Written in Blood
Continued from page 45
myeloid leukemia, acute lymphocytic
leukemia, chronic myeloid leukemia, and
myelodysplastic syndromes.
The researchers analyzed two independent data sets:
• A training cohort for transplant from
1988 to 2006 (n=6,349)
• A validation cohort for transplant
from 2007 to 2011 (n=4,690)
Characteristics of the training cohort are
seen in TABLE 2, page 45. In the 1988 to
2006 cohort, the median age of donors
was 35 years (range, 18-61 years), and
male donors accounted for 62 percent of
transplantations. Fifty-nine percent of
donor–recipient pairs were 8/8 HLA-
characteristics were similar to the original
cohort.
Dr. Kollman and investigators analyzed
the following donor-related variables:
matched and 43 percent were ABO
blood–matched. Notably, older donors
were more likely to be mismatched to
their recipients, be cytomegalovirusseropositive, and donate grafts with lower
cell dose compared with younger donors
(p<0.001 for all).
In the 2007 to 2011 cohort, most of
the donors (55%) were 18 to 32 years of
age. Overall, patient, disease, and donor
• Donor age: 18-32 years vs. 33-50 years
vs. ≥50 years
• Donor–recipient sex match
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
potential, 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
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