Nearly 70 abstracts, including more than 20
oral presentations highlight diverse portfolio of innovative
treatment modalities, including potentially transformative cell
therapies
Celgene Corporation (NASDAQ: CELG) today announced data from
nearly 70 Company-sponsored, global alliance and
investigator-initiated clinical studies evaluating Celgene’s
investigational and approved therapies will be presented at the
61st American Society of Hematology (ASH) Annual Meeting &
Exposition, December 7-10, in Orlando, Fla.
“Celgene has a deep and ongoing commitment to innovative
research and development in treatments for serious blood disorders,
with the potential to transform patient outcomes,” said Alise
Reicin, M.D., President, Global Clinical Development for Celgene.
“We look forward to ASH as an opportunity to highlight our
commitment and leadership in the research and development of novel
therapies for the treatment of blood cancers through new insights
in both CD19 and BCMA targeted cell therapies and important
progress in our myeloid pipeline.”
In leukemia and lymphoma, highlighted studies this year include
safety and efficacy results from the pivotal TRANSCEND NHL-001
study of an investigational CD-19 targeted chimeric antigen
receptor (CAR) T cell therapy lisocabtagene maraleucel (liso-cel)
in relapsed/refractory large B-cell non-Hodgkin lymphoma.
Additional liso-cel data from three ongoing studies will evaluate
the use of the therapy in an outpatient setting, as well as in
transplant noneligible patients with relapsed/refractory large
B-cell non-Hodgkin lymphoma (PILOT) and in patients with
relapsed/refractory chronic lymphocytic leukemia (TRANSCEND
CLL-004).
In multiple myeloma, other notable investigational cell therapy
abstracts include the first phase 1 clinical data from the
bi-specific T-Cell Engager (TCE) CC-93269 and updated phase 1
clinical data from CAR T program, bb21217, both targeting the
B-cell maturation antigen (BCMA) in relapsed/refractory
disease.
Several abstracts focusing on data in myeloid diseases including
longer-term response data from the phase 3 MEDALIST study of
luspatercept to treat anemia in patients with IPSS-R very low-,
low-, or intermediate-risk myelodysplastic syndromes with ring
sideroblasts who require red-blood-cell (RBC) transfusions will be
presented. Additionally, the first data from a phase 2 study of
luspatercept in myelofibrosis-associated anemia, results from a
study of fedratinib in myelofibrosis patients with low platelet
counts, and the first data from CELMoD agent CC-90009, a GSPT1
degrader in relapsed or refractory acute myeloid leukemia (AML)
will be presented.
Selected abstracts include*:
Lymphoma & Chronic Lymphocytic
Leukemia
- Abstract #66: Impact of Lisocabtagene Maraleucel (liso-cel)
Treatment on Health-related Quality of Life and Health Utility in
Patients (pts) with Relapsed/Refractory (R/R) Aggressive B-Cell
Non-Hodgkin Lymphoma (NHL): TRANSCEND NHL 001 (Oral
presentation; Saturday, December 7, 8:45 a.m., W308 Patrick)
- Abstract #202: Multiplexed Immunofluorescence (IF) Analysis
and Gene Expression Profiling of Biopsies from Patients with
Relapsed/Refractory (R/R) Diffuse Large B Cell Lymphoma (DLBCL)
Treated with Lisocabtagene Maraleucel (liso-cel) in TRANSCEND NHL
001 Reveal Patterns of Immune Infiltration Associated with Durable
Response (Oral presentation; Saturday, December 7, 12:45 p.m.,
Valencia A (W415A) Reiss)
- Abstract #241: Pivotal Safety and Efficacy Results from
TRANSCEND NHL 001, a Multicenter Phase 1 Study of Lisocabtagene
Maraleucel (liso-cel) in Relapsed/Refractory (R/R) Large B Cell
Lymphomas (Oral presentation; Saturday, December 7, 2:00 p.m.,
Hall E2, Abramson)
- Abstract #306: Interactome of Aiolos/Ikaros in Diffuse Large
B-Cell Lymphoma (DLBCL) Reveals Novel Combination of Cereblon
Modulators (CELMoD) and Histone Deacetylase (HDAC) Inhibitors
(Oral presentation; Saturday, December 7, 5:15 p.m., Valencia A
(W415A), Hagner)
- Abstract #347: Subgroup Analyses of Elderly Patients Aged ≥
70 Years in AUGMENT: A Phase III Randomized Study of Lenalidomide
Plus Rituximab (R2) vs Rituximab Plus Placebo (R-Placebo) in
Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin
Lymphoma (iNHL) (Oral presentation; Sunday, December 8, 8:30
a.m., Tangerine 3 (WF3-4), Trneny)
- Abstract #503: Rapid Undetectable MRD (uMRD) Responses in
Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic
Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Treated with
