On Location 2015 ASH Annual Meeting
New Framework Combines Genomic and Clinical Data
to Predict Outcomes for Patients with AML
Using both genomic and clinical data, researchers have developed a new prognostic framework
to predict outcomes, including mortality, in
patients with acute myeloid leukemia (AML),
according to a recent study conducted by Moritz
Gerstung, PhD, and colleagues from the European Bioinformatics Institute EMBL-EBI and
Wellcome Trust Sanger Institute in Cambridge,
United Kingdom. Dr. Gertsung presented the
results at the 2015 ASH Annual Meeting.
“Our approach is the first attempt to predict
outcomes based on a comprehensive set of
prognostic variables,” Dr. Gerstung said, “unlike
previous approaches that force patients into a
small set of categories, such as high, intermedi-
T:7”
REVLIMID [lenalidomide] capsules, for oral use
Table 1: Dose Adjustments for Hematologic Toxicities for MM
The following is a Brief Summary; refer to full Prescribing Information for
complete product information.
Platelet counts
WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and
VENOUS and ARTERIAL THROMBOEMBOLISM
Embryo-Fetal Toxicity
Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide
analogue, caused limb abnormalities in a developmental monkey study.
Thalidomide is a known human teratogen that causes severe lifethreatening human birth defects. If lenalidomide is used during pregnancy,
it may cause birth defects or embryo-fetal death. In females of reproductive
potent ial, obtain 2 negative pregnancy tests before starting REVLIMID®
treatment. Females of reproductive potential must use 2 forms of
contraception or continuously abstain from heterosexual sex during and
for 4 weeks after REVLIMID treatment [see Warnings and Precautions
(5.1), and Medication Guide (17)]. To avoid embryo-fetal exposure to
lenalidomide, REVLIMID is only available through a restricted
distribution program, the REVLIMID REMS™ program (formerly known
as the “RevAssist®” program) (5.2).
Information about the REVLIMID REMS™ program is available at
www.celgeneriskmanagement.com or by calling the manufacturer’s
toll-free number 1-888-423-5436.
Hematologic Toxicity (Neutropenia and Thrombocytopenia)
REVLIMID can cause significant neutropenia and thrombocytopenia.
Eighty percent of patients with del 5q myelodysplastic syndromes had to
have a dose delay/reduction during the major study. Thirty-four percent
of patients had to have a second dose delay/reduction. Grade 3 or 4
hematologic toxicity was seen in 80% of patients enrolled in the study.
Patients on therapy for del 5q myelodysplastic syndromes should have
their complete blood counts monitored weekly for the first 8 weeks of
therapy and at least monthly thereafter. Patients may require dose
interruption and/or reduction. Patients may require use of blood product
support and/or growth factors [see Dosage and Administration (2.2)].
1 INDICATIONS AND USAGE
1.1 Multiple Myeloma
REVLIMID in combination with dexamethasone is indicated for the
treatment of patients with multiple myeloma (MM).
1.4 Limitations of Use:
REVLIMID is not indicated and is not recommended for the treatment of
patients with CLL outside of controlled clinical trials [see Warnings and
Precautions (5.5)].
2 DOSAGE AND ADMINISTRATION
REVLIMID should be taken orally at about the same time each day, either
with or without food. REVLIMID capsules should be swallowed whole
with water. The capsules should not be opened, broken, or chewed.
2.1 Multiple Myeloma
Multiple Myeloma
The recommended starting dose of REVLIMID is 25 mg orally once daily
on Days 1-21 of repeated 28-day cycles in combination with dexamethasone.
Refer to Section 14.1 for specific dexamethasone dosing. For patients
> 75 years old, the starting dose of dexamethasone may be reduced.
Treatment should be continued until disease progression or unacceptable
toxicity.
In patients who are not eligible for autologous stem cell transplantation
(ASCT), treatment should continue until disease progression or unacceptable
toxicity. For patients who are ASCT-eligible, hematopoietic stem cell
mobilization should occur within 4 cycles of a REVLIMID-containing
therapy [see Warnings and Precautions (5.11)].
Dose Adjustments for Hematologic Toxicities During Multiple Myeloma
Treatment
Dose modification guidelines, as summarized in Table 1 below, are
recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia
or other Grade 3 or 4 toxicity judged to be related to REVLIMID.
