CLINICAL NEWS
On Location 2018 ASH Annual Meeting
Continued from page 19
six-cycle group.
Reducing the number of CHOP cycles also
reduced the number of adverse events by approxi-
mately one-third ( TABLE 1 ). “We observed only two
therapy-related deaths in the six-cycle arm and
none in the four-cycle arm,” Dr. Poeschel said.
While these results demonstrate that four
cycles of CHOP are noninferior to six cycles, Dr.
Poeschel noted that the findings are not gener-
alizable to the larger population of patients with
higher-risk DBLCL or patients outside of the
well-defined subgroup enrolled in this study.
The authors report financial relationships with
Roche, Novartis, Amgen, and Bristol-Myers Squibb.
REFERENCE
Poeschel V, Held G, Ziepert M, et al. Excellent outcome of young patients (18-60
years) with favourable-prognosis diffuse large B-cell lymphoma (DLBCL) treated
with 4 cycles CHOP plus 6 applications of rituximab: results of the 592 patients
of the FLYER trial of the DSHNHL/GLA. Abstract #781. Presented at the 2018 ASH
Annual Meeting, December 3, 2018; San Diego, CA.
TABLE 1.
Adverse Events
6 Cycles R-CHOP
(n=295)
Any-grade Grade 3/4
Leukocytopenia 237 Anemia 172
Thrombocytopenia
Non-hematologic adverse events
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
1 INDICATIONS AND USAGE
1.1 Multiple Myeloma
REVLIMID in combination with dexamethasone is indicated for the
treatment of patients with multiple myeloma (MM).
REVLIMID is indicated as maintenance therapy in patients with MM
following autologous hematopoietic stem cell transplantation
(auto-HSCT).
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
REVLIMID Combination Therapy
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 (5.12)].
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.
Cosmos Communications
Thrombocytopenia in MM
When Platelets Recommended Course
Days 1-21 of repeated 28-day cycle
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
Days 1-21 of repeated 28-day cycle
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
REVLIMID Maintenance Therapy Following Auto-HSCT
Following auto-HSCT, initiate REVLIMID maintenance therapy after
adequate hematologic recovery (ANC ≥ 1000/mcL and/or platelet counts
≥75,000/mcL). The recommended starting dose of REVLIMID is 10 mg
once daily continuously (Days 1-28 of repeated 28-day cycles) until
disease progression or unacceptable toxicity. After 3 cycles of maintenance
therapy, the dose can be increased to 15 mg once daily if tolerated.
Dose Adjustments for Hematologic Toxicities During MM Treatment
Dose modification guidelines, as summarized in Table 2 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.
Table 2: Dose Adjustments for Hematologic Toxicities for MM
Platelet counts
Thrombocytopenia in MM
When Platelets Recommended Course
Fall to <30,000/mcL Return to ≥30,000/mcL Interrupt REVLIMID treatment, follow
CBC weekly
Resume REVLIMID at next lower dose,
continuously for Days 1-28 of
repeated 28-day cycle
If at the 5 mg daily dose,
For a subsequent drop
<30,000/mcL Interrupt REVLIMID treatment. Do not
dose below 5 mg daily for Day 1 to 21
of 28 day cycle
Return to ≥30,000/mcL Resume REVLIMID at 5 mg daily for
Days 1 to 21of 28-day cycle. Do not
dose below 5 mg daily for Day 1 to 21
of 28 day cycle
Absolute Neutrophil counts (ANC)
Neutropenia in MM
When Neutrophils Recommended Course
Fall to <500/mcL Interrupt REVLIMID treatment, follow
CBC weekly
Resume REVLIMID at next lower dose,
continuously for Days 1-28 of repeated
28-day cycle
Return to ≥500/mcL
If at 5 mg daily dose,
For a subsequent drop <500/mcL Interrupt REVLIMID treatment. Do not
dose below 5 mg daily for Days 1 to
21 of 28-day cycle
Return to >500/mcL Resume REVLIMID at 5 mg daily for
Days 1 to 21 of 28-day cycle. Do not
dose below 5 mg daily for Days 1 to
21 of 28-day cycle
1
Q1
Q2
Any-grade Grade 3/4
110 171 80
8 107 2
Hematologic adverse events
REVLIMID [lenalidomide] capsules, for oral use
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 life-
threatening 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)]. To avoid embryo-fetal exposure to lenalidomide,
REVLIMID is only available through a restricted distribution program,
the REVLIMID REMS ® 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 (2.1)].
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)].
4 Cycles R-CHOP
(n=293)
17 7 16 5
1,295 70 835 46