liso-cel, a CD19-directed CAR T Cell Product: Updated Results from
TRANSCEND CLL 004, a Phase 1/2 Study Including Patients with
High-Risk Disease Previously Treated with Ibrutinib (Oral
presentation; Sunday, December 8, 5:30 p.m., Hall D, Siddiqi)
- Abstract #2868: Outpatient Treatment of Lisocabtagene
Maraleucel (liso-cel) in Three Ongoing Clinical Studies in
Relapsed/Refractory B-cell Non-Hodgkin Lymphoma (NHL), Including
Transplant Noneligible Patients: TRANSCEND NHL 001, OUTREACH, and
PILOT (Poster presentation; Sunday, December 8, 6:00 p.m., Hall
B, Bachier)
- Abstract #2882: Lisocabtagene Maraleucel (liso-cel) for
Treatment of Transplant-Ineligible Patients with
Relapsed/Refractory (R/R) Aggressive Non-Hodgkin Lymphoma (NHL):
Initial Results from the PILOT Study (Poster presentation;
Sunday, December 8, 6:00 p.m., Hall B, Sehgal)
- Abstract #591: Statistical Learning Approaches for
Predicting Lisocabtagene Maraleucel (Liso-Cel; JCAR017) Drug
Product Composition from Donor-Selected Material Composition
(Oral presentation; Monday, December 9, 7:30 a.m., W414AB,
Jiang)
- Abstract #593: Lisocabtagene Maraleucel (liso-cel; JCAR017)
Manufacturing Process Control and Robustness Across CD19+
Hematological Malignancies (Oral presentation; Monday, December
9, 8:00 a.m., W414AB, Teoh)
- Abstract #923: Clustering of Transcriptomic Signatures in
Newly Diagnosed Diffuse Large B-Cell Lymphoma Identifies Two
High-Risk Subgroups Which Increase in Prevalence at Relapse
(Oral presentation; Monday, December 9, 7:15 p.m., W414AB,
Ortiz)
Multiple Myeloma
- Abstract #143: First Clinical Study of the B-Cell Maturation
Antigen (BCMA) 2+1 T-Cell Engager (TCE) CC-93269 in Patients (Pts)
with Relapsed/Refractory Multiple Myeloma (RRMM): Interim Results
of a Phase 1 Multicenter Trial(Oral presentation; Saturday,
December 7, 10:30 a.m., Hall E1, Costa)
- Abstract #1812: CC-92480 is a Novel CRBN E3 Ligase
Modulating Drug (CELMoD) that Shows Enhanced Tumoricidal and
Immunomodulatory Activity Against Sensitive and Resistant Multiple
Myeloma Cells (Poster presentation; Saturday, December 7, 5:30
p.m., Hall B, Lopez-Girona)
- Abstract #1815: CC-92480, a New Generation
Cereblon-modulating Agent, is Highly Synergistic in Combination
with Standard Care Agents Dexamethasone, Bortezomib, and
Daratumamab in Multiple Myeloma (Poster presentation; Saturday,
December 7, 5:30 p.m., Hall B, Wong)
- Abstract #3119: Preclinical, Translational, and Clinical
Evidence of a Differentiated Profile for the Novel CELMoD,
Iberdomide (CC-220)(Poster presentation; Sunday, December 8,
6:00 p.m., Hall B, Lonial)
- Abstract #927: Updated Results from an Ongoing Phase 1
Clinical Study of bb21217 Anti-BCMA CAR T Therapy (Oral
presentation; Monday, December 9, 6:45 p.m., Valencia A (W415A),
Berdeja)
Myeloid Diseases
- Abstract #232: Clinical Activity of CC-90009, a Cereblon E3
Ligase Modulator and First-in-Class GSPT1 Degrader, as a Single
Agent in Patients with Relapsed or Refractory Acute Myeloid
Leukemia (R/R AML): First Results from a Phase I Dose-Finding
Study (Oral presentation; Saturday, December 7, 2:45 p.m.,
Chapin Theater (W320), Uy)
- Abstract #405: Elucidating the Mechanism of Action of
CC-90009, a Novel Cereblon E3 Ligase Modulator, in AML via
Genome-wide CRISPR Screen(Oral presentation; Sunday, December
8, 10:00 a.m., W414AB, Lu)
- Abstract #557: A Phase 2 Study of Luspatercept in Patients
with Myelofibrosis-Associated Anemia (Oral presentation;
Monday, December 9, 8:00 a.m., W304EFGH, Gerds)
- Abstract #643: Enasidenib Plus Azacitidine Significantly
Improves Complete Remission and Overall Response Compared with
Azacitidine Alone in Patients with Newly Diagnosed Acute Myeloid
Leukemia (AML) with Isocitrate Dehydrogenase 2 (IDH2) Mutations:
Interim Phase II Results from an Ongoing, Randomized Study
(Oral presentation; Monday, December 9, 10:30 a.m., Tangerine 3
(WF3-4), DiNardo)
- Abstract #841: Assessment of Longer-Term Efficacy and
Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled
MEDALIST Trial of Luspatercept to Treat Anemia in Patients (Pts)
with Revised International Prognostic Scoring System (IPSS-R) Very
Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS)
with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC)
Transfusions (Oral presentation; Monday, December 9, 4:30 p.m.,
W311ABCD, Fenaux)
- Abstract 668: Fedratinib Induces Spleen Responses and
Reduces Symptom Burden in Patients with Myeloproliferative Neoplasm
