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PAPER SPOTLIGHT
Frontline Brentuximab Vedotin
Leads to High Response Rate for
Older Hodgkin Lymphoma Patients
Patients received 1.8
mg/kg of brentuximab vedotin intravenously every
three weeks for up to 16
doses. Patients who demonstrated clinical benefit
could continue treatment
beyond 16 cycles until
disease progression, unacceptable toxicity, or study
closure. If toxicity occurred, dose reductions to
1.2 mg/kg and treatment
delay of up to three weeks
were allowed depending
on the type and severity
of toxicity.
Patients received a
median of eight cycles
of treatment, with four
patients completing 16
cycles and one completing
23 cycles.
Computed tomography and PET scans were
conducted at baseline, at
cycles 2 and 8, and again
at the end of treatment.
Of the 26 evaluable patients, the ORR was 92 percent (n=24), exceeding the
25 percent ORR considered
to represent a threshold
for clinical benefit in this
patient population. In addition, 73 percent
of patients
(n=17) achieved
TABLE 1. Best Clinical Response to Frontline Brentuximab Vedotin
CR and 19
Monotherapy
percent (n=5)
achieved partial
Number of patients
95% Confidence
remission.
(N=26)
Percentage
Interval
The remaining
Objective response rate
24
92%
74.9-99.1
two patients
(complete remission + partial remission)
achieved stable
Best clinical response
disease (TABLE
Complete remission
19
73%
52.2-88.4
1).
Partial remission
5
19%
N/A
At the time
Stable disease
2
8%
N/A
of analysis,
the median
Disease control rate
26
100%
86.9-100
Older patients with Hodgkin lymphoma (HL) tend to
have worse outcomes than
younger patients when
treated with conventional
chemotherapy regimens,
likely due to a different biology and a higher
comorbidity burden. In addition, this patient population tolerates conventional
initial therapy poorly – resulting in under-treatment
and making evaluation of
novel, less-toxic treatment
strategies necessary.
Previous studies of
brentuximab vedotin have
reported promising results
in older patient populations
with relapsed/refractory
HL, leading Andres ForeroTorres, MD, from the University of Alabama at Birmingham, and colleagues
to evaluate the efficacy
and safety of brentuximab
vedotin, a CD30-directed
antibody drug conjugate,
as frontline therapy in
patients 60 years or older
with classic HL.
“Although the incidence
of Hodgkin lymphoma is
elevated in individuals ≥65
38
ASH Clinical News
years old relative to younger patients and is expected
to increase by 70 percent
by 2030,” Dr. Forero-Torres
and authors observed, “few
clinical trials specifically
enroll older adults."
Twenty-seven patients
from 16 clinical sites in
the United States were
included in the phase II,
open-label study, with
74 percent (20 patients)
coming from communitybased sites. The median
age of patients was 78
years (range, 64-92 years);
17 patients were 75 years
of age or older, and five
patients were 85 years
or older. Most patients
had stage three or four
HL. Data were collected
on patients from October
2012 to March 2015; some
patients are still receiving
follow-up care.
All patients were
treatment-naïve and either
ineligible for frontline conventional chemotherapy or
had declined chemotherapy after being informed of
the potential benefits and
risks of treatment.
“Since chronologic age
alone does not capture
the heterogeneity present
within an elderly population, baseline geriatric assessment was conducted
to more fully characterize
the patients,” the authors
added, which included
an evaluation of physical function, comorbidities, nutritional status,
cognition, psychological
state, and social activity/
support.
The study’s primary
objective was to assess
the overall response rate
(ORR). Secondary objectives included duration of
response, complete remission (CR), progression-free
survival (PFS), resolution
of B symptoms, safety and
tolerability, and pharmacokinetics.
“Eighty-one percent of
patients were impaired in
at least one aspect including physical performance
problems,” the authors
noted, “[illustrating] the
relatively fragile condition
of the patients enrolled on
this study.”
duration of objective response was 9.1 months
(range = 2.8-20.9 months),
4.1 months for partial
remission (range = 3.9-10.3
months), and 9.2 months
for CR (range = 2.8-20.9
months). Median PFS was
10.5 months (range = 2.622.3), while median OS had
not been reached.
Most patients (89%) experienced treatment-emergent peripheral neuropathy
events. Other commonly
reported treatment-related
adverse events included
fatigue (44%) and nausea
(44%), both of which were
generally consistent with
the known safety profile of
brentuximab vedotin. However, the incidence of grade
three neuropathy events
was “relatively high,” at 30
percent overall – particularly
among patients with the
known risk factors of diabetes and/or hypothyroidism.
“Brentuximab vedotin
monotherapy may provide a
frontline treatment option
for older patients who are
unable to tolerate conventional multi-agent chemotherapy,” the authors concluded. There were some
limitations to note, though,
including the single-arm
and open-label (rather than
randomized and blinded)
design, the relatively small
number of patients in the
evaluable population.
“An attempt to improve response duration
is currently being tested
in additional treatment
arms in this ongoing study,
in which elderly Hodgkin
lymphoma patients receive
a combination of brentuximab vedotin with either
bendamustine or dacarbazine,” they added. ●
REFERENCE
Forero-Torres A, Holkova B, Goldschmidt J, et al.
Phase 2 study of frontline brentuximab vedotin
monotherapy in Hodgkin lymphoma patients
aged 60 years and older. Blood. 2015. [Epub
ahead of print]
September 2015