CLINICAL NEWS
“Extended platelet survival leads to
platelet exhaustion, with reduced
ability to mobilize granular release.”
—IRINA PLEINES, PhD
Hall Institute of Medical Research in Parkville,
Australia, and co-authors explained. “However,
the function of these long-lived platelets has not
been investigated.”
To examine the functional outcomes of
extending platelet survival, the researchers first
washed platelets from mice with a constitutive
deletion of Bak and a platelet-specific deletion
of Bax, confirming the hypothesis that removing Bak and Bax leaves platelets fully resistant
T:7”
Table 6: Grade 3/4 Adverse Reactions Reported in ≥2% Patients
and With a ≥1% Difference in Proportion of Patients Between the
REVLIMID/dexamethasone and Placebo/dexamethasone groups
System Organ Class/ Preferred Term REVLIMID/Dex# Placebo/Dex#
(N=353)
(N=350)
n (%)
n (%)
Eye Disorders
Cataract
6 (1.7)
1 (0.3)
Cataract Unilateral
5 (1.4)
0 (0.0)
Psychiatric Disorder
Depression
10 (2.8)
6 (1.7)
Venous and Arterial Thromboembolism [see Boxed Warning, Warnings
and Precautions (5.4)]
Deep vein thrombosis (DVT) was reported as a serious (7.4%) or severe
(8.2%) adverse drug reaction at a higher rate in the REVLIMID/dexamethasone
group compared to 3.1 % and 3.4% in the placebo/dexamethasone group,
respectively in the 2 studies in patients with at least 1 prior therapy with
discontinuations due to DVT adverse reactions reported at comparable rates
between groups. In the NDMM study, DVT was reported as an adverse
reaction (all grades: 10.3%, 7.2%, 4.1%), as a serious adverse reaction
(3.6%, 2.0%, 1.7%), and as a Grade 3/4 adverse reaction (5.6%, 3.7%,
2.8%) in the Rd Continuous, Rd18, and MPT Arms, respectively.
Discontinuations and dose reductions due to DVT adverse reactions were
reported at comparable rates between the Rd Continuous and Rd18 Arms
(both <1%). Interruption of REVLIMID treatment due to DVT adverse
reactions was reported at comparable rates between the Rd Continuous
(2.3%) and Rd18 (1.5%) arms.
Pulmonary embolism (PE) was reported as a serious adverse drug reaction
(3.7%) or Grade 3/4 (4.0%) at a higher rate in the REVLIMID/dexamethasone
group compared to 0.9% (serious or grade 3/4) in the placebo/dexamethasone
group in the 2 studies in patients with, at least 1 prior therapy, with
discontinuations due to PE adverse reactions reported at comparable rates
between groups. In the NDMM study, the frequency of adverse reactions of
PE was similar between the Rd Continuous, Rd18, and MPT Arms for
adverse reactions (all grades: 3.9%, 3.3%, and 4.3%, respectively), serious
Myocardial infarction was reported as a serious (1.7%) or severe (1.7%)
adverse drug reaction at a higher rate in the REVLIMID/dexamethasone
group compared to 0.6 % and 0.6% respectively in the placebo/
dexamethasone group. Discontinuation due to MI (including acute) adverse
reactions was 0.8% in REVLIMID/dexamethasone group and none in the
placebo/dexamethasone group. In the NDMM study, myocardial infarction
(including acute) was reported as an adverse reaction (all grades: 2.4%,
0.6%, and 1.1%), as a serious adverse reaction, (2.3%, 0.6%, and
1.1%), or as a severe adverse reaction (1.9%, 0.6%, and 0.9%) in the
Rd Continuous, Rd18, and MPT Arms, respectively.
Stroke (CVA) was reported as a serious (2.3%) or severe (2.0%) adverse drug
reaction in the REVLIMID/dexamethasone group compared to 0.9% and
0.9% respectively in the placebo/dexamethasone group. Discontinuation
due to stroke (CVA) was 1.4% in REVLIMID/dexamethasone group and
0.3% in the placebo/dexamethasone group. In the NDMM study, CVA was
reported as an adverse reaction (all grades: 0.8%, 0.6%, and 0.6%), as a
serious adverse reaction (0.8%, 0.6 %, and 0.6%), or as a severe adverse
reaction (0.6%, 0.6%, 0.2%) in the Rd Continuous, Rd18, and MPT arms
respectively.
Other Adverse Reactions: After At Least One Prior Therapy for MM
In these 2 studies, the following adverse drug reactions (ADRs) not
described above that occurred at ≥1% rate and of at least twice of the
placebo percentage rate were reported:
Blood and lymphatic system disorders: pancytopenia, autoimmune
hemolytic anemia
Cardiac disorders: bradycardia, myocardial infarction, angina pectoris
Endocrine disorders: hirsutism
Eye disorders: blindness, ocular hypertension
Gastrointestinal disorders: gastrointestinal hemorrhage, glossodynia
General disorders and administration site conditions: malaise
Investigations: liver function tests abnormal, alanine aminotransferase
increased
Nervous system disorders: cerebral ischemia
Psychiatric disorders: mood swings, hallucination, loss of libido
Reproductive system and breast disorders: erectile dysfunction
Respiratory, thoracic and mediastinal disorders: cough, hoarseness
Skin and subcutaneous tissue disorders: exanthem, skin
hyperpigmentation
6.2 Postmarketing Experience
The following adverse drug reactions have been identified from the
worldwide post-marketing experience with REVLIMID: Allergic conditions
(angioedema, SJS, TEN), tumor lysis syndrome (TLS) and tumor flare
reaction (TFR), pneumonitis, hepatic failure, including fatality, toxic
hepatitis, cytolytic hepatitis, cholestatic hepatitis, and mixed cytolytic/
cholestatic hepatitis and transient abnormal liver laboratory tests. Because
these reactions are reported voluntarily from a population of uncertain
size, it is not always possible to reliably estimate their frequency or
establish a causal relationship to drug exposure [see Warnings and
Precautions Section (5.7 to 5.10)].
Cases of hypothyroidism and hyperthyroidism have also been reported.
Optimal control of thyroid function is recommended before start of
treatment. Baseline and ongoing monitoring of thyroid function is
recommended.
7 DRUG INTERACTIONS
Results from human in vitro studies show that REVLIMID is neither
metabolized by nor