Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ:
CELG) announced results from a retrospective analysis to assess the risk
of acute myeloid leukemia (AML) progression and death in REVLIMID
(lenalidomide)-treated versus untreated patients with red blood cell
(RBC) transfusion-dependent patients with IPSS Low or Int-1 risk
myelodysplastic syndromes (MDS) with deletion 5q chromosome (with or
without additional cytogenetic abnormalities). These results were
presented during the 53rd Annual Meeting of the American
Society of Hematology in San Diego, CA.
In this retrospective analysis, 295 lenalidomide-treated patients from
two Celgene-sponsored multicenter trials, MDS-003 and MDS-004, were
compared with 125 untreated patients from an international multi-center
MDS Registry with similar baseline characteristics who had received best
supportive care only, including erythropoiesis-stimulating agents (ESAs)
in some patients. Baseline characteristics of lenalidomide-treated
patients were similar to registry patients, except for a higher RBC
transfusion burden among lenalidomide-treated patients (median [range]
units/8 weeks: 6 [1-25] vs. 2 [1-10]).
The lenalidomide-treated patients benefited from a reduction in risk of
death, while no risk of progression to AML was observed, despite a
higher transfusion burden at baseline compared with patients from the
MDS registry who had not received lenalidomide.
The two- and five-year cumulative overall survival (OS) probabilities
were 90% and 54% for patients treated with lenalidomide compared with
74% and 41% for patients not treated with lenalidomide. In addition, the
two- and five-year cumulative AML incidences were 7% and 23% for
patients treated with lenalidomide compared with 12% and 20% for
patients not treated with lenalidomide. The median OS was 5.2 years for
patients treated with lenalidomide compared with 3.8 years for patients
not treated with lenalidomide, and the median time to AML progression
had not been reached for either cohort.
Significant baseline factors associated with an increased risk of AML
progression included: complex cytogenetics (greater than or equal to 2,
p=0.002); 5–10% bone marrow blasts (p=0.016); and higher transfusion
burden (10% increase in risk per unit at baseline, p=0.029).
Furthermore, higher hemoglobin (Hgb) levels at baseline were associated
with a reduced risk of AML progression (p=0.054). Factors that reduced
the risk of death included treatment with lenalidomide (p=0.012); higher
baseline Hgb levels (p=0.028); higher baseline platelet counts
(p=0.035), and female gender (p=0.002). The risk of death increased as a
result of baseline transfusion burden (p=0.037) and age (p<0.001).
REVLIMID is approved in combination with dexamethasone for the treatment
of patients with multiple myeloma who have received at least one prior
therapy in nearly 70 countries, encompassing Europe, the Americas, the
Middle-East and Asia, and in combination with dexamethasone for the
treatment of patients whose disease has progressed after one therapy in
Australia and New Zealand.
REVLIMID is also approved in the United States, Canada, Switzerland,
Australia, New Zealand, and several Latin American countries, as well as
Malaysia and Israel, for transfusion-dependent anaemia due to low- or
intermediate-1-risk MDS associated with a deletion 5q cytogenetic
abnormality with or without additional cytogenetic abnormalities.
Marketing Authorization Applications are currently being evaluated in a
number of other countries.
Since 1998, Celgene continues to be a pioneer in creating environments
in which patients can benefit from our disease-altering therapies
safely. As a result, hundreds of thousands of patients worldwide have
accessed the clinical benefits of our therapies through our
performance-based risk management programs including, S.T.E.P.S.®,
RevAssist® and RevMate®, which form the foundation
of our commitment to patient safety.
U.S. Regulatory Information for REVLIMID
REVLIMID® (lenalidomide) in combination with
dexamethasone is indicated for the treatment of multiple myeloma (MM)
patients who have received at least one prior therapy.
REVLIMID ® (lenalidomide) is indicated for patients with
transfusion-dependent anemia due to Low- or Intermediate-1–risk
myelodysplastic syndromes (MDS) associated with a deletion 5q
cytogenetic abnormality with or without additional cytogenetic
Important Safety Information
WARNING: FETAL RISK, HEMATOLOGIC TOXICITY, and
DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM
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 death to a developing baby. In
women of childbearing potential, obtain 2 negative pregnancy tests
before starting REVLIMID treatment. Women of childbearing potential must
use 2 forms of contraception or continuously abstain from heterosexual
sex during and for 4 weeks after REVLIMID treatment. To avoid fetal
exposure to lenalidomide, REVLIMID is only available in the United
States under a restricted distribution program called "RevAssist®."
Information about the RevAssist program is available at www.REVLIMID.com
or by calling the manufacturer's toll-free number 1-888-423-5436.
HEMATOLOGIC TOXICITY (NEUTROPENIA AND
REVLIMID can cause significant neutropenia and thrombocytopenia.
Eighty percent of patients with del 5q MDS 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 MDS 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
DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM
EXTEND BLACK BOX AROUND THIS PARAGRAPHREVLIMID has demonstrated a
significantly increased risk of deep vein thrombosis (DVT) and pulmonary
embolism (PE) in patients with MM who were treated with REVLIMID and