THOUSAND OAKS, Calif.,
Dec. 7, 2017 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced that new clinical data
and analyses from 33 abstracts, including six oral presentations,
evaluating approved medicines and investigational immuno-oncology
agents from the Company's robust hematology portfolio and pipeline
will be presented at the 59th American Society of
Hematology (ASH) Annual Meeting & Exposition in Atlanta, Dec. 9-12,
2017.
The breadth and depth of data to be presented at ASH highlight
Amgen's commitment to advancing treatment options for patients with
some of the most difficult-to-treat blood cancers and disorders.
Notably at ASH, positive overall survival (OS) results from the
Phase 3 ASPIRE trial will be detailed for the first time in an oral
presentation, which showed the addition of KYPROLIS®
(carfilzomib) to lenalidomide and dexamethasone (KRd) significantly
extended OS versus lenalidomide and dexamethasone (Rd) alone in
patients with relapsed or refractory multiple myeloma. The safety
data from ASPIRE was consistent with the known safety profile of
KYPROLIS.
"At Amgen, we take great pride in our heritage and commitment to
developing innovative, life-changing treatments for some of the
toughest cancers," said David Reese,
M.D., senior vice president of Translational Sciences and Oncology
at Amgen. "The range of data from our broad portfolio of treatments
and innovative pipeline assets together demonstrate the
considerable potential of Amgen's investment in oncology and blood
cancers. Results being presented at ASH also highlight the
potential of BiTEs, our bispecific T cell engager molecules, to
activate a patient's immune system to fight cancer, and demonstrate
the benefit our approved medicines can provide for patients with
blood cancers across the disease continuum."
Translating Research into Improved Survival for
Patients
New results to be presented at ASH demonstrate how
two Amgen medicines – KYPROLIS and BLINCYTO®
(blinatumomab) – improved OS in adult patients with relapsed
multiple myeloma and Philadelphia
chromosome-negative (Ph-) relapsed or refractory B-cell precursor
acute lymphoblastic leukemia (ALL), respectively.
KYPROLIS-based regimens (KRd) and KYPROLIS® and
dexamethasone (Kd) are the first and only to demonstrate improved
OS over two standards of care (Rd) and Velcade®
(bortezomib) and dexamethasone (Vd) in two Phase 3 trials in
relapsed or refractory patients with multiple myeloma. In addition
to ASPIRE, OS data from the Phase 3 ENDEAVOR trial will be detailed
in presentations, which showed how Kd were superior in improving OS
versus Vd across subgroups of relapsed or refractory patients
with multiple myeloma.
BLINCYTO is the first-and-only approved CD19-directed CD3
BiTE® immunotherapy and the only treatment to
demonstrate a statistically significant improvement inOS in
patients with relapsed or refractory ALL. Results from an
exploratory analysis evaluating the OS benefit of BLINCYTO
maintenance therapy in patients with Ph- relapsed or refractory
B-cell precursor ALL will be highlighted during a poster session.
BLINCYTO maintenance therapy reduced the risk of death by 41
percent versus no maintenance therapy. Adverse events were
consistent with the established safety profile in adult patients
with Ph- relapsed or refractory B-cell precursor ALL. Overall
safety event rates were lower in maintenance vs. induction or
consolidation cycles.
The U.S. Food and Drug Administration (FDA) has accepted for
priority review the supplemental Biologics License Application
(sBLA) for BLINCYTO for the treatment of patients with frontline or
relapsed B-cell precursor ALL with minimal residual disease (MRD),
the first application to be submitted for this indication. The
Prescription Drug User Fee Act (PDUFA) target action date is
March 29, 2018. Results from the
Phase 2 BLAST study upon which the sBLA is based were presented at
the 57th Annual ASH Meeting and Exposition in
2015.
Advancing Outcomes Across the Disease Continuum
New
real-world data in patients with multiple myeloma bone disease will
also be presented. Of note, a study evaluating patterns and
predictors of initiation of intravenous bisphosphonates among
multiple myeloma patients will be highlighted in an oral session.