(MPN)-Associated Myelofibrosis (MF) and Low Platelet Counts, Who
were Either Ruxolitinib-Naïve or were Previously Treated with
Ruxolitinib (Oral presentation; Monday, December 9, 10:45 a.m.,
Room W311 EFGH, Harrison)
- Abstract #704 : Health-related Quality of Life (HRQoL) in
Patients with Myelofibrosis Treated with Fedratinib, an Oral,
Selective Inhibitor of Janus Kinase 2 (JAK2), in the Randomized,
Placebo-controlled, Phase III JAKARTA Study (Oral presentation;
Monday, December 9, 10:45 a.m., Valencia D (W415D), Mesa)
Beta thalassemia
- Abstract #3545: Evaluating Luspatercept Responders on
Number of Response Episodes, Duration of Clinical Benefit, and
Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled
BELIEVE Trial of Luspatercept in Adult Beta Thalassemia Patients
(Pts) Who Require Regular Red Blood Cell (RBC) Transfusions
(Poster presentation; Monday, December 9, 6 p.m., Hall B,
Viprakasit)
A complete listing of abstracts can be found at
https://www.hematology.org/Annual-Meeting/abstracts/
The safety and efficacy of investigational agents and/or
investigational uses of approved marketed products have not been
established. There is no guarantee that the agents will receive
health authority approval or become commercially available in any
country for the uses being investigated.
*All times Eastern Time
About REVLIMID®
REVLIMID® (lenalidomide) in combination with dexamethasone
(dex) is indicated for the treatment of adult patients with
multiple myeloma (MM)
REVLIMID is indicated as maintenance therapy in adult
patients with MM following autologous hematopoietic stem cell
transplantation (auto-HSCT)
REVLIMID is indicated for the treatment of adult 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
abnormalities
REVLIMID is indicated for the treatment of adult patients
with mantle cell lymphoma (MCL) whose disease has relapsed or
progressed after two prior therapies, one of which included
bortezomib
REVLIMID in combination with a rituximab product is indicated
for the treatment of adult patients with previously treated
follicular lymphoma (FL)
REVLIMID in combination with a rituximab product is indicated
for the treatment of adult patients with previously treated
marginal zone lymphoma (MZL)
REVLIMID is not indicated and is not recommended for the
treatment of patients with chronic lymphocytic leukemia (CLL)
outside of controlled clinical trials
REVLIMID is only available through a restricted distribution
program, REVLIMID REMS®.
Important Safety Information
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. To avoid embryo-fetal exposure to
lenalidomide, REVLIMID is only available through a restricted
distribution program, the REVLIMID REMS® program.
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 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.
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 MM 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.
CONTRAINDICATIONS
Pregnancy: REVLIMID can cause fetal harm when
administered to a pregnant female and is contraindicated in females
who are pregnant. If this drug is used during pregnancy or if the
patient becomes pregnant while taking this drug, the patient should
be apprised of the potential risk to the fetus
Severe Hypersensitivity Reactions: REVLIMID is
contraindicated in patients who have demonstrated severe
hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic
epidermal necrolysis) to lenalidomide
WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity: See Boxed WARNINGS
- Females of Reproductive Potential:
See Boxed WARNINGS
- Males: Lenalidomide is present in
the semen of patients receiving the drug. Males must always use a
latex or synthetic condom during any sexual contact with females of
reproductive potential while taking REVLIMID and for up to 4 weeks
after discontinuing REVLIMID, even if they have undergone a
successful vasectomy. Male patients taking REVLIMID must not donate
sperm
- Blood Donation: Patients must not
donate blood during treatment with REVLIMID and for 4 weeks
following discontinuation of the drug because the blood might be
given to a pregnant female patient whose fetus must not be exposed
to REVLIMID
REVLIMID REMS Program: See Boxed WARNINGS: Prescribers
and pharmacies must be certified with the REVLIMID REMS program by
enrolling and complying with the REMS requirements; pharmacies must
only dispense to patients who are authorized to receive REVLIMID.
