CLINICAL NEWS
Should ATG Be Added to Myeloablative Regimens for
Hematopoietic Cell Transplantation?
Hematopoietic cell transplantation (HCT)
is used to treat a wide range of hematologic
malignancies. One anticipated complication
is graft-versus-host disease (GVHD) – a
condition experienced by 40 to 60 percent of patients that increases their risk
for mortality and can negatively impact
quality of life. Anti-thymocyte globulin
(ATG) may ameliorate this complication, as previous studies have indicated
that pre-treatment with ATG decreases
the incidence of chronic GVHD at one
year after transplantation, without adversely affecting rates of disease relapse,
serious infection, or overall survival
(OS).
Irwin Walker, MBBS, from
McMaster University and Juravinski
Hospital and Cancer Centre in Hamilton, Ontario, Canada, and colleagues
conducted a phase III, multicenter,
open-label, randomized, controlled trial
to examine whether ATG reduces the
need for long-term immunosuppressive treatment to prevent GVHD after
transplantation.
Based on the study results, “ATG is
effective in preventing chronic GVHD,
the most serious long-term complication of HCT,” Dr. Walker told ASH
Clinical News.
The study took place between June
9, 2010, and July 8, 2013, at 10 transplant centers in Canada and one center
in Australia. Patients were eligible for
study inclusion if they had a hematologic malignancy and were receiving
either myeloablative or non-myeloablative conditioning preparative regimens
before HCT from an unrelated donor.
A total of 203 patients were randomized to receive either:
• Rabbit-derived ATG 4.5 mg/kg
administered intravenously over 3
days prior to transplant plus standard GVHD prophylaxis (n=101)
• Standard GVHD prophylaxis alone
(n=102)
Standard GVHD prophylaxis treatment included either cyclosporine or
tacrolimus with either methotrexate or
mycophenolate.
The study’s primary endpoint was
freedom from systemic immunosuppressive drugs without resumption
up to 12 months after transplantation.
Secondary endpoints included time to
neutrophil and platelet engraftment;
incidence of acute GVHD; incidence of
and time to chronic GVHD; event-free
survival; and times to non-relapse morality, all-cause mortality, and relapse of
hematologic malignancy. Patient-reported
quality-of-life measures were also analyzed.
Among the patients who were alive at
12 months, 37 percent in the ATG group
(n=37) were free from immunosuppressive
treatment, compared with 16 percent in the
no-ATG group (n=16; odds ratio [OR] =
3.02; 95% CI 1.54-5.92; p=0.0010).
When Treating Acquired Hemophilia A
PROCEED WITH CONFIDENCE
ABOUT
The first recombinant
porcine sequence factor VIII
replacement treatment1
RESPONSE
Fast-acting: 95% (19/20)
response seen at 8 h; 100%
(18/18) at 16 h; 100% (28/28)
at 24 h after initial dosing1
EFFICACY
94% (16/17) of patients
treated first-line achieved
overall treatment success1
SAFETY
Safety profile established in the
adult population in a clinical trial1
MEASURABILITY
The ability to measure factor VIII levels
helps find the right dosing balance1
The efficacy (N=28) and safety (N=29) of OBIZUR were studied
in the first interventional, prospective, clinical trial for acquired
hemophilia A (AHA) patients. Patients were treated with OBIZUR
until resolution of bleeding, or dosing was continued at the
physician’s discretion according to the clinical assessment.1
Indication
OBIZUR, Antihemophilic Factor (Recombinant), Porcine Sequence, is
a recombinant DNA derived, antihemophilic factor indicated for the
treatment of bleeding episodes in adults with acquired hemophilia A.
Limitations of Use:
• Safety and efficacy of OBIZUR has not been established
in patients with baseline anti-porcine factor VIII inhibitor
titer greater than 20 BU
• OBIZUR is not indicated for the treatment of congenital
hemophilia A or von Willebrand disease
Detailed Important Risk Information
CONTRAINDICATIONS
OBIZUR is contraindicated in patients who have had life-threatening
hypersensitivity reactions to OBIZUR or its components (including
traces of hamster proteins).
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions can occur with OBIZUR. OBIZUR
contains trace amounts of hamster proteins. Early signs
of allergic reactions, which can progress to anaphylaxis,
include angioedema, chest-tightness, dyspnea, hypotension,
wheezing, urticaria, and pruritus. Immediately discontinue
administration and initiate appropriate treatment if allergic
or anaphylactic-type reactions occur.
Visit www.OBIZUR.com
If the plasma factor VIII level fails to increase as expected, or if
bleeding is not controlled after OBIZUR administration, suspect the
presence of an anti-porcine fa