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PAPER SPOTLIGHT
Brentuximab Vedotin:
Changing the Landscape
for Relapsed/Refractory
Hodgkin Lymphoma
Patients?
For the approximately
50 percent of patients
with relapsed/refractory Hodgkin lymphoma
who do not respond to
autologous stem cell
transplantation (autoSCT), the antibody-drug
conjugate brentuximab
vedotin produced durable
response and survival,
according to results from
a pivotal phase 2 study
reported in Blood. The
observed median overall
survival (OS), the study
authors noted, is particularly promising because
these heavily treated
patients – who relapsed a
median of only 6.7 months
from their transplant – are
a particularly vulnerable
population.
Study investigators,
led by Ajay K. Gopal,
MD, from the University
of Washington and Fred
Hutchinson Cancer Research Center in Seattle,
evaluated the impact of
brentuximab vedotin on
survival and durability of
response in 102 patients
with relapsed/refractory
HL following auto-SCT.
Brentuximab vedotin
comprises an anti-CD30
antibody conjugated by a
protease cleavable linker
to monomethyl auristatin
E, a microtubule-disrupting agent.
Patients were followed for a median of
nearly three years (33.3
months) from their first
dose of the study drug.
FIGURE. Patients who remain in remission per the investigator
following treatment with brentuximab vedotin. Patients are
shaded according to their best response on treatment with brentuximab
vedotin. The two patients with a partial remission achieved a complete
remission following transplant.
ASHClinicalNews.org
Patients responded
quickly to the drug, with
a median time to first
response (assessed by
investigators) of 5.7
weeks and a median
time to complete response of 12.2 weeks.
Median OS and
progression-free survival
(PFS) were estimated
at 40.5 months and 9.3
months, respectively.
Notably, patients’ median PFS on brentuximab
vedotin was longer than
the median PFS on their
most recent prior therapy
– by a measure of more
than three months (9.3
months vs. 6.1 months).
Overall, 73 patients
(72%) achieved an
objective response, as
determined by the investigators – 34 patients
(33%) achieved complete
remission and 39 (38%)
achieved partial remission.
Achieving complete
remission on brentuximab vedotin appeared to
be critical for prolonged
disease control: for the
34 patients who achieved
a complete remission,
16 (47%) remained
progression-free after a
median of 53.3 months
of observation. Estimated three-year OS and
PFS rates in this group
were 73 percent (95% CI
57%-88%) and 58 percent (95% CI 41%-76%),
respectively, as well.
At the time of last
follow-up, 18 patients
were still on study and
in remission without
starting new therapy
(FIGURE). Of those, 15 had
been followed for more
than four years, or more
than a year after the
last progression event.
“Ongoing remissions of
more than four years are
particularly noteworthy
for a single agent in patients who had relapsed
or progressed after both
combination therapy and
auto-SCT,” Dr. Gopal and
colleagues wrote.
The investigato