Patients must sign a Patient-Physician Agreement Form and comply
with REMS requirements; female patients of reproductive potential
who are not pregnant must comply with the pregnancy testing and
contraception requirements and males must comply with contraception
requirements
Hematologic Toxicity: REVLIMID can cause significant
neutropenia and thrombocytopenia. Monitor patients with neutropenia
for signs of infection. Advise patients to observe for bleeding or
bruising, especially with use of concomitant medications that may
increase risk of bleeding. Patients may require dose interruption
and/or dose reduction. MM:
Monitor complete blood counts (CBC) in patients taking REVLIMID +
dexamethasone or REVLIMID as maintenance therapy, every 7 days for
the first 2 cycles, on days 1 and 15 of cycle 3, and every 28 days
thereafter. MDS: Monitor CBC in
patients on therapy for del 5q MDS, weekly for the first 8 weeks of
therapy and at least monthly thereafter. See Boxed WARNINGS
for further information. MCL:
Monitor CBC in patients taking REVLIMID for MCL weekly for the
first cycle (28 days), every 2 weeks during cycles 2-4, and then
monthly thereafter. FL/MZL:
Monitor CBC in patients taking REVLIMID for FL or MZL weekly for
the first 3 weeks of Cycle 1 (28 days), every 2 weeks during Cycles
2-4, and then monthly thereafter
Venous and Arterial Thromboembolism: See Boxed WARNINGS:
Venous thromboembolic events (DVT and PE) and arterial thromboses
(MI and CVA) are increased in patients treated with REVLIMID.
Patients with known risk factors, including prior thrombosis, may
be at greater risk and actions should be taken to try to minimize
all modifiable factors (e.g., hyperlipidemia, hypertension,
smoking). Thromboprophylaxis is recommended and the regimen should
be based on the patient’s underlying risks. ESAs and estrogens may
further increase the risk of thrombosis and their use should be
based on a benefit-risk decision
Increased Mortality in Patients With CLL: In a clinical
trial in the first-line treatment of patients with CLL,
single-agent REVLIMID therapy increased the risk of death as
compared to single-agent chlorambucil. Serious adverse
cardiovascular reactions, including atrial fibrillation, myocardial
infarction, and cardiac failure, occurred more frequently in the
REVLIMID arm. REVLIMID is not indicated and not recommended for use
in CLL outside of controlled clinical trials
Second Primary Malignancies (SPM): In clinical trials in
patients with MM receiving REVLIMID and in patients with FL or MZL
receiving REVLIMID + rituximab therapy, an increase of hematologic
plus solid tumor SPM, notably AML, have been observed. In MM
patients, MDS was also observed. Monitor patients for the
development of SPM. Take into account both the potential benefit of
REVLIMID and risk of SPM when considering treatment
Increased Mortality with Pembrolizumab: In clinical
trials in patients with MM, the addition of pembrolizumab to a
thalidomide analogue plus dexamethasone resulted in increased
mortality. Treatment of patients with MM with a PD-1-or PD-L1-
blocking antibody in combination with a thalidomide analogue plus
dexamethasone is not recommended outside of controlled clinical
trials
Hepatotoxicity: Hepatic failure, including fatal cases,
has occurred in patients treated with REVLIMID + dexamethasone.
Pre-existing viral liver disease, elevated baseline liver enzymes,
and concomitant medications may be risk factors. Monitor liver
enzymes periodically. Stop REVLIMID upon elevation of liver
enzymes. After return to baseline values, treatment at a lower dose
may be considered
Severe Cutaneous Reactions Including Hypersensitivity
Reactions: Angioedema and severe cutaneous reactions including
Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN),
and drug reaction with eosinophilia and systemic symptoms (DRESS)
have been reported. These events can be fatal. Patients with a
prior history of Grade 4 rash associated with thalidomide treatment
should not receive REVLIMID. REVLIMID interruption or
discontinuation should be considered for Grade 2-3 skin rash.
