Literature Scan
Study Examines Alisertib for Relapsed/
Refractory Peripheral T-Cell Lymphoma
Alisertib, a novel oral aurora
A kinase (AAK) inhibitor, has
demonstrated antitumor activity
in patients with peripheral T-cell
lymphoma, according to results
from a phase II trial recently
published in the Journal of Clinical
Oncology. The drug also showed
no adverse safety signals, the
authors, led by Paul M. Barr, MD,
from the University of Rochester
Medical Center in Rochester, New
York, reported.
Previous early-phase studies
showed that alisertib was active
in T-cell lymphoma; the current
study further investigated the efficacy of alisertib in patients with
relapsed or refractory peripheral
T-cell non-Hodgkin lymphoma
(PTCL).
“Patients with peripheral T-cell
lymphoma tend to have very poor
outcomes,” Dr. Barr told ASH Clinical News. “Additional therapeutic
options are desperately needed
for these patients.” Because AAK
is upregulated in highly prolifera-
tive lymphomas, AAK-inhibiting
alisertib has been proposed as a
potential therapeutic target for this
patient population.
Dr. Barr and colleagues
conducted a phase II Intergroup
trial of 37 patients (median age
= 62 years; range = 22-86 years)
with PTCL. Patients were eligible
for study inclusion if they had
histologically confirmed relapsed/
refractory PTCL or transformed
mycosis fungoides (tMF).
A breakdown of the 37
participants’ histologic subtypes
included:
• PTCL not otherwise specified
(n=13)
• Angioimmunoblastic T-cell
lymphoma (n=9)
—PAUL M. BARR, MD
50
ASH Clinical News
Recent laboratory investigations
have suggested notable synergy
between alisertib and the histone
deacetylase inhibitor romidepsin,
he added, and those results are being explored further.
“Alisertib has antitumor activity in PTCL, including heavily
pretreated patients,” Dr. Barr and
colleagues concluded. “These
promising results are being further investigated in an ongoing,
international, randomized, phase
III trial comparing alisertib with
investigator’s choice in PTCL.”
REFERENCE
Barr PM, Li H, Spier C, et al. Phase II Intergroup trial
of alisertib in relapsed and refractory peripheral T-cell
lymphoma and transformed mycosis fungoides: SWOG
1108. J Clin Oncol. 2015;33:2399-2404.
• tMF (n=7)
• Adult T-cell lymphoma/
leukemia (n=4)
• Anaplastic large-cell
lymphoma (n=2)
• Extranodal natural killer/Tcell lymphoma (n=2)
“Alisertib is
active in this
population,
suggesting
aurora kinase
inhibition is
worthy of
further study
in peripheral
T-cell lymphoma.”
neutropenia (32%), anemia (30%),
thrombocytopenia (24%), febrile
neutropenia (14%), mucositis
(11%), and rash (5%).
Treatment was discontinued
in six patients (most commonly
for disease progression), and nine
patients reduced their dose due to
AEs.
“One of the main take-home
points from this [study] is that
alisertib is active in this population, suggesting aurora kinase
inhibition is worthy of further
study in PTCL,” Dr. Barr said.
“While some of the patients
had prolonged responses, most
ultimately progressed, similar to
what has been experienced with
most other treatment options.”
The patients had received a median of three prior therapies (range,
1-18 therapies), and three patients
had undergone a prior stem cell
transplant.
All patients received alisertib
50 mg twice daily for seven days
on 21-day cycles until disease progression or unacceptable toxicity.
Two patients experienced
complete responses, while seven
patients had partial responses, for
an overall response rate (ORR) of
24 percent (95% CI 12-41).
Among the PTCL subtypes,
the ORR was 33% (95% CI 16-55),
but no response was observed for
patients with tMF, Dr. Barr and coauthors noted. Of the 27 patients
who had available biopsies, zero
and six expressed AAK and aurora
B kinase (ABK), respectively, thus
ABK was more commonly overexpressed compared with AAK in
tumor specimen.
On the safety side, treatmentrelated grade 3 and 4 adverse
events (AEs) that occurred in
≥5 percent of patients included
Study of At-Home
Rivaroxaban Treatment
Supports Outpatient
Treatment for Low-Risk
DVT and PE Patients
While home treatment of venous
thromboembolism has been associated with low failure rates in
several studies, in the real-world
setting, challenges in arranging
follow-up, assuring therapy compliance, and concern about legal
ramifications should a discharged
patient develop complications
have prevented these protocols
from becoming the norm.
In a report published in
Academic Emergency Medicine,
Daren M. Beam, MD, MS, from
Indiana University School of
Medicine in Indianapolis, Indiana,
and colleagues evaluated a novel
emergency department–initiated
rivaroxaban-based protocol that
would allow early home treatment of lower-risk patients with
deep-vein thrombosis (DVT) and
pulmonary embolism (PE).
“This protocol allows the immediate home treatment of patients
with VTE using a target-specific
oral anticoagulant that requires
minimal laboratory monitoring,”
Dr. Beam wrote. “[This initial
report] demonstrates that patients
can be treated at home with rivaroxaban with a low rate of VTE recurrence and low rate of bleeding.”
The single-arm protocol was
divided into two phases: an emergency department phase, which
included the actual VTE diagnosis,
and a follow-up clinic phase. Eligible patients were prescribed 15 mg
of rivaroxaban twice per day for 21
days, followed by one month of the
drug at 20 mg once per day.
In the follow-up phase, one to
two days after discharge, a member of the health-care team called
the patient to confirm that he or
September 2015