On Location ASH Annual Meeting
blasts,” Dr. Uy explained.
He shared findings from the initial
dose-escalation phase of the study, which
enrolled 45 patients (40 with AML and
5 with MDS) whose disease had failed to
respond or relapsed after treatment with
conventional cytotoxic chemotherapy.
The median age of the entire cohort was
64 years (range not provided).
Participants were treated with
flotetuzumab at varying doses (3-1,000
ng/kg/day) in 28-day cycles on one of
two dosing schedules: four days on/
three days off or seven days on. To
mitigate cytokine release syndrome
(CRS), patients received lead-in doses of
flotetuzumab during week one of cycle
one, followed by a target dose (300-
1,000 ng/kg/day) on either of the dosing
schedules. If clinically indicated, CRS
was managed with steroid-sparing, anti-
cytokine therapy.
At the time of data presentation, the
maximum tolerated dose and schedule
were identified as 500 ng/kg/day.
Toxicity has been manageable, the
authors reported. Infusion-related reac-
tions and CRS were the most common
adverse events (AEs; n=34/45; 76%), and
grade ≥3 flotetuzumab-related AEs were
observed in 20 patients (44%).
“With any T-cell redirecting thera-
pies, including bispecific antibodies and
chimeric antigen receptor T cells, CRS
is a potentially severe and dose-limiting
toxicity,” Dr. Uy said. “We found that CRS
could be managed with either temporary
interruption of flotetuzumab or admin-
istering steroids or the interleukein-6
antibody tocilizumab.”
Of the 45 patients, 14 treated with
500 to 700 ng/kg/day have completed at
least one cycle of treatment and received
a post-treatment bone marrow biopsy.