REVLIMID must be discontinued for angioedema, Grade 4 rash,
exfoliative or bullous rash, or if SJS, TEN, or DRESS is suspected
and should not be resumed following discontinuation for these
reactions
Tumor Lysis Syndrome (TLS): Fatal instances of TLS have
been reported during treatment with REVLIMID. The patients at risk
of TLS are those with high tumor burden prior to treatment. Closely
monitor patients at risk and take appropriate preventive
approaches
Tumor Flare Reaction (TFR): TFR has occurred during
investigational use of REVLIMID for CLL and lymphoma. Monitoring
and evaluation for TFR is recommended in patients with MCL, FL, or
MZL. Tumor flare may mimic the progression of disease (PD). In
patients with Grade 3 or 4 TFR, it is recommended to withhold
treatment with REVLIMID until TFR resolves to ≤Grade 1. REVLIMID
may be continued in patients with Grade 1 and 2 TFR without
interruption or modification, at the physician’s discretion
Impaired Stem Cell Mobilization: A decrease in the number
of CD34+ cells collected after treatment (>4 cycles) with
REVLIMID has been reported. Consider early referral to transplant
center to optimize timing of the stem cell collection
Thyroid Disorders: Both hypothyroidism and
hyperthyroidism have been reported. Measure thyroid function before
starting REVLIMID treatment and during therapy
Early Mortality in Patients With MCL: In another MCL
study, there was an increase in early deaths (within 20 weeks);
12.9% in the REVLIMID arm versus 7.1% in the control arm. Risk
factors for early deaths include high tumor burden, MIPI score at
diagnosis, and high WBC at baseline (≥10 x 109/L)
ADVERSE REACTIONS
Multiple Myeloma
- In newly diagnosed: The most frequently reported Grade 3
or 4 reactions included neutropenia, anemia, thrombocytopenia,
pneumonia, asthenia, fatigue, back pain, hypokalemia, rash,
cataract, lymphopenia, dyspnea, DVT, hyperglycemia, and leukopenia.
The highest frequency of infections occurred in Arm Rd Continuous
(75%) compared to Arm MPT (56%). There were more Grade 3 and 4 and
serious adverse reactions of infection in Arm Rd Continuous than
either Arm MPT or Rd18
- The most common adverse reactions reported in ≥20% (Arm Rd
Continuous): diarrhea (46%), anemia (44%), neutropenia (35%),
fatigue (33%), back pain (32%), asthenia (28%), insomnia (28%),
rash (26%), decreased appetite (23%), cough (23%), dyspnea (22%),
pyrexia (21%), abdominal pain (21%), muscle spasms (20%), and
thrombocytopenia (20%)
- Maintenance Therapy Post Auto-HSCT: The most frequently
reported Grade 3 or 4 reactions in ≥20% (REVLIMID arm) included
neutropenia, thrombocytopenia, and leukopenia. The serious adverse
reactions of lung infection and neutropenia (more than 4.5%)
occurred in the REVLIMID arm
- The most frequently reported adverse reactions in ≥20%
(REVLIMID arm) across both maintenance studies (Study 1, Study 2)
were neutropenia (79%, 61%), thrombocytopenia (72%, 24%),
leukopenia (23%, 32%), anemia (21%, 9%), upper respiratory tract
infection (27%, 11%), bronchitis (5%, 47%), nasopharyngitis (2%,
35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (55%,
39%), rash (32%, 8%), fatigue (23%, 11%), asthenia (0%, 30%),
muscle spasm (0%, 33%), and pyrexia (8%, 21%)
- After at least one prior therapy: The most common
adverse reactions reported in ≥20% (REVLIMID/dex vs dex/placebo):
fatigue (44% vs 42%), neutropenia (42% vs 6%), constipation (41% vs
21%), diarrhea (39% vs 27%), muscle cramp (33% vs 21%), anemia (31%
vs 24%), pyrexia (28% vs 23%), peripheral edema (26% vs 21%),
nausea (26% vs 21%), back pain (26% vs 19%), upper respiratory
tract infection (25% vs 16%), dyspnea (24% vs 17%), dizziness (23%
vs 17%), thrombocytopenia (22% vs 11%), rash (21% vs 9%), tremor
(21% vs 7%), and weight decreased (20% vs 15%)
Myelodysplastic
Syndromes
- Grade 3 and 4 adverse events reported in ≥ 5% of patients with
del 5q MDS were neutropenia (53%), thrombocytopenia (50%),
pneumonia (7%), rash (7%), anemia (6%), leukopenia (5%), fatigue
(5%), dyspnea (5%), and back pain (5%)
- Adverse events reported in ≥15% of del 5q MDS patients
(REVLIMID): thrombocytopenia (61.5%), neutropenia (58.8%), diarrhea
(49%), pruritus (42%), rash (36%), fatigue (31%), constipation
(24%), nausea (24%), nasopharyngitis (23%), arthralgia (22%),
pyrexia (21%), back pain (21%), peripheral edema (20%), cough
