CLINICAL NEWS
• Non-transplantation: HR=0.95 (95%
CI 0.88-1.04; p=0.273)
Compared with control arms in the
included RCTs, patients in the IMiD-containing arms had statistically significantly
increased risks for developing grade 3/4
vascular events, including deep-vein
thrombosis and pulmonary embolism and
peripheral neuropathy (TABLE 2).
“Notably, an increased risk of grade
3/4 peripheral neuropathy was found
with thalidomide (risk ratio [RR] = 2.83;
95% CI 1.26-6.35; p=0.012) but not
lenalidomide (RR=1.94; 95% CI 0.665.77; p=0.231) maintenance therapy,”
the authors reported. “In contrast, an
increased risk of myelosuppression was
only prominent with lenalidomide but not
thalidomide.”
There was no observed increased risk
for developing second primary malignancies in patients receiving either IMiD-containing maintenance regimen; however,
the researchers did find that lenalidomide
was associated with a higher risk of developing secondary primary hematologic
malignancies (RR=2.10; 95% CI 1.08-4.09;
p=0.029) but not solid tumors (RR=1.23;
95% CI 0.54-2.80; p=0.628).
“Although largely safe, prolonged use
of IMiDs for maintenance therapy of
MM can lead to increased risks of several
adverse events,” Dr. Wang and colleagues
reported. “While measures can be taken
to prevent thromboembolism and other
common adverse events that are largely
manageable, increased risk of peripheral
neuropathy with thalidomide, and more
importantly increased risk for developing
second primary malignancies with lenalidomide, warrant serious consideration
when starting maintenance therapy with
these agents.”
There was a high degree of variation
among the included RCTs, which may
limit the generalizability of the meta-analysis results, the authors noted, including
differences in trial design, induction and
consolidation therapies, patient characteristics, and definition of survival outcomes.
There was also the possibility of publication bias in selecting trials for inclusion,
as only published trials were included and
some studies without sufficient data were
excluded.
“Our meta-analysis clearly showed
that IMiD-based maintenance therapy can
statistically significantly improve PFS but
not OS in MM regardless of AutoHCT
status,” Dr. Wang and authors concluded.
However, “another important question
that cannot be answered by our study
because of the lack of necessary data is
which patient population will benefit the
most from IMiD maintenance therapy.” ●
REFERENCE
Wang Y, Yang F, Shen Y, et al. Maintenance therapy with
immunomodulatory drugs in multiple myeloma: a meta-analysis and
systematic review. J Natl Cancer Inst. 2015;108:342.
ASHClinicalNews.org
The BRAF Inhibitor
Vemurafenib “Highly Effective”
in Relapsed/Refractory HairyCell Leukemia
The oral BRAF inhibitor vemurafenib produced
high overall response rates, with mild toxicity,
in patients with relapsed or refractory hairy-cell
leukemia, according to a report from two phase
II studies published in The New England Journal
of Medicine.
Though purine analogues (such as cladribine
and pentostatin) induce durable complete responses in approximately 80 percent of patients
with this cancer, the authors, led by Enrico
Tiacci, MD, from the University of Perugia in
Italy, explained that 30 to 50 percent of patients
eventually relapse and experience a progressively
worse response to these drugs.
Previous research has shown that the
V600E mutation of BRAF is a key genetic lesion of hairy-cell leukemia leading, in part,
to the development of the BRAF inhibitor
vemurafenib. To test the safety and efficacy of
this oral medication, Dr. Tiacci and colleagues
conducted two phase II, multicenter clinical trials (one in Italy, the other in the United
States) in patients with relapsed or refractory
hairy-cell leukemia.
Patients received oral vemurafenib (960 mg
twice-daily) for a minimum of eight weeks and
up to 16 weeks (in the Italian trial) or 12 weeks
(in the U.S. trial).
The Italian trial enrolled 28 patients; 26 patients completed the planned treatment course,
with a median treatment duration of 16 weeks
(range = 8-20 weeks). Twenty-six patients had
been enrolled in the U.S. trial (out of a planned
enrollment of 36 patients) at the time the paper
was published; though enrollment was ongoing,
the primary endpoint of overall response rate
(ORR; including complete and partial responses)
had already been met, the authors noted.
After a median follow-up of 23 months in
the Italian trial and 11.7 months in the U.S.
trial, the ORRs were 96 percent and 100 percent,
respectively.
“The rates of complete response [CR] were
similar in the two trials, as were the rates of
partial response [PR],” Dr. Tiacci and colleagues
wrote. “In the Italian study, after a median of eight
weeks, 35 percent of the patients (9 of 26) had a
CR and 62 percent (16 of 26) had a PR. In the U.S.
trial, after 12 weeks of vemurafenib treatment, 42
percent of the patients (10 of 24 patients) had a
CR and 58 percent (14 of 24) had a PR.”
These responses were rapid, with a median
time to response of 8 weeks in the Italian trial
and 12 weeks in the U.S. trial, the authors added.
The median treatment-free survival was 21.5
months in the evaluable 26 patients in the Italian
trial, while the median relapse-free survival was
nine months. Patients w