CLINICAL NEWS
were significantly lower than for inpatients
(median = $3,840 vs. $5,852; p<0.001)
despite increased charges per inpatient
day when readmitted (median = $7,405 vs.
$5,852; p<0.001),” the researchers reported.
“Early discharge following intensive AML
or MDS chemotherapy can reduce costs
and use of IV antibiotics,” the researchers
concluded, “but attention should be paid to
complications that may occur in the outpatient setting.” The single-center design is a
limitation of this study, and the safety signals
concerning, though, and the results will need
to be confirmed at additional centers before
this can be considered an acceptable, standard approach to treatment. ●
REFERENCE
Vaughn JE, Othus M, Powell MA, et al. Resource utilization and safety of
outpatient management following intensive induction or salvage chemotherapy
for acute myeloid leukemia or myelodysplastic syndrome: a nonrandomized
clinical comparative analysis. JAMA Oncol. 2015 September 10. [Epub ahead of
print]
Chimeric Antigen Receptor
T Cells Induce Sustained
Remissions for Minority of CLL
Patients
Although chronic lymphocytic leukemia
(CLL) remains incurable with conventional
therapies, recent studies examining the use of
chimeric antigen receptor (CAR)-modified
T cells targeting CD19 have induced durable
complete remissions (CR) in patients with
relapsed or refractory CLL, acute lymphocytic leukemia, and non-Hodgkin lymphoma.
These previous attempts to use CAR-modified
T cells were limited, however, by inadequate
in vivo expansion and minimal persistence.
Porter told ASH Clinical News. “The cells
can persist and remain functional beyond
three years following infusion. We now have
patients who have gone five years with no
evidence of leukemia by all measures, thus
suggesting that this approach has the potential to eradicate CLL even in patients with
advanced, heavily pretreated disease.”
In the study, which was published in
Science Translational Medicine, Dr. Porter
and colleagues presented mature results
from their pilot clinical trial of CTL019 in
14 patients with CLL.
Patients were infused
with autologous T
cells transduced with
a CD19-directed CAR
lentiviral vector at
doses of 0.14 x 108 to
11 x 108 CTL019 cells
(median = 1.6 x 108
cells). Twelve patients
were male, and the
median patient age
was 66 years (range =
51-78 years). Patients
had received a median
of five prior lines of
therapy (range = 1-11
—DAVID PORTER, MD
therapies), and eight
patients had del17p
CLL. All patients had active disease at the
time of CTL019 infusion.
The patients were monitored for toxicity,
response, in vivo expansion, and persistence
of circulating CTL019 T cells.
The median follow-up for all 14 patients
was 19 months (range = 6-53 months). The
overall response rate (ORR) was 57 percent
(n=8; 95% CI 29-82); 29 percent of patients
(n=4) reached complete remission and another 29 percent of patients (n=4) achieved
"The CTL019 cells expand
to high levels but also
persist for long periods of
time. ... This approach has
the potential to eradicate
CLL even in patients with
advanced, heavily pretreated disease.”
A new study by David Porter, MD, from
the division of hematology/oncology at
Abramson Cancer Center at the University of
Pennsylvania Perelman School of Medicine in
Philadelphia, Pennsylvania, demonstrated that
CAR-modified T cells lead to sustained remissions in those patients with heavily pretreated
CLL who achieved a CR to the treatment.
“We have found that the CD19-directed
CAR (CTL019) cells expand to high levels
but also persist for long periods of time,” Dr.
ASHClinicalNews.org
partial remission (PR) within the first month
following CTL019 infusion.
Among the four patients who achieved
CR, none of the patients experienced a relapse, with a median duration of response of
40 months (range = 21-53 months from time
of infusion). Among those who achieved PR,
the median duration of response was seven
months (range = 5-13 months).
Six patients (43%) had no response to
treatment and all six of these patients progressed within one to nine months (median
= 4 months). Minimal residual disease was
not detectable in patients who achieved CR,
which suggests that disease eradication may
be possible in some patient cohorts.
Median overall survival (OS) was 29 months,
with an 18-month OS of 71 percent (95% CI
40.6-88.2); estimated progression-free survival
(PFS) was seven months, with an 18-month PFS
of 28.6 percent (95% CI 8.8-52.4).
“We have not identified any pretreatment demographic or disease-related factors
to predict which patients are most likely to
respond [to CTL019 treatment],” the authors
wrote, adding that the study was not powered
to investigate these associations. There was
no distinction between responders and nonresponders according to patient age, number
of prior therapies, stage at enrollment,
del17p subtype, IgH variable mutation status,
or CTL019 dose (p>0.05 for all).
CTL019 infusions were well tolerated,
with mild (