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PAPER SPOTLIGHT
Brentuximab Vedotin Leads
to Long-Term Remissions in
Patients with Relapsed/
Refractory Hodgkin Lymphoma
Magnified and artificially
dyed slide of lymph gland
tissue.
20
ASH Clinical News
In 2011, the U.S. Food and
Drug Administration approved the CD30 antibodydrug conjugate brentuximab
vedotin for the treatment of
patients with Hodgkin lymphoma (HL) whose disease
has progressed after autologous hematopoietic cell
transplantation (AHCT) or
two prior therapies. Approval
was based on the results
of an international, openlabel, phase II study of 102
patients with HL, in which
the complete response (CR)
rate was 34 percent (95% CI
25.2-44.4) and the objective
response rate (ORR) was 75
percent (95% CI 64.9-82.6).1
In a study published
in Blood, Robert Chen,
MD, from the City of Hope
National Medical Center in
Duarte, California, and colleagues report the five-year,
end-of-study results of this
pivotal trial, finding that
brentuximab vedotin led to
an estimated five-year overall survival (OS) rate of 41
percent and a progressionfree survival (PFS) rate of 22
percent.2
“In the pre-brentuximab
vedotin era, options were
limited and outcomes were
poor for HL patients who
relapsed or progressed
after AHCT, with median
OS ranging from 10.5 to
27.6 months,” Dr. Chen and
colleague wrote. “Given that
the historical outcomes
are poor for HL patients
who relapse after AHCT,
these results provide a new
perspective on prognosis for
this patient population in the
brentuximab vedotin era.”
The trial included 102
patients with relapsed/refractory HL (median age = 31
years; range = 15-77 years)
who were enrolled at 25
centers in the United States,
Canada, and Europe between
February and August 2009.
Patients were heavily pretreated, with a median number of prior regiments (other
than AHCT) of 3.5 (range =
1-13 regimens). Sixty-six
percent of patients received
prior radiation therapy, and
all patients underwent AHCT.
The median time to relapse
after AHCT was 6.7 months
(range = 0-131 months),
and the majority of patients
(71%) experienced relapse
within a year of undergoing
AHCT.
Patients received 1.8
mg/kg of brentuximab
vedotin administered intravenously over 30 minutes
once every three weeks for
up to 16 treatment cycles.
One-third of all patients
(n=34/102) achieved a CR,
with a median response duration that was not reached
(95% CI 20.5-not reached).
Within this group, the estimated five-year OS and PFS
rates were 64 percent (95%
CI 48-80) and 52 percent
(95% CI 34-69), respectively.
Of the 34 patients who
achieved a CR, six underwent
consolidative allogeneic HCT
(alloHCT) as the next therapy
after brentuximab vedotin.
These six patients had estimated five-year OS and PFS
rates of 83 percent (95%
CI 54-100) and 67 percent
(95% CI 29-100), compared
with 60 percent (95% CI 4178) and 48 percent (95% CI
28-68), respectively, among
the 28 patients who did not
undergo HCT.
At the time of study
closure, approximately five
years from the last patient’s
end-of-treatment visit, 15
patients remained on the
study and in remission without salvage therapy other
than alloHCT. Thirteen of
these patients achieved CR
(having received a median of
14 cycles of treatment), and
two achieved a partial response (PR; having received
a median of 6.5 cycles). For
these 13 patients:
• median OS was 40.5
month s (95% CI 28.761.9)
• median PFS was 9.3
months (95% CI 7.112.2)
• estimated 5-year OS
was 41% (95% CI 31-51)
• estimated 5-year PFS
rates was 22% (95% CI
13-31)
A majority of the study patients (75%; n=77) received
at least one anti-cancer
therapy following brentuximab vedotin: 45 received
multi-agent therapy, 42 received single-agent therapy,
and 22 underwent HCT (8 of
whom received consolidative
allogeneic HCT).
Thirteen of these 77 patients received retreatment
with brentuximab vedotin
(10 as single-agent, 3 as
multi-agent), and six were
treated with a PD-1 pathway
inhibitor (5 as single-agent, 1
as combination therapy).
Of the 13 complete
responders who remained
in remission at five-year
follow-up, four underwent
consolidative alloHCT, while
nine (26% of all CR patients) received no further
treatment. “The notion
that alloHCT with reducedintensity conditioning is the
only option for long-term
disease control is challenged,” the authors noted.
“Nine percent (n=9/102) of
the enrolled study population
has achieved long-term remission exceeding five years
in response to single-agent
brentuximab vedotin without
any additional therapy.”
The most commonly reported adverse event associated with cumulative exposure to brentuximab vedotin
was peripheral neuropathy
(PN; 55%; n=56). Most of
the patients experiencing PN
(88%; n=49) had resolution
or improvement, with 73
percent (n=41) reporting
complete resolution and
14 percent (n=8) reporting
some improvement at last
follow-up. Overall, Dr. Chen
and colleagues found “the
reported toxicities [to be]
manageable.”
“These results provide a new perspective on
prognosis for this patient
population,” the authors
concluded. “Among patients
with relapsed/refractory HL,
a substantial fraction of patients who obtained CR with
single-agent brentuximab
vedotin have achieved longterm disease control and
may be potentially cured.”
Though the authors
noted that treatment with
brentuximab vedotin improved upon the historically
poor outcomes for patients
with relapsed/refractory HL,
there was no comparator
arm in this trial. Also, though
the five-year OS and PFS
rates were high for patients
who underwent consolidative alloHCT, further studies
are needed to identify which
patients could benefit from
this therapy after receiving
brentuximab vedotin.
REFERENCES
1. Younes A, Gopal AK, Smith SE, et al. Results
of a pivotal phase II study of brentuximab
vedotin for patients with relapsed or
refractory Hodgkin’s lymphoma. J Clin
Oncol. 2012;30:2183-89.
2. Chen R, Gopal AK, Smith SE, et al. Fiveyear survival and durability results of
brentuximab vedotin in patients with
relapsed or refractory Hodgkin lymphoma.
Blood. 2016. [Epub ahead of print]
August 2016