CLINICAL NEWS
spleen volume, liver volume, blood platelet
count, and red blood cell level, compared
with placebo. In the second trial, eliglustat
resulted in similar stabilization of hemoglobin level, platelet count, and spleen and liver
volume as the enzyme replacement therapy
imiglucerase. The most commonly observed
side effects with eliglustat were fatigue,
headache, nausea, diarrhea, back pain, pain
in extremities, and upper abdominal pain.
Source: FDA News Release. Accessed from www.fda.gov/NewsEvents/
Newsroom/PressAnnouncements/ucm410585.htm
Google Searches for
Cancer and Heart
Attack Detector
The Google X research lab has set its sights
on designing tiny magnetic particles to
patrol the human body for signs of cancers
and other diseases. The announcement was
made at The Wall Street Journal’s WSJD Live
conference. At less than one-thousandth the
width of a red blood cell, these nanoparticles
would seek out and attach themselves to
cells, proteins, or other molecules inside the
body. The company also is working on a
wearable device with a magnet to attract and
count the particles, as a monitoring tool.
The goal is to provide an early warning system for cancer and other diseases.
According to Andrew Conrad, PhD, head
of the Life Sciences team at the Google X
research lab, the dream is to have “every test
you ever go to the doctor for done through
this system.” The reality, though, is more
than five years off, industry experts say.
Questions about how the nanoparticles
will be delivered, as well as regulatory
issues, remain. To those concerned about
patient information security, Dr. Conrad
said Google will not collect or store medical data itself. Instead, Google plans to
license the technology to others who will
handle the information and its security.
Source: The Wall Street Journal, October 29, 2014
T:7”
In the pooled MM trials Grade 3 and 4 hematologic toxicities were more
frequent in patients treated with the combination of REVLIMID and
dexamethasone than in patients treated with dexamethasone alone [see
Adverse Reactions (6.1)].
In the MCL trial, Grade 3 or 4 neutropenia was reported in 43% of the
patients. Grade 3 or 4 thrombocytopenia was reported in 28% of the patients.
5.4 Venous and Arterial Thromboembolism
Venous thromboembolic events (deep venous thrombosis and pulmonary
embolism) and arterial thromboses are increased in patients treated with
REVLIMID. A significantly increased risk of DVT (7.4%) and of PE (3.7%)
occurred in patients with multiple myeloma who were treated with
REVLIMID and dexamethasone therapy compared to patients treated in
the placebo and dexamethasone group (3.1% and 0.9%) in clinical trials
with varying use of anticoagulant therapies [see Boxed Warning and
Adverse Reactions (6.1)].
Myocardial infarction (1.7%) and stroke (CVA) (2.3%) are increased in
patients with multiple myeloma who were treated with REVLIMID and
dexamethasone therapy compared to patients treated with placebo and
dexamethasone (0.6%, and 0.9%) in clinical trials [see Adverse Reactions
(6.1)]. Patients with known risk factors, including prior thrombosis, may
be at greater risk and actions should be taken to try to minimize all
modifiable factors (e.g. hyperlipidemia, hypertension, smoking)
In controlled clinical trials that did not use concomitant thromboprophylaxis,
21.5% overall thrombotic events (Standardized MedDRA Query Embolic
and Thrombotic events) occurred in patients with refractory and relapsed
multiple myeloma who were treated with REVLIMID and dexamethasone
compared to 8.3% thrombosis in patients treated with placebo and
dexamethasone. The median time to first thrombosis event was 2.7 months.
Thromboprophylaxis is recommended. The regimen of thromboprophylaxis
should be based on an assessment of the patient’s underlying risks. Instruct
patients to report immediately any signs and symptoms suggestive of
thrombotic events. ESAs and estrogens may further increase the risk of
thrombosis and their use should be based on a benefit-risk decision in
patients receiving REVLIMID [see Drug Interactions (7.3)].
5.5 Increased Mortality in Patients with CLL
In a prospective randomized (1:1) clinical trial in the first line treatment
of patients with chronic lymphocytic leukemia, single agent REVLIMID
therapy increased the risk of death as compared to single agent chlorambucil.
In an interim analysis, there were 34 deaths among 210 patients on the
content
REVLIMID treatment arm compared to 18 deaths among 211 patients in
the chlorambucil treatment arm, and hazard ratio for overall survival was
1.92 [95% CI: 1.08 – 3.41], consistent with a 92% increase in the risk of
death. The trial was halted for safety in July 2013.
Serious adverse cardiovascular reactions, including atrial fibrillation,
myocardial infarction, and cardiac failure occurred more frequently in the
REVLIMID treatment arm. REVLIMID is not indicated and not recommended
for use in CLL outside of controlled clinical trials.
5.6 Second Primary Malignancies
Patients with multiple myeloma treated with lenalidomide in studies including
melphalan and stem cell transplantation had a higher incidence of second
primary malignancies, particularly acute myelogenous leukemia (AML) and
Hodgkin lymphoma, compared to patients in the control arms who received
similar therapy but did not receive lenalidomide. Monitor patients for the
development of second malignancies. Take into account both the potential
benefit of lenalidomide and the risk of second primary malignancies when
considering treatment with lenalidomide.
5.7 Hepatotoxicity
Hepatic failure, including fatal cases, has occurred in patients treated with
lenalidomide in combination with dexamethasone. In clinical trials, 15% of
patients experienced hepatotoxicity (with hepatocellular, cholestatic and
mixed characteristics); 2% of patients with multiple myeloma and 1% of
patients with myelodysplasia had serious hepatotoxicity events. The
mechanism of drug-induced hepatotoxicity is unknown. Pre-existing
viral liver disease, elevated baseline liver enzymes, and concomitant
medications may be risk factors. Monitor liver enzymes periodically. Stop
REVLIMID upon elevation of liver en