(20%), dizziness (20%), headache (20%), muscle cramp (18%), dyspnea
(17%), pharyngitis (16%), epistaxis (15%), asthenia (15%), upper
respiratory tract infection (15%)
Mantle Cell Lymphoma
- Grade 3 and 4 adverse events reported in ≥5% of patients
treated with REVLIMID in the MCL trial (N=134) included neutropenia
(43%), thrombocytopenia (28%), anemia (11%), pneumonia (9%),
leukopenia (7%), fatigue (7%), diarrhea (6%), dyspnea (6%), and
febrile neutropenia (6%)
- Adverse events reported in ≥15% of patients treated with
REVLIMID in the MCL trial included neutropenia (49%),
thrombocytopenia (36%), fatigue (34%), anemia (31%), diarrhea
(31%), nausea (30%), cough (28%), pyrexia (23%), rash (22%),
dyspnea (18%), pruritus (17%), peripheral edema (16%), constipation
(16%), and leukopenia (15%)
Follicular Lymphoma/Marginal Zone
Lymphoma
- Fatal adverse reactions occurred in 6 patients (1.5%) receiving
REVLIMID + rituximab across both trials. Fatal adverse reactions (1
each) included: cardio-respiratory arrest, arrhythmia,
cardiopulmonary failure, multiple organ dysfunction syndrome,
sepsis, and acute kidney injury. The most frequent serious adverse
reaction that occurred in the REVLIMID/rituximab arm was febrile
neutropenia (3.0%).
- Grade 3 and 4 adverse reactions reported in ≥5% of patients
treated in the FL/MZL trial with REVLIMID + rituximab were:
neutropenia (50%) and leukopenia (7%)
- Adverse reactions reported in ≥15% of patients with FL/MZL
treated with REVLIMID + rituximab were: neutropenia (58%), diarrhea
(31%), constipation (26%), cough (24%), fatigue (22%), rash (22%),
pyrexia (21%), leukopenia (20%), pruritis (20%), upper respiratory
tract infections (18%), abdominal pain (18%), anemia (16%),
headache (15%), thrombocytopenia (15%)
DRUG INTERACTIONS
Periodically monitor digoxin plasma levels due to increased Cmax
and AUC with concomitant REVLIMID therapy. Patients taking
concomitant therapies such as erythropoietin-stimulating agents or
estrogen-containing therapies may have an increased risk of
thrombosis. It is not known whether there is an interaction between
dexamethasone and warfarin. Close monitoring of PT and INR is
recommended in patients with MM taking concomitant warfarin
USE IN SPECIFIC POPULATIONS
- Pregnancy: See Boxed WARNINGS: If pregnancy does occur
during treatment, immediately discontinue the drug and refer
patient to an obstetrician/gynecologist experienced in reproductive
toxicity for further evaluation and counseling. There is a REVLIMID
pregnancy exposure registry that monitors pregnancy outcomes in
females exposed to REVLIMID during pregnancy as well as female
partners of male patients who are exposed to REVLIMID. This
registry is also used to understand the root cause for the
pregnancy. Report any suspected fetal exposure to REVLIMID to the
FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene
Corporation at 1-888-423-5436
- Lactation: There is no information regarding the
presence of lenalidomide in human milk, the effects of REVLIMID on
the breastfed infant, or the effects of REVLIMID on milk
production. Because many drugs are excreted in human milk and
because of the potential for adverse reactions in breastfed infants
from REVLIMID, advise female patients not to breastfeed during
treatment with REVLIMID
- Renal Impairment: Adjust the starting dose of REVLIMID
based on the creatinine clearance value and in patients on
dialysis
Please see full Prescribing Information, including Boxed
WARNINGS, for REVLIMID.
About INREBIC®
INREBIC® (fedratinib) is indicated for the treatment of adult
patients with intermediate-2 or high-risk primary or secondary
(post-polycythemia vera or post-essential thrombocythemia)
myelofibrosis (MF).
IMPORTANT SAFETY
INFORMATION
WARNING: ENCEPHALOPATHY INCLUDING WERNICKE’S
Serious and fatal encephalopathy, including Wernicke’s, has
occurred in patients treated with INREBIC. Wernicke’s
encephalopathy is a neurologic emergency. Assess thiamine levels in
all patients prior to starting INREBIC, periodically during
treatment, and as clinically indicated. Do not start INREBIC in
patients with thiamine deficiency; replete thiamine prior to
treatment initiation. If encephalopathy is suspected, immediately
discontinue INREBIC and initiate parenteral thiamine. Monitor until
symptoms resolve or improve and thiamine levels normalize.
