Therapeutics,
Год журнала:
2024,
Номер
1(2), С. 95 - 105
Опубликована: Ноя. 29, 2024
Background/Objectives:
Mantle
cell
lymphoma
(MCL)
represents
a
rare
B-cell
subtype
with
rather
high
relapse
rates.
Somatic
mutations
in
the
PPM1D
gene
were
shown
to
be
associated
adverse
outcomes
patients
diffuse
large
(DLBCL)
who
received
CD19
CAR-T-cell
therapy
tisa-cel,
which
may
also
apply
mantle
receiving
brexu-cel
CAR-T-cells.
Methods:
In
this
study,
we
determined
prevalence
of
peripheral
blood
cells
MCL
before
infusion
and
analyzed
impact
low-frequency
on
efficacy
safety
aspects
treatment
first
16
r/r
enrolled
at
Inselspital
Bern.
Results:
The
was
25%,
variant
allele
frequencies
(VAF)
0.011
0.099.
Clinical
response
mutated
(PPM1Dmut)
vs.
wild-type
(PPM1Dwt)
groups
median
progression-free
survival
1
versus
32
months
(p
=
0.07)
overall
1.5
27
0.001).
Conclusions:
Our
data
suggest
that
predict
inferior
treated
therapy.
Clinical Cancer Research,
Год журнала:
2024,
Номер
30(20), С. 4690 - 4700
Опубликована: Сен. 11, 2024
Abstract
Purpose:
Chimeric
antigen
receptor
(CAR)
T-cell
therapy
is
a
potent
immunotherapy
for
hematologic
malignancies,
but
patients
can
develop
long-term
adverse
events,
including
second
primary
malignancies
(SPM)
that
impact
morbidity
and
mortality.
To
delineate
the
frequency
subtypes
of
SPMs
following
CAR-T
in
lymphoma
myeloma,
we
performed
systematic
review
meta-analysis.
Experimental
Design:
A
literature
search
was
conducted
MEDLINE,
Embase,
Cochrane
CENTRAL
databases.
Following
extraction
SPM
cases
assignment
malignant
origin,
analyzed
point
estimates
using
random
effects
models.
Results:
We
identified
326
across
5,517
from
18
clinical
trials
7
real-world
studies.
With
median
follow-up
21.7
months,
overall
estimate
6.0%
(95%
confidence
interval,
4.8%–7.4%).
were
associated
with
treatment
setting
(clinical
>
studies),
duration
follow-up,
number
prior
lines,
which
each
confirmed
as
independent
study-level
risk
factors
meta-regression
model.
subgroup
meta-analysis
four
randomized
versus
standard-of-care
revealed
similar
either
strategy
(P
=
0.92).
In
distribution
analysis
subtypes,
most
common
entity
(37%),
followed
by
solid
tumors
(27%)
non-melanoma
skin
cancers
(16%).
represented
small
minority
events
(1.5%).
noted
disease-
product-specific
variations
distribution.
Conclusions:
These
data
raise
awareness
clinically
relevant
event
receiving
CAR
therapy.
However,
our
findings
do
not
indicate
higher
previous
strategies.
JAMA Oncology,
Год журнала:
2024,
Номер
10(6), С. 826 - 826
Опубликована: Апрель 18, 2024
This
cohort
study
assesses
the
increase
in
second
primary
malignant
neoplasms
and
T-cell
neoplasm
cases
associated
with
chimeric
antigen
receptor–T
cells.
Leukemia,
Год журнала:
2024,
Номер
38(6), С. 1378 - 1389
Опубликована: Апрель 18, 2024
Clonal
hematopoiesis
(CH)
driven
by
mutations
in
the
DNA
damage
response
(DDR)
pathway
is
frequent
patients
with
cancer
and
associated
a
higher
risk
of
therapy-related
myeloid
neoplasms
(t-MNs).
Here,
we
analyzed
423
serial
whole
blood
plasma
samples
from
103
relapsed
high-grade
ovarian
receiving
carboplatin,
poly(ADP-ribose)
polymerase
inhibitor
(PARPi)
heat
shock
protein
90
(HSP90i)
treatment
within
phase
II
EUDARIO
trial
using
error-corrected
sequencing
72
genes.
DDR-driven
CH
was
detected
35%
longer
duration
prior
PARPi
treatment.
TP53-
PPM1D-mutated
clones
exhibited
substantially
clonal
expansion
rates
than
DNMT3A-
or
TET2-mutated
during
Expansion
DDR
correlated
HSP90i
exposure
across
three
study
arms
partially
abrogated
presence
germline
related
to
homologous
recombination
deficiency.
Single-cell
selected
revealed
exclusivity
mutations,
identified
DDR-mutated
as
origin
t-MN
two
investigated
cases.
Together,
these
results
provide
unique
insights
into
architecture
preferential
selection
hematopoietic
under
intense
DNA-damaging
Specifically,
therapies
pose
an
independent
for
DDR-CH
dose-dependent
manner.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(17), С. 9518 - 9518
Опубликована: Сен. 1, 2024
Chimeric
antigen
receptor
(CAR)
T-cell
therapies
have
revolutionised
the
field
of
haematological
malignancies
by
achieving
impressive
remission
rates
in
patients
with
highly
refractory
malignancies,
improving
overall
survival.
To
date,
six
commercial
anti-CD19
and
anti-BCMA
CAR
products
been
approved
Food
Drug
Administration
(FDA)
for
treatment
relapsed/refractory
B-cell
multiple
myeloma.
The
indications
are
gradually
expanding,
these
being
investigated
a
variety
diseases,
including
non-malignant
ones.
Despite
great
success,
there
several
challenges
surrounding
therapies,
such
as
non-durable
responses
high-grade
toxicities.
In
addition,
new
safety
concern
was
added
FDA
on
28
November
2023
following
reports
previously
treated
either
or
autologous
both
clinical
trials
real-world
setting.
Since
then,
published
presenting
incidence
analysing
risks
other
secondary
after
therapies.
this
opinion
article,
current
landscape
is
presented,
along
proposed
strategy
future
research
aiming
at
potentially
diminishing
abrogating
risk
developing
