Written in Blood
suggest that “elimination of MRD was
significantly associated with prolonged
CR duration (p<0.0001),” the authors
observed.
The authors assessed nine patients
for lymphocyte subsets before and
after treatment: Circulating HCL cells
cleared in all patients, but normal B
cells decreased by <50 percent in three
patients and increased in all others. T
cells and their subsets increased in all
but one patient, “thus, [the anti-CD22
drug] spared T cells and, with its short
half-life, avoided prolonged B-cell
depletion,” they noted.
“Moxetumomab pasudotox 50 µg/kg,
particularly with consolidation cycles,
cleared MRD in more than half of
[patients who experienced] CR,” the
authors wrote, noting that MRD clear-
ance was associated with improved
CR duration. Of the 29 patients who
received the 50 µg/kg dose, 22 (76%)
clearing MRD in the blood had higher
CR (n=19/22 vs. n=1/7; p=0.001) and
higher overall response rates (n=22/22
vs. n=4/7; p=0.01), compared with
those who never achieved MRD-
negativity.
Pharmacokinetics analysis in
29 evaluable patients revealed that
plasma concentrations of moxetu-
momab increased 213 percent during
cycle one (p<0.001) and increased
121 percent during cycle two from
days one to five (p=0.002). The
volumes of distribution and clear-
ances decreased, while soluble CD22
levels and HCL burden decreased,
per enzyme-linked immunosorbent
assays. These findings, the authors
noted, suggest “moxetumomab pasu-
dotox at 50 μg/kg achieved cytotoxic
plasma levels that increased with
rapid resolution of tumor burden and
were not completely blocked when
neutralizing antibodies were first
detectable.”
An ongoing multicenter, pivotal
study is assessing moxetumomab
pasudotox in patients with relapsed/
refractory HCL.
This early-phase study is limited
by its small patient population and
lack of a comparator arm.
MedImmune provided support for
the study.
Some of the authors are co-
inventors of immunotoxin patents
assigned to the government of the U.S.,
as represented by the secretary of the
Department of Health and Human
Services on behalf of the National
Institutes of Health, which are licensed
by MedImmune.
REFERENCE
Kreitman RJ, Tallman MS, Robak T, et al. Minimal residual hairy
cell leukemia eradication with moxetumomab pasudotox: phase
I results and long-term follow-up. Blood. 2018 February 27.
[Epub a