In the study, less than half of patients initiated bisphosphonate
treatment in the two years after diagnosis to prevent fractures and
other skeletal-related events, underscoring the need to manage the
bone health of patients with myeloma more proactively.
Spotlighting Robust Amgen Immuno-Oncology Pipeline
An
array of data from the Amgen oncology pipeline will be presented at
ASH, spanning a variety of modalities across immuno-oncology.
Notably, four presentations will focus on the potential of Amgen's
BiTE® platform as a novel immuno-oncology approach to
treating a variety of hematologic cancers. Amgen is the only
company with an approved BiTE® (BLINCYTO) and
believes that this technology platform holds significant
potential in other hematologic cancers and in solid
tumors.
Amgen Investor Webcast
Amgen will host a webcast
investor meeting at ASH on Saturday, Dec. 9, 2017,
at 11:30 a.m. ET. David M. Reese, M.D., senior vice
president of Translational Sciences and Oncology at Amgen, together
with other members of Amgen's management team and a clinical
investigator, will participate to discuss the Company's oncology
program, including Amgen's BiTE® immunotherapy
platform.
Live audio of the investor meeting will be broadcast over the
internet simultaneously and will be available to members of the
news media, investors and the general public.
The webcast, as with other selected presentations regarding
developments in Amgen's business given at certain
investor and medical conferences, can be accessed on Amgen's
website, www.amgen.com, under Investors. Information regarding
presentation times, webcast availability and webcast links are
noted on Amgen's Investor Relations Events Calendar. The
webcast will be archived and available for replay for at least 90
days after the event.
Key Amgen presentation information for ASH 2017 is featured
here. A complete listing of abstracts can be found on the ASH
website.
Translating Research into Improved Survival for
Patients
- Overall Survival (OS) of Patients With Relapsed/Refractory
Multiple Myeloma (RRMM) Treated With Carfilzomib, Lenalidomide, and
Dexamethasone (KRd) Versus Lenalidomide and Dexamethasone (Rd):
Final Analysis From the Randomized Phase 3 ASPIRE
Trial
Abstract #743, Oral Presentation, Monday, Dec. 11 at 2:45
p.m. ET in Georgia World
Congress Center, Building C, Level 1, Hall C1
- Overall Survival of Relapsed/Refractory Multiple Myeloma
Patients Treated With Carfilzomib and Dexamethasone vs Bortezomib
and Dexamethasone: Results From the Phase 3 ENDEAVOR Study
According to Age Subgroup
Abstract #1885, Poster
Presentation, Saturday, Dec. 9 at
5:30 p.m. ET in Georgia World Congress Center, Building A,
Level 1, Hall A2
- Overall Survival of Patients With Relapsed Multiple Myeloma
Treated With Carfilzomib and Dexamethasone Versus Bortezomib and
Dexamethasone According to Prior Line of Therapy and Previous
Exposure to Bortezomib: Secondary Analysis of the Phase 3 ENDEAVOR
Study
Abstract #1850, Poster Presentation, Saturday, Dec. 9 at 5:30
p.m. ET in Georgia World
Congress Center, Building A, Level 1, Hall A2
- Maintenance Therapy With Blinatumomab in Adults With
Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL):
Overall Survival in Adults Enrolled In a Phase 3 Open-Label
Trial
Abstract #2552, Poster Presentation, Sunday, Dec. 10 at 6 p.m.
ET in Georgia World
Congress Center, Building A, Level 1, Hall A2
Advancing Outcomes Across the Disease Continuum
- Patterns and Predictors of Initiation of Intravenous
Bisphosphonates Among Patients With Multiple Myeloma in
the United States
Abstract
#534, Oral Presentation, Sunday, Dec.
10 at 4:30 p.m. ET in
Georgia World Congress Center,
Building B, Level 2, B206
- Multiple Myeloma Patients and Risk of SRE – Real-World
Evidence in US Oncology Clinics
Abstract #2171, Poster
Presentation, Saturday, Dec. 9 at
5:30 p.m. ET in Georgia World Congress Center, Building A,
Level 1, Hall A2
Spotlighting Robust Amgen Immuno-Oncology Pipeline
- Preclinical Characterization of AMG 424, a Novel Humanized T
Cell–Recruiting Bispecific Anti-CD3/CD38 Antibody
Abstract
#500, Oral Presentation, Sunday, Dec.