When Platelets
Recommended Course
Fall to <30,000/mcL
Interrupt REVLIMID treatment, follow
CBC weekly
Resume REVLIMID at next lower dose.
Do not dose below 2.5 mg daily
Return to ≥30,000/mcL
For each subsequent drop
<30,000/mcL
Return to ≥30,000/mcL
Interrupt REVLIMID treatment
Resume REVLIMID at next lower dose.
Do not dose below 2.5 mg daily
Absolute Neutrophil counts (ANC)
Neutropenia in MM
When Neutrophils
Recommended Course
Fall to <1000/mcL
Return to ≥1,000/mcL and
neutropenia is the only toxicity
Interrupt REVLIMID treatment, follow
CBC weekly
Resume REVLIMID at 25 mg daily or
initial starting dose
Return to ≥1,000/mcL and if
other toxicity
Resume REVLIMID at next lower dose.
Do not dose below 2.5 mg daily
For each subsequent drop
<1,000/mcL
Return to ≥1,000/mcL
Interrupt REVLIMID treatment
Resume REVLIMID at next lower dose.
Do not dose below 2.5 mg daily
Other Toxicities in MM
For other Grade 3/4 toxicities judged to be related to REVLIMID, hold
treatment and restart at the physician’s discretion at next lower dose level
when toxicity has resolved to ≤ Grade 2.
Starting Dose Adjustment for Renal Impairment in MM:
[See Dosage and Administration (2.4)].
2.4 Starting Dose for Renal Impairment in MM
Since REVLIMID is primarily excreted unchanged by the kidney, adjustments
to the starting dose of REVLIMID are recommended to provide appropriate
drug exposure in patients with moderate or severe renal impairment and
in patients on dialysis. Based on a pharmacokinetic study in patients with
renal impairment due to non-malignant conditions, REVLIMID starting
dose adjustment is recommended for patients with CLcr < 60 mL/min.
The recommendations for initial starting doses for patients with MM are
as follows:
Table 3: Starting Dose Adjustments for Patients with
Renal Impairment in MM
Category
Renal Function
(Cockcroft-Gault)
Dose in MM
Moderate Renal
Impairment
CLcr 30-50 mL/min
10 mg
Every 24 hours
Severe Renal
Impairment
CLcr < 30 mL/min
(not requiring dialysis)
15 mg
Every 48 hours
End Stage
Renal Disease
CLcr < 30 mL/min
(requiring dialysis)
5 mg
Once daily. On dialysis days,
administer the dose following
dialysis.
Moderate renal impairment for MM: Consider escalating the dose to 15 mg
after 2 cycles if the patient tolerates the 10 mg dose of lenalidomide
without dose-limiting toxicity.
After initiation of REVLIMID therapy, subsequent REVLIMID dose increase
or decrease is based on individual patient treatment tolerance, as
described elsewhere [See Dosage and Administration (2.1-2.3)].
4 CONTRAINDICATIONS
4.1 Pregnancy
REVLIMID can cause fetal harm when administered to a pregnant female.
Limb abnormalities were seen in the offspring of monkeys that were
dosed with lenalidomide during organogenesis. This effect was seen at all
doses tested. Due to the results of this developmental monkey study, and
lenalidomide’s structural similarities to thalidomide, a known human
teratogen, lenalidomide is contraindicated in females who are pregnant
[see Boxed Warning]. If this drug is used during pregnancy or if the
patient becomes pregnant while t aking this drug, the patient should
be apprised of the potential hazard to the fetus [see Warnings and
Precautions (5.1, 5.2), Use in Special Populations (8.1), (8.6)].
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Venous and Arterial Thromboembolism
REVLIMID has demonstrated a significantly increased risk of deep vein
thrombosis (DVT) and pulmonary embolism (PE), as well as risk of
myocardial infarction and stroke in patients with multiple myeloma who
were treated with REVLIMID and dexamethasone therapy. Monitor for
and advise patients about signs and symptoms of thromboembolism.
Advise patients to seek immediate medical care if they develop symptoms
such as shortness of breath, chest pain, or arm or leg swelling.
Thromboprophylaxis is recommended and the choice of regimen should
be based on an assessment of the patient’s underlying risks [see
Warnings and Precautions (5.4)].
Thrombocytopenia in MM