CLINICAL NEWS
Literature Scan
also less for those taking standard-dose
imatinib: 76 percent compared with 86
percent of the imatinib 800 mg group,
90 percent of the dasatinib group, and
91 percent of the nilotinib group. These
findings were consistent over time, the
investigators noted.
Five-year event-free survival also differed significantly between the imatinib 400
mg group and other TKI groups (compared
to imatinib 800 mg, p=0.029; dasatinib,
p=0.003; nilotinib, p=0.031).
In multivariate analysis, treatment with
higher-dose imatinib (HR=0.51; p=0.016),
dasatinib (HR=0.28; p=0.004), and nilotinib (HR=0.42; p=0.024) was associated
with better event-free survival compared
with standard-dose imatinib. However,
rates of failure-free, transformation-free,
and overall survival were similar irrespective of the TKI used.
Investigators also found that it took
longer for patients taking imatinib 400
“Long-term outcomes
of higher-dose imatinib
is similar to secondgeneration TKIs.”
—PREETESH JAIN, MD
mg to achieve a complete cytogenetic
response and major molecular response
compared to the other groups.
“Our analysis shows that long-term
outcomes of higher-dose imatinib is similar to second-generation TKIs,” Dr. Jain
told ASH Clinical News. “Therefore, in
situations where newer TKIs are beyond
the reach of patients, imatinib 800 mg
can be used without compromising the
outcomes – provided the patients are able
to tolerate it.”
The most significant finding of the
study, Dr. Jain noted, is that all four
treatment options achieved excellent
results with no significant difference in
overall survival among the groups, giving
physicians more flexibility as they try to
match the best medication with individual
patients.
“Treatment selection for an individual patient is a complex decision that
is affected by multiple factors, including
availability, cost, familiarity with the drug,
schedule of administration, risk factors
for certain expected adverse events with a
given agent, and others,” Dr. Jain said. ●
Reference
• Jain P, Kantarjian H, Alattar ML, et al. Long-term molecular and
cytogenetic response and survival outcomes with imatinib 400 mg,
imatinib 800 mg, dasatinib, and nilotinib in patients with chronicphase chronic myeloid leukaemia: retrospective analysis of patient data
from five clinical trials. Lancet Haematol. 2015;2:e118-e128.
32
ASH Clinical News
Ruxolitinib: Another Option
for Polycythemia Vera Patients
with Poor RESPONSE
Patients with polycythemia vera who do not
achieved hematocrit control and were able to
respond well to hydroxyurea may have another
reduce spleen volume by at least 35 percent
promising treatment option, according to results
(FIGURE; p<0.001).
from the RESPONSE trial.
Complete hematologic remission was also
A recent phase 3 trial found that ruxolimore common in patients taking ruxolitinib
tinib, a Janus kinase (JAK) 1 and 2 inhibitor,
(24%) compared to those on standard therapy
was superior to standard therapy in controlling
(9%; p=0.003).
hematocrit levels, reducing spleen volume, and
Patients taking ruxolitinib also reported
improving polycythemia vera symptoms for
fewer overall symptoms related to polycythemia
patients who either had an inadequate respo nse
vera, including itching, fatigue, and night sweats.
to hydroxyurea or had experienced unacceptable
After 32 weeks, 49 percent of patients taking
side effects.
ruxolitinib saw at least a >50 percent reduction
These findings, which were published in The
in their symptom score (as measured by the
New England Journal of Medicine, could provide
Myeloproliferative Neoplasm Symptom Assessa treatment alternative for the approximately 25
ment Form) versus 5 percent of patients in the
percent of polycythemia vera patients who don’t
standard therapy group.
respond well to hydroxyurea – the most comNearly 85 percent of patients assigned to
monly used cytoreductive drug used to treat the
ruxolitinib continued to receive it at a median
disease.
follow-up of 81 weeks, adding further support to
“This is the first time a drug has been evaluits tolerability.
ated in a controlled
study specifically
in this category of
FIGURE. Percentage of Patients Meeting the
patients that have
Primary Endpoints at Week 32
an advanced form
of disease with
dismal outcome,”
Alessandro M.
Vannucchi, MD,
the study’s first
author, told ASH
Clinical News.
In the RESPONSE trial,
investigators
randomly assigned
222 adult patients
with polycythemia
vera to receive
either ruxolitinib
(n =110) or another single-agent
therapy determined by their treating physician
With the ongoing RESPONSE trial, Dr.
as the best available therapy (n = 112). For the
Vannucchi said, investigators hope to learn
majority of patients, this was hydroxyurea (given more about how long ruxolitinib remains efto 58.9% of patients), followed by interferon
fective in controlling the disease. “Although
(given to 11.6% of patients).
ruxolitinib was very well-tolerated,” Dr. VanPatients in the ruxolitinib group received a
nucchi noted, “there was an apparent increase
starting dose of 10 mg twice daily. At week 32 of
of non-melanoma skin cancers and an increase
the study, researchers used MRI or CT scans to
of herpes virus reactivation in the randomized
evaluate the proportion of patients who had both phase. These events will be followed carefully
hematocrit control and a ≥35 percent reduction
over longer follow-up.” ●
in spleen volume compared to baseline.
Reference
In the ruxolitinib group, 21 percent of pa• Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard
tients achieved both hematocrit control and the
therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372:426-35.
reduction in spleen volume by week 32; however,
only 1 percent of those in the standard therapy
group had achieved both measures (FIGURE).
When the outcomes were looked at individually, investigators reported that significantly more patients in the ruxolitinib group
Month 2015