WARNINGS AND PRECAUTIONS
Encephalopathy, including Wernicke’s: Serious and fatal
encephalopathy, including Wernicke’s encephalopathy, has occurred
in INREBIC-treated patients. Serious cases were reported in 1.3%
(8/608) of patients treated with INREBIC in clinical trials and
0.16% (1/608) of cases were fatal.
Wernicke’s encephalopathy is a neurologic emergency resulting
from thiamine (Vitamin B1) deficiency. Signs and symptoms of
Wernicke’s encephalopathy may include ataxia, mental status
changes, and ophthalmoplegia (e.g., nystagmus, diplopia). Any
change in mental status, confusion, or memory impairment should
raise concern for potential encephalopathy, including Wernicke’s,
and prompt a full evaluation including a neurologic examination,
assessment of thiamine levels, and imaging. Assess thiamine levels
in all patients prior to starting INREBIC, periodically during
treatment, and as clinically indicated. Do not start INREBIC in
patients with thiamine deficiency; replete thiamine prior to
treatment initiation. If encephalopathy is suspected, immediately
discontinue INREBIC and initiate parenteral thiamine. Monitor until
symptoms resolve or improve and thiamine levels normalize.
Anemia: New or worsening Grade 3 anemia occurred in 34%
of INREBIC-treated patients. The median time to onset of the first
Grade 3 anemia was approximately 2 months, with 75% of cases
occurring within 3 months. Mean hemoglobin levels reached nadir
after 12 to 16 weeks with partial recovery and stabilization after
16 weeks. Red blood cell transfusions were received by 51% of
INREBIC-treated patients and permanent discontinuation of INREBIC
occurred due to anemia in 1% of patients. Consider dose reduction
for patients who become red blood cell transfusion dependent
Thrombocytopenia: New or worsening Grade ≥3
thrombocytopenia during the randomized treatment period occurred in
12% of INREBIC-treated patients. The median time to onset of the
first Grade 3 thrombocytopenia was approximately 1 month; with 75%
of cases occurring within 4 months. Platelet transfusions were
received by 3.1% INREBIC-treated patients. Permanent
discontinuation of treatment due to thrombocytopenia and bleeding
that required clinical intervention both occurred in 2.1% of
INREBIC-treated patients. Obtain a complete blood count (CBC) at
baseline, periodically during treatment, and as clinically
indicated. For Grade 3 thrombocytopenia with active bleeding or
Grade 4 thrombocytopenia, interrupt INREBIC until resolved to less
than or equal to Grade 2 or baseline. Restart dose at 100 mg daily
below the last given dose and monitor platelets as clinically
indicated.
Gastrointestinal Toxicity: Gastrointestinal toxicities
are the most frequent adverse reactions in INREBIC-treated
patients. During the randomized treatment period, diarrhea occurred
in 66% of patients, nausea in 62% of patient and vomiting in 39% of
patients. Grade 3 diarrhea 5% and vomiting 3.1% occurred. The
median time to onset of any grade nausea, vomiting, and diarrhea
was 1 day, with 75% of cases occurring within 2 weeks of treatment.
Consider providing appropriate prophylactic anti-emetic therapy
(e.g., 5-HT3 receptor antagonists) during INREBIC treatment. Treat
diarrhea with anti-diarrheal medications promptly at the first
onset of symptoms. Grade 3 or higher nausea, vomiting, or diarrhea
not responsive to supportive measures within 48 hours, interrupt
INREBIC until resolved to Grade 1 or less or baseline. Restart dose
at 100 mg daily below the last given dose. Monitor thiamine levels
and replete as needed.
Hepatic Toxicity: Elevations of ALT and AST (all grades)
during the randomized treatment period occurred in 43% and 40%,
respectively, with Grade 3 or 4 in 1% and 0%, respectively, of
INREBIC-treated patients. The median time to onset of any grade
transaminase elevation was approximately 1 month, with 75% of cases
occurring within 3 months. Monitor hepatic function at baseline,
periodically during treatment, and as clinically indicated. For
Grade 3 or higher ALT and/or AST elevations (greater than 5 × ULN),
interrupt INREBIC dose until resolved to Grade 1 or less or to
baseline. Restart dose at 100 mg daily below the last given dose.
If re-occurrence of a Grade 3 or higher elevation of ALT/AST,
discontinue treatment with INREBIC.
Amylase and Lipase Elevation: Grade 3 or higher amylase
2% and/or lipase 10% elevations developed in INREBIC-treated
patients. The median time to onset of any grade amylase or lipase
elevation was 15 days, with 75% of cases occurring within 1 month
of starting treatment. One patient developed pancreatitis in the
fedratinib clinical development program (n=608) and pancreatitis
resolved with treatment discontinuation. Monitor amylase and lipase
at baseline, periodically during treatment, and as clinically
indicated. For Grade 3 or higher amylase and/or lipase elevations,
interrupt INREBIC until resolved to Grade 1 or less or to baseline.
