ASH News Daily - Monday, December 12, 2011 - (Page A-2)
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AML
Gemtuzumab Ozogamicin: Miraculous Recovery
Or Late Rally Before (Ultimate) Death?
By Michael r. BiShop, Md
mended that anti-CD33 immunotoxin
gemtuzumab ozogamicin, which
had received accelerated approval
for the treatment of acute myeloid
leukemia (AML), should no longer
be commercially available to new
patients. The recommendation was
based on the results of the Southwest
Oncology Group trial, SWOG
S0106, which had raised concerns
about the safety,
specifically hepatotoxicity,
and clinical
efficacy of gemtuzumab
ozogamicin.
On the same day,
Pfizer Inc., the parent
company that
produced gemtuzumab
ozogamicin,
announced that it
would be discontinuing
commercial
availability of gemtuzumab
ozogamicin
in the United States, as well as
voluntarily withdrawing a new drug
application for the agent. However,
the subsequent reported results of a
number of studies, most notably the
MRC AML15 trial, suggested a potential
survival advantage with the
addition of gemtuzumab ozogamicin.
Despite these promising results
in selected AML populations, there
appeared to be very little hope that
there would be continued sponsorship
of trials involving gemtuzumab
ozogamicin.
In Sunday’s Plenary Scientific
session, we were presented with
O
n June 21, 2010, the United
States Food and Drug Administration
(FDA) recom-
However, they
hypothesized that the
toxicity could be
reduced and the efficacy
enhanced by using re-
peated and small doses
of gemtuzumab
ozogamicin.
additional data supporting the efficacy
of gemtuzumab ozogamicin
in the treatment of AML, as Dr.
Sylvie Castaigne, representing the
Acute Leukemia French Association
(ALFA), presented the results
of a prospective randomized (0701)
phase 3 trial (ALFA 0701) of fractionated
doses of gemtuzumab ozogamicin
in combination with standard
chemotherapy for newly diagnosed
de novo AML patients between the
ages of 50 and 70 years. Dr. Castaigne
shared with ASH News Daily that she
and her colleagues were quite aware
that “there exists a
thin gap between efficacy
and toxicity”
with the use gemtuzumab
ozogamicin.
However, they
hypothesized that
the toxicity could
be reduced and the
efficacy enhanced
by using repeated
and small doses of
gemtuzumab ozogamicin.
After preliminary
testing of
this hypothesis in phase II studies
for relapsed AML, they moved forward
to design and conduct ALFA
0701. Patients were randomized to
receive a standard induction regimen
of daunorubicin and cytosine
arabinoside given in a standard
“3+7” manner (“DA” arm) or to receive
the same regimen plus gemtuzumab
ozogamicin given at a dose of
3 mg/m2
on days 1, 4, and 7 of treat-
ment (“DAGO” arm). A total of 280
patients were enrolled in the study.
Complete remissions were achieved
in 75 percent in the DA arm, while 80
percent of patients achieved a CR on
ASH NEWS DAILY
Monday, December 12, 2011
Dr. Sylvie Castaigne presents the final abstract in the Plenary Scientific session.
the DAGO arm. There was no significant
difference in deaths (4 vs. 6%)
between the two arms. There was
a highly significant advantage in
event-free and disease-free survival
at two years for patients who were
treated on the DAGO arm. More
importantly, this translated into a
10-month overall survival advantage
for DAGO.
The investigators concluded that
the data from ALFA 0701 demonstrated
a clear benefit in event-free
survival, overall survival, and remission
duration for patients treated in
the DAGO arm. Plenary Introducer
Dr. Martin Tallman, Memorial SloanKettering
Cancer Center, commented
BMT
«« From Page A-1
He went on to explain that
causes of treatment failure were
also different in the two groups.
More graft failure (8% vs. none
in PBSC) and infection occurred
in the marrow group, whereas
more chronic and severe GVHD
occurred in the BM group.
Dr. Armand Keating, soon-to-
be-minted president of ASH and
former president of the American
Society of Blood and Marrow
Transplantation, commented
on the significance of this study:
“This is an impressive achievement
by BMT-CTN, an important
milestone in transplantation …
the results suggest the need to reassess
which patients will benefit
from PBSC versus BM unrelated
transplantation, including an evaluation
of quality-of-life issues.”
Indeed, this study sheds fur-
ASH President Dr. J. Evan Sadler presents Dr. David G. Nathan with the Wallace
H. Coulter Award for Lifetime Achievement in Hematology.
ther light on the importance of individualizing
the choice of graft
that “This does not change the standard
of care for this patient population;
however, it does suggest that
gemtuzumab warrants further investigation.”
These data further perpetuate
the ongoing debate on the use of
gemtuzumab ozogamicin for the
treatment of AML. Given the paucity
of new agents that have proven efficacy
in AML, it is truly hoped that
these data will provide a new life for
gemtuzumab ozogamicin, which has
been clinging to life support these
past years after being given up for
dead in the United States.
Dr. Bishop indicated no relevant
conflicts of interest.
source in patients undergoing
transplant. PBSC may be preferred
in patients with little previous
cytotoxic chemotherapy,
who are at greater risk of marrow
failure. It may also be beneficial in
patients who require more rapid
engraftment, such as those at high
risk of infection. By contrast, BM
may be preferred in patients with
better marrow function at time of
transplant.
Further studies and longer-term
analysis will dictate the precise role
of both modalities in patients undergoing
transplant. In the interim,
Dr. Anasetti stated plainly, “This
study shows no survival differences
between the arms, and therefore
both sources are acceptable.” As a
result, it is likely that both sources
of grafts will continue to play a
role in unrelated transplants, and
you just may see more of your colleagues
in the OR at harvest time.
Dr. Mikhael indicated no relevant
conflicts of interest.
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