adverse reactions (≥1% of subjects) reported in the
clinical studies were headache and nausea.
Please see the following page for the Brief Summary
of ADYNOVATE.
References: 1. ADYNOVATE Prescribing Information.
Westlake Village, CA: Baxalta US Inc. 2. Data on file.
Baxalta Incorporated.