10 at 4:30 p.m. ET in
Georgia World Congress Center,
Building B, Level 3, B308-B309
- CD33/CD3-Bispecific T-Cell Engaging (BiTE®)
Antibody Constructs Efficiently Target Monocytic CD14+HLA-DRlow
IDO+AML-MDSCs
Abstract #1363, Poster Presentation,
Saturday, Dec. 9 at 5:30 p.m. ET in Georgia World Congress Center, Building A,
Level 1, Hall A2
- Evaluation of a FLT3 BiTE® for Acute Myeloid
Leukemia
Abstract #1354, Poster Presentation, Saturday, Dec. 9 at 5:30
p.m. ET in Georgia World
Congress Center, Building A, Level 1, Hall A2
- Generation of a Half-life Extended Anti-CD19
BiTE® Antibody Construct Compatible With Once-weekly
Dosing for Treatment of CD19-positive Malignancies
Abstract
#2815, Poster Presentation, Sunday, Dec.
10 at 6 p.m. ET in
Georgia World Congress Center,
Building A, Level 1, Hall A2
- AMG 592 is an Investigational IL-2 Mutein That Induces
Highly Selective Expansion of Regulatory T cells
Abstract
#696, Oral Presentation, Monday, Dec.
11 at 2:45 p.m. ET in
Georgia World Congress Center,
Building C, Level 1, C108-C109
About
KYPROLIS® (carfilzomib)
Proteasomes
play an important role in cell function and growth by breaking down
proteins that are damaged or no longer
needed.1 KYPROLIS has been shown to block
proteasomes, leading to an excessive build-up of proteins within
cells.1 In some cells, KYPROLIS can cause cell
death, especially in myeloma cells because they are more likely to
contain a higher amount of abnormal proteins.1,2
KYPROLIS is approved in the U.S. for the following:
- In combination with dexamethasone or with lenalidomide plus
dexamethasone for the treatment of patients with relapsed or
refractory multiple myeloma who have received one to three lines of
therapy.
- As a single agent for the treatment of patients with relapsed
or refractory multiple myeloma who have received one or more lines
of therapy.
KYPROLIS is also approved in Argentina, Australia, Bahrain, Canada, Hong
Kong, Israel, Japan, Kuwait, Lebanon, Macao, Mexico, Thailand, Colombia, S. Korea, Qatar, Switzerland, United
Arab Emirates, Turkey,
Russia, Brazil, India, Oman
and the European Union. Additional regulatory applications for
KYPROLIS are underway and have been submitted to health authorities
worldwide.
IMPORTANT SAFETY INFORMATION
Cardiac Toxicities
- New onset or worsening of pre-existing cardiac failure (e.g.,
congestive heart failure, pulmonary edema, decreased ejection
fraction), restrictive cardiomyopathy, myocardial ischemia, and
myocardial infarction including fatalities have occurred following
administration of KYPROLIS. Some events occurred in patients with
normal baseline ventricular function. Death due to cardiac arrest
has occurred within one day of KYPROLIS administration.
- Monitor patients for clinical signs or symptoms of cardiac
failure or cardiac ischemia. Evaluate promptly if cardiac toxicity
is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse
events until recovery, and consider whether to restart KYPROLIS at
1 dose level reduction based on a benefit/risk assessment.
- While adequate hydration is required prior to each dose in
Cycle 1, monitor all patients for evidence of volume overload,
especially patients at risk for cardiac failure. Adjust total fluid
intake as clinically appropriate in patients with baseline cardiac
failure or who are at risk for cardiac failure.
- Patients ≥ 75 years, the risk of cardiac failure is increased.
Patients with New York Heart Association Class III and IV heart
failure, recent myocardial infarction, conduction abnormalities,
angina, or arrhythmias may be at greater risk for cardiac
complications and should have a comprehensive medical assessment
(including blood pressure and fluid management) prior to starting
treatment with KYPROLIS and remain under close follow-up.
