survival 0.721 [95% CI 0.443–1.173]; differ-
ence not significant).
Other secondary endpoints including
complete response rate, overall response
rate at the end of the randomization reg-
imen, complete response rate at the end
of front-line therapy, rate of PET negativity
at the end of cycle 2, duration of response,
duration of complete response, and
event-free survival, also trended in favor
of A + AVD.
The median treatment duration and num-
ber of completed cycles were similar
across treatment arms.
Safety profiles were consistent with the
known toxicities of the single agents.
Neutropenia was reported in 58% of
patients receiving A + AVD and 45%
receiving ABVD (febrile neutropenia in
19% and 8%, respectively).
The incidence of discontinuations due to
neutropenia or febrile neutropenia was
≤1% in both arms. Grade ≥3 infections
were more common in the A + AVD arm
(18%) than the ABVD arm (10%).
In patients receiving A + AVD, primary
prophylaxis with granulocyte-colony
stimulating factor (n=83) reduced febrile
neutropenia from 21% to 11% and grade ≥3
infections and infestations from 18% to 11%.
Peripheral neuropathy occurred in 67%
of patients receiving A + AVD and 43%
of those receiving ABVD (grade ≥3: 11%
A + AVD [one patient with grade 4] vs 2%
ABVD). Of patients experiencing periph-
eral neuropathy in the A + AVD arm, 67%
experienced resolution or improvement
of peripheral neuropathy at last follow-up.
Pulmonary toxicity was more frequent
and more severe with ABVD (grade ≥3:
3% ABVD vs <1% A + AVD). Of on-study
deaths, 7 of 9 in the A + AVD arm were
associated with neutropenia.
These deaths occurred in patients who
had not received primary prophylaxis with
granulocyte-colony stimulating factor. Of
13 on-study deaths in the ABVD arm, 11
were due to or associated with pulmonary
toxicity.
Dr. Connors concluded that, compared
with standard ABVD, A + AVD as frontline
therapy improved outcomes for patients
with advanced Hodgkin’s lymphoma,
including a 23% risk reduction in pro-
gression, death, or need for additional
anticancer therapy.
This result establishes A + AVD as a
new frontline option for patients with
advanced-stage Hodgkin’s lymphoma.
Dr. Connors remarked in an ASH press
release, “The experimental combination
with brentuximab vedotin got rid of all
the disease more frequently, and this
was achieved with acceptable levels of
adverse effects. Treatment with brentux-
imab vedotin was modestly more toxic,
but when we added simple measures to
improve patients’ blood counts, they were
able to take it safely.”
He continued, “We expect ABVD to cure
about three-quarters of patients, which
means, of course, that one-quarter will not
be cured. In this study, we were able to
reduce that rate of treatment failure sig-
nificantly. If this new regimen is adopted
widely, it will change first-line treatment of
advanced Hodgkin’s lymphoma.”
www.practiceupdate.com/c/61705ASH 2017 • PRACTICEUPDATE CONFERENCE SERIES
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