Restart dose at 100 mg daily below the last given dose.
ADVERSE REACTIONS: The most common adverse reactions for
INREBIC treated vs. placebo were diarrhea (66% vs. 16%), nausea
(62% vs. 15%), anemia (40% vs. 14%), and vomiting (39% vs. 5%).
Dosage interruptions due to an adverse reaction during the
randomized treatment period occurred in 21% of patients who
received INREBIC. Adverse reactions requiring dosage interruption
in >3% of patients who received INREBIC included diarrhea and
nausea. Dosage reductions due to an adverse reaction during the
randomized treatment period occurred in 19% of patients who
received INREBIC. Adverse reactions requiring dosage reduction in
>2% of patients who received INREBIC included anemia (6%),
diarrhea (3%), vomiting (3%), and thrombocytopenia (2%).
DRUG INTERACTIONS: Coadministration of INREBIC with a
strong CYP3A4 inhibitor increases fedratinib exposure. Increased
exposure may increase the risk of adverse reactions. Consider
alternative therapies that do not strongly inhibit CYP3A4 activity.
Alternatively, reduce the dose of INREBIC when administering with a
strong CYP3A4 inhibitor. Avoid INREBIC with strong and moderate
CYP3A4 inducers. Avoid INREBIC with dual CYP3A4 and CYP2C19
inhibitor. Coadministration of INREBIC with drugs that are CYP3A4
substrates, CYP2C19 substrates, or CYP2D6 substrates increases the
concentrations of these drugs, which may increase the risk of
adverse reactions of these drugs. Monitor for adverse reactions and
adjust the dose of drugs that are CYP3A4, CYP2C19, or CYP2D6
substrates as necessary when coadministered with INREBIC.
PREGNANCY/LACTATION: Consider the benefits and risks of
INREBIC for the mother and possible risks to the fetus when
prescribing INREBIC to a pregnant woman. Due to the potential for
serious adverse reactions in a breastfed child, advise patients not
to breastfeed during treatment with INREBIC, and for at least 1
month after the last dose.
RENAL IMPAIRMENT: Reduce INREBIC dose when administered
to patients with severe renal impairment. No modification of the
starting dose is recommended for patients with mild to moderate
renal impairment. Due to potential increase of exposure, patients
with preexisting moderate renal impairment require more intensive
safety monitoring, and if necessary, dose modifications based on
adverse reactions.
HEPATIC IMPAIRMENT: Avoid use of INREBIC in patients with
severe hepatic impairment.
Please see full Prescribing Information, including Boxed
WARNING.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global biopharmaceutical company engaged primarily in
the discovery, development and commercialization of innovative
therapies for the treatment of cancer and inflammatory diseases
through next-generation solutions in protein homeostasis,
immuno-oncology, epigenetics, immunology and neuro-inflammation.
For more information, please visit www.celgene.com. Follow Celgene
on Social Media: Twitter, Pinterest, LinkedIn, Facebook and
YouTube.
FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements, which
are generally statements that are not historical facts.
Forward-looking statements can be identified by the words
"expects," "anticipates," "believes," "intends," "estimates,"
"plans," "will," "outlook" and similar expressions. Forward-looking
statements are based on management's current plans, estimates,
assumptions and projections, and speak only as of the date they are
made. We undertake no obligation to update any forward-looking
statement in light of new information or future events, except as
otherwise required by law. Forward-looking statements involve
inherent risks and uncertainties, most of which are difficult to
predict and are generally beyond our control. Actual results or
outcomes may differ materially from those implied by the
forward-looking statements as a result of the impact of a number of
factors, many of which are discussed in more detail in our Annual
Report on Form 10-K and our other reports filed with the U.S.
Securities and Exchange Commission, including factors related to
the proposed transaction between Bristol-Myers Squibb and Celgene,
such as, but not limited to, the risks that: management's time and
attention is diverted on transaction related issues, including the
planned divestiture of OTEZLA®; disruption from the proposed
transaction makes it more difficult to maintain business,
contractual and operational relationships; legal proceedings are
instituted against Bristol-Myers Squibb, Celgene or the combined
company; and Bristol-Myers Squibb, Celgene or the combined company
is unable to retain key personnel.
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version on businesswire.com: https://www.businesswire.com/news/home/20191106005580/en/
Celgene Corporation Investors: Nina Goworek +1-908-673-9711
ngoworek@celgene.com or
Media: +1-908-673-2275 media@celgene.com
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