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Featured research from recent issues of Blood
PAPER SPOTLIGHT
Five-Year Follow-Up Shows
Response to Ibrutinib Deepens
Over Time for CLL Patients
Treatment with continuous,
single-agent ibrutinib led to
durable responses in patients
with chronic lymphocytic
leukemia (CLL), even among
previously untreated patients,
patients older than 65 years, and
those with TP53 mutations.
“In most cancers, with the
notable exception of chronic
myeloid leukemia, single-agent
therapy is limited by the rapid
emergence of drug resistance,”
wrote Inhye E. Ahn, MD, of
the National Heart, Lung, and
Blood Institute and co-authors
in a recent study published in
Blood. “Our data with extended
follow-up of patients on ibrutinib
suggests that a large proportion
of [patients with] CLL achieve
durable disease control on single-
agent ibrutinib, with excellent
tolerability.”
“With continuing the treat-
ment for almost five years, not
only were the remissions lasting,
but, in many cases, they improved
from partial to complete remis-
sions (CR), including some
patients who achieved minimal
residual disease (MRD) negativ-
ity,” Kanti Rai, MD, professor
at Donald and Barbara Zucker
School of Medicine at Hofstra/
Northwell Health, told ASH
Clinical News when asked for
comments on the study’s find-
ings. (Read more from Dr. Rai in
“Perspectives” at the end of this
article.)
The open-label, single-center
study enrolled 86 patients (me-
dian age = 66 years; range = 33-
85 years) between December 2011
and January 2014. Participants
had CLL or small lymphocytic
lymphoma that required therapy,
an Eastern Cooperative Oncology
Group performance status score
of ≤2, neutrophil count ≥500/µL,
and platelet count ≥30,000/µL.
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ASH Clinical News
Most patients were treatment-
naïve (n=53; 61.6%), had advanced
disease (Rai stage III/IV; n=58;
67.4%), and had unmutated
immunoglobulin heavy-chain
variable region gene (IGHV; n=57;
66.3%). The 33 patients (38.4%)
with relapsed/refractory disease
had been treated with up to seven
prior regimens.
Patients received ibrutinib 420 mg
once-daily until disease progres-
sion or unacceptable toxicity.
As of December 31, 2017
(data cutoff), 49 patients (57%)
remained on study after a median
of 4.8 years (range = 4-6 years).
Four patients (4.7%) died because
of infection (n=3) and cardiac
events (n=1). Twenty-five patients
discontinued ibrutinib because of
progressive disease (23.3%) or ad-
verse events (AEs; 5.8%). Six pa-
tients (7.0%) withdrew for various
other reasons, and two patients
did not meet the eligibility criteria
and were excluded.
AEs that led to treatment
discontinuation included asymp-
tomatic interstitial pulmonary
TABLE 1.
infiltrates, progressive multi-
focal leukoencephalopathy, and
persistent grade 3 diarrhea with
biopsy-confirmed microscopic
colitis (n=1 for each). Two patients
(2.3%) discontinued because of
second malignancies requiring
systemic therapy. Nine patients
(10.5%) required ibrutinib dose
reductions.
“The safety profile of con-
tinuous therapy with ibrutinib for
[more than] five years was simi-
lar to what has been reported
with shorter treatment duration,”
the researchers reported. “No
new safety signals emerged, and
most AEs were grade 1 or 2 and
transient.” The most common
treatment-related grade 3 or 4
hematologic AEs were neutrope-
nia (n=33; 38.4%), thrombocyto-
penia (n=13; 15.1%), and a