CLINICAL NEWS
ate, and low-risk based on only a few markers.”
The impact of genomic risk factors on patient
outcomes can sometimes be difficult to determine, particularly in the setting of co-occurring
genomic lesions. The tool developed and tested
by the researchers recognizes mutations in 55
prognostically relevant genes along with 18 of the
most common cytogenic legions. It also takes into
account blood counts, patient age, and gender.
The authors used detailed diagnostic, treat-
• CEBPA-/-
ment, and survival data gathered from 1,540 patients with AML who were enrolled in three trials
from the German-Austrian AML Study Group.
Through systematic evaluation of riskmodeling strategies, the researchers identified
factors associated either positively or negatively
with mortality, using a combination of “many
small and few large” variables, including:
• FLT3ITD
• TP53
• Fusion genes generated by t(15;17),
inv(16), and inv(3) rearrangements
• NPM1
• Complex karyotype
T:7”
4.2 Allergic Reactions
REVLIMID is contraindicated in patients who have demonstrated
hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic
epidermal necrolysis) to lenalidomide [see Warnings and Precautions
(5.8)].
5.2 REVLIMID REMS™ Program
Because of the embryo-fetal risk [see Warnings and Precautions (5.1)],
REVLIMID is available only through a restricted program under a Risk
Evaluation and Mitigation Strategy (REMS), the REVLIMID REMS™
program (formerly known as the “RevAssist®” program).
Required components of the REVLIMID REMS™ program include the
following:
• Prescribers must be certified with the REVLIMID REMS™ program by
enrolling and complying with the REMS requirements.
• Patients must sign a Patient-Physician agreement form and comply
with the REMS requirements. In particular, female patients of
reproductive potential who are not pregnant must comply with the
pregnancy testing and contraception requirements [see Use in Specific
Populations (8.6)] and males must comply with contraception
requirements [see Use in Specific Populations (8.6)].
• Pharmacies must be certified with the REVLIMID REMS™ program,
must only dispense to patients who are authorized to receive REVLIMID
and comply with REMS requirements.
Further information about the REVLIMID REMS™ program is available at
www.celgeneriskmanagement.com or by telephone at 1-888-423-5436.
5.3 Hematologic Toxicity
REVLIMID can cause significant neutropenia and thrombocytopenia.
Monitor patients with neutropenia for signs of infection. Advise patients to
observe for bleeding or bruising, especially with use of concomitant
medication that may increase risk of bleeding. Patients taking REVLIMID
should have their complete blood counts assessed periodically as
described below [see Dosage and Administration (2.1, 2.2, 2.3)].
Patients taking REVLIMID in combination with dexamethasone for MM
should have their complete blood counts (CBC) assessed every 7 days
(weekly) for the first 2 cycles, on Days 1 and 15 of Cycle 3, and every
Patients taking REVLIMID for MDS should have their complete blood counts
monitored weekly for the first 8 weeks and at least monthly thereafter.
Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled
in the MDS study. In the 48% of patients who developed Grade 3 or 4
neutropenia, the median time to onset was 42 days (range, 14-411 days),
and the median time to documented recovery was 17 days (range, 2-170 days).
In the 54% of patients who developed Grade 3 or 4 thrombocytopenia, the
median time to onset was 28 days (range, 8-290 days), and the median
time to documented recovery was 22 days (range, 5-224 days) [see
Boxed Warning and Dosage and Administration (2.2)].
Patients taking REVLIMID for MCL should have their complete blood
counts monitored weekly for the first cycle (28 days), every 2 weeks during
cycles 2-4, and then monthly thereafter. Patients may require dose
interruption and/or dose reduction. 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 after at least one prior therapy
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. In the
newly diagnosed multiple myeloma (NDMM) study in which nearly all
patients received antithrombotic prophylaxis, DVT was reported as a
serious adverse reaction (3.6%, 2.0%, and 1.7%) in the Rd Continuous,
Rd18, and MPT Arms, respectively. The frequency of serious adverse
reactions of PE was similar between the Rd Conti