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PAPER SPOTLIGHT
Off-Label Rituximab Proves
Its Mettle in Adult ITP
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For adult patients
with persistent or
chronic immune
thrombocytopenia (ITP),
off-label treatment
with rituximab proved
a safe and effective
management option,
according to results of a
prospective, multicenter
registry study published
recently in Blood. ITP is
an autoimmune disease
in which a patient’s
immune system destroys
platelets, leaving the
person with too few
platelets in the blood.
Rituximab, an antiCD20 chimeric monoclonal
antibody, attaches to the
B-cells that help cause
the platelet destruction
seen in ITP, ultimately
destroying them. It has
been an off-label secondor third-line ITP treatment
for more than a decade.
Despite this, the safety
profile of rituximab in
ITP clinical practice had
not been established.
Little was known about
the predictive factors for
ASHClinicalNews.org
sustained response, and
the optimal therapeutic
regimen for the drug in
ITP treatment had not
been defined, the authors,
led by Mehdi Khellaf, MD,
explained.
In the current study,
Dr. Khellaf, of the Centre
Hospitalier Universitaire
Henri-Mondor in Creteil,
France, and colleagues
assessed response and
predictive factors of
sustained response in 248
adults who had previously
received corticosteroids
or intravenous immunoglobulin (IVIg) as first-line
treatment for ITP.
Two rituximab protocols
were used:
• A “lymphoma-like”
regimen of four weekly
doses of 375 mg/m2 in
173 patients
• A “rheumatoid arthritis
(RA)-like” regimen of
fixed 1-g doses on days
1 and 15 in 72 patients.
Three patients received a
regimen of a single infusion.
At a median follow-up
of two years, there was
a cumulative incidence
of 2.3 infections per 100
patient years, Dr. Khellaf
et al reported. Three
patients died of infection
after rituximab infusions,
the authors noted, but
the role of rituximab
in these deaths was
“questionable.”
In total, 152 patients
(61%) showed an
overall initial response
– defined as a platelet
count ≥30x109/L and
at least twice their
baseline value. Ninetysix patients (39% of the
total population) showed
a lasting response at 24
months, including 76 with
complete response, the
researchers reported.
Dr. Khellaf and
colleagues noted
that “on multivariate
analysis, the probability
of sustained response
at one year was
significantly associated
with ITP duration <1
year (p=0.02) and
previous transient
complete response to
corticosteroids (p=0.05).”
The results indicate
a positive future for
rituximab in ITP treatment, co-author Bertrand
Godeau, MD, also from
the Creteil institution,
told ASH Clinical News.
Comparing regimens
with respect to safety,
Dr. Godeau commented,
“There is really no lower
adverse event incidence
of the RA-like regimen,
meaning the tolerance
between the two
regimens was similar.”
First-line treatment of
ITP includes observation,
corticosteroid therapy,
IVIg, or anti-D immunoglobulin (anti-D). This
is followed by surgical
removal of the spleen
if first-line treatment
is unsuccessful. “We
consider that rituximab
is a second- or third-line
treatment for ITP before
splenectomy,” Dr. Godeau
said. “Even if the longterm response is modest,
our study confirms that,
two years after rituximab
infusions, about 40 percent of the patients have
a response.”
“The findings of this
large prospective registry of patients with ITP
treated with rituximab in
‘real life’ show that the
safety profile is acceptable and confirm that the
treatment leads to an
overall response rate of
39 percent at two years,”
Dr. Khellaf and co-authors
concluded. “With its benefit/risk ratio, off-label
rituximab may remain a
valid option, particularly
for young patients with
persistent ITP and a previous transient complete response to corticosteroids
because this subgroup
has a high probability of
sustained response.”
Reference
• Khellaf M, Charles-Nelson A, Fain O,
et al. Safety and efficacy of rituximab
in adult immune thrombocytopenia:
results from a prospective registry
including 248 patients. Blood. 2014
October 7. [Epub ahead of print]
ASH Clinical News
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