CLINICAL NEWS
thawed, washed, and infused on the
first day of treatment. A second unit
was treated ex vivo for 30 minutes
with the enzyme fucosyltransferase-VI
(FTVI) and guanosine diphosphate
fucose to enhance the interaction of
CD34+ stem and early progenitor
cells with microvessels. Results from
these 22 patients were compared with
results from 31 historical controls who
had undergone double unmanipulated
CBT at the same center.
FTVI treatment led to maximal
fucosylation of CD34+ cells: Expression
was only 36.5 percent (95% CI 31.541.5%) before FTVI treatment, but it
increased to 98.9 percent (95% CI 98.299.6%) post-treatment. “FTVI treatment
also led to substantial fucosylation
of CD61+ megakaryocytes, CD14+
monocytes, and CD56+CD3- NK cells,”
the authors wrote, “while CD3+ T cells
and CD19+ B cells were not fucosylated
at all following this treatment.”
All cord blood cell infusions were
well tolerated, with no serious infusionrelated toxicity during a median
follow-up of 8 months, the researchers
reported. Incidence of graft-versus-host
disease (GVHD) at 100 days were not
significantly different between groups:
• Acute grade II-IV: 40.91 percent
(95% CI 20.18-60.71%) in the study
group versus 38.71 percent (95%
CI 21.67-55.49%) in controls
T:7”
Males
Lenalidomide is present in the semen of males who take REVLIMID.
Therefore, males must always use a latex or synthetic condom during any
sexual contact with females of reproductive potential while taking
REVLIMID, during dose interruptions and for up to 28 days after
discontinuing REVLIMID, even if they have undergone a successful
vasectomy. Male patients taking REVLIMID must not donate sperm
8.7 Renal Impairment
Since lenalidomide 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 (CLcr
30-60 mL/min) or severe renal impairment (CLcr < 30 mL/min) and in
patients on dialysis [see Dosage and Administration (2.4)].
8.8 Hepatic Impairment
No dedicated study has been conducted in patients with hepatic impairment.
The elimination of unchanged lenalidomide is predominantly by the renal
route.
10 OVERDOSAGE
There is no specific experience in the management of lenalidomide
overdose in patients with MM, MDS, or MCL. In dose-ranging studies in
healthy subjects, some were exposed to up to 200 mg (administered
100 mg BID) and in single-dose studies, some subjects were exposed to
up to 400 mg. Pruritus, urticaria, rash, and elevated liver transaminases
were the primary reported AEs. In clinical trials, the dose-limiting toxicity
was neutropenia and thrombocytopenia.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies with lenalidomide have not been conducted.
Lenalidomide was not mutagenic in the bacterial reverse mutation assay
(Ames test) and did not induce chromosome aberrations in cultured
human peripheral blood lymphocytes, or mutations at the thymidine
kinase (tk) locus of mouse lymphoma L5178Y cells. Lenalidomide did not
increase morphological transformation in Syrian Hamster Embryo assay
or induce micronuclei in the polychromatic erythrocytes of the bone
marrow of male rats.
17 PATIENT COUNSELING INFORMATION
See FDA-approved Patient labeling (Medication Guide)
Embryo-Fetal Toxicity
Advise patients that REVLIMID is contraindicated in pregnancy [see
Contraindications (4.1)]. REVLIMID is a thalidomide analog and can cause
serious birth defects or death to a developing baby [see Warnings and
Precautions (5.1) and Use in Specific Populations (8.1)].
• Advise females of reproductive potential that they must avoid pregnancy
while taking REVLIMID and for at least 4 weeks after completing therapy.
• Initiate REVLIMID treatment in females of reproductive potential only
following a negative pregnancy test.
• Advise females of reproductive potential of the importance of monthly
pregnancy tests and the need to use two different forms of contraception
including at least one highly effective form simultaneously during
REVLIMID therapy, during dose interruption and for 4 weeks after she
has completely finished taking REVLIMID. Highly effective forms of
contraception other than tubal ligation include IUD and hormonal (birth
control pills, injections, patch or implants) and a partner’s vasectomy.
Additional effective contraceptive methods include latex or synthetic
condom, diaphragm and cervical cap.
• Instruct patient to immediately stop taking REVLIMID and contact her
doctor if she becomes pregnant while taking this drug, if she misses her
menstrual period, or experiences unusual menstrual