Acute Renal Failure
- Cases of acute renal failure and renal insufficiency adverse
events (including renal failure) have occurred in patients
receiving KYPROLIS. Acute renal failure was reported more
frequently in patients with advanced relapsed and refractory
multiple myeloma who received KYPROLIS monotherapy. Monitor renal
function with regular measurement of the serum creatinine and/or
estimated creatinine clearance. Reduce or withhold dose as
appropriate.
Tumor Lysis Syndrome
- Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes,
have occurred in patients receiving KYPROLIS. Patients with
multiple myeloma and a high tumor burden should be considered at
greater risk for TLS. Adequate hydration is required prior to each
dose in Cycle 1, and in subsequent cycles as needed. Consider uric
acid lowering drugs in patients at risk for TLS. Monitor for
evidence of TLS during treatment and manage promptly. Withhold
KYPROLIS until TLS is resolved.
Pulmonary Toxicity
- Acute Respiratory Distress Syndrome (ARDS), acute respiratory
failure, and acute diffuse infiltrative pulmonary disease such as
pneumonitis and interstitial lung disease have occurred in patients
receiving KYPROLIS. Some events have been fatal. In the event of
drug-induced pulmonary toxicity, discontinue KYPROLIS.
Pulmonary Hypertension
- Pulmonary arterial hypertension (PAH) was reported in patients
treated with KYPROLIS. Evaluate with cardiac imaging and/or other
tests as indicated. Withhold KYPROLIS for PAH until resolved or
returned to baseline and consider whether to restart KYPROLIS based
on a benefit/risk assessment.
Dyspnea
- Dyspnea was reported in patients treated with KYPROLIS.
Evaluate dyspnea to exclude cardiopulmonary conditions including
cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3
or 4 dyspnea until resolved or returned to baseline. Consider
whether to restart KYPROLIS based on a benefit/risk
assessment.
Hypertension
- Hypertension, including hypertensive crisis and hypertensive
emergency, has been observed with KYPROLIS. Some of these events
have been fatal. Monitor blood pressure regularly in all patients.
If hypertension cannot be adequately controlled, withhold KYPROLIS
and evaluate. Consider whether to restart KYPROLIS based on a
benefit/risk assessment.
Venous Thrombosis
- Venous thromboembolic events (including deep venous thrombosis
and pulmonary embolism) have been observed with KYPROLIS.
Thromboprophylaxis is recommended for patients being treated with
the combination of KYPROLIS with dexamethasone or with lenalidomide
plus dexamethasone. The thromboprophylaxis regimen should be based
on an assessment of the patient's underlying risks.
- Patients using oral contraceptives or a hormonal method of
contraception associated with a risk of thrombosis should consider
an alternative method of effective contraception during treatment
with KYPROLIS in combination with dexamethasone or lenalidomide
plus dexamethasone.
Infusion Reactions
- Infusion reactions, including life-threatening reactions, have
occurred in patients receiving KYPROLIS.
- Symptoms include fever, chills, arthralgia, myalgia, facial
flushing, facial edema, vomiting, weakness, shortness of breath,
hypotension, syncope, chest tightness, or angina. These reactions
can occur immediately following or up to 24 hours after
administration of KYPROLIS. Premedicate with dexamethasone to
reduce the incidence and severity of infusion reactions. Inform
patients of the risk and of symptoms of an infusion reaction and to
contact a physician immediately if they occur.
Hemorrhage
- Fatal or serious cases of hemorrhage have been reported in
patients receiving KYPROLIS. Hemorrhagic events have included
gastrointestinal, pulmonary, and intracranial hemorrhage and
epistaxis. Promptly evaluate signs and symptoms of blood loss.
Reduce or withhold dose as appropriate.
Thrombocytopenia
- KYPROLIS causes thrombocytopenia with recovery to baseline
platelet count usually by the start of the next cycle.
Thrombocytopenia was reported in patients receiving KYPROLIS.
Monitor platelet counts frequently