CLINICAL NEWS
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Featured research from recent issues of Blood
PAPER SPOTLIGHT
Brentuximab Vedotin Plus CHP
Leads to Lasting Remissions in
Peripheral T-Cell Lymphomas
Half of patients with peripheral T-
cell lymphomas (PTCLs) who were
treated with brentuximab vedotin
in combination with CHP (cyclo-
phosphamide, doxorubicin, pred-
nisone) remained in remission for
almost five years, according to
long-term follow-up from a phase
I trial of this frontline regimen. 1
The report, published in
Blood by Michelle A. Fanale, MD,
of the University of Texas MD
Anderson Cancer Center, updates
previously published findings, in
which all 26 participants re-
sponded to brentuximab vedotin
plus CHP. The initial trial protocol
evaluated both CHP and CHOP
(cyclophosphamide, doxorubicin,
vincristine, prednisone) but,
because a high number of par-
ticipants had disease progression
while receiving CHOP, enrollment
in this arm was terminated. 2
The study included 26 treatment-
naïve patients (median age = 55.5
years; range = 21-82 years) with
CD30-positive PTCL; 19 (73%) had
systemic anaplastic large-cell
lymphoma (ALCL; including 16
with ALK-positive disease) and
the remaining seven (27%) had
other CD30-positive PTCLs.
Per study protocol, participants
received brentuximab vedotin 1.8
mg/kg and standard-dose CHP
every three weeks for six cycles. If
patients experienced an objective
response, they received up to 10
cycles of brentuximab vedotin as a
single agent.
After receiving a median of
13 cycles (range = 3-16 cycles) of
brentuximab vedotin, all patients
(100%) achieved an objective
response, including 24 complete
remissions (CRs; 92%) and two
partial remissions. After a median
follow-up of 59.6 months (range
= 4.6-66.0 months), 12 patients
(46%) experienced progressive
disease or died, including 10 with
ALCL (the other 2 patients had
non-ALCL disease).
ASHClinicalNews.org
Five patients (19%) died dur-
ing long-term follow-up (4 with
ALK-negative ALCL and 1 with
enteropathy-associated T-cell
lymphoma); four deaths were
disease-related and the other
was caused by respiratory failure.
“No progression or death was
observed beyond 35 months,” the
researchers reported.
Among the patients whose
disease progressed, eight (31%)
received subsequent therapy:
three (38%) underwent hemato-
poietic cell transplantation and
four (50%) received initial single-
agent brentuximab vedotin.
After approximately five years
of follow-up, 13 patients (50%)
remained in remission without
receiving any new anti-cancer
therapy; all had achieved CR,
including nine with systemic ALCL
(3 with ALK-positive disease) and
four with other diagnoses. In this
cohort, progression-free survival
values ranged from 37.8 months
to more than 66 months.
The long-term results of this
phase I study are “very encourag-
ing,” Laurie H. Sehn, MD, MPH,
told ASH Clinical News when
asked for comment on the study’s
findings. However, she added that
the findings “will require further
validation within the context of a
randomized controlled trial before
[frontline brentuximab vedotin
plus CHP] is routinely used in
clinical practice.” (Read more from
Dr. Sehn in “Perspectives” at the
end of this article.)
The median overall survival (OS)
was not reached during follow-up;
the estimated five-year OS was
79 percent (95% CI 53-92) for pa-
tients with ALCL and 83 percent
(95% CI 27-97) for patients with
non-ALCL disease. Those with
ALK-positive disease appeared to
have more favorable outcomes
than those with ALK-negative
ALCL, the researchers noted.
Among patients still in remission
at last follow-up, disease stage at
diagnosis tended to be earlier and
baseline International Prognostic
Index score tended to be lower.
Those remaining in remission
received a median of 16 treatment
cycles (range = 6-16 cycles), com-
pared with 10 cycles (range = 3-16
cycles) for those who were not in
remission.
Nineteen patients, including
12 who remained in remission,
experienced treatment-related
peripheral neuropathy, which is a
known adverse event associated
with brentuximab vedotin. At last
follow-up, 10 participants (53%)
had ongoing peripheral neu-
ropathy. Most cases of peripheral
neuropathy were grade 1 or 2
(n=17), but two patients expe-
rienced a grade 3 reaction. The
median time to onset of peripheral
neuropathy was 11 weeks (range
= 0-34 weeks), and almost all
patients (n=18; 95%) had resolu-
tion or improvement in peripheral
neuropathy symptoms during
treatment (within a median of 4.2
months and 2.6 months, respec-
tively; ranges not provided). Nine
patients had full resolution.
The study is limited by its
small patient population and lack
of a comparator arm. Based on
the results of this study, inves-
tigators initiated a randomized,
phase III trial comparing frontline
brentuximab vedotin plus CHP
and brentuximab vedotin plus
CHOP for patients with PTCL. The
authors expect the results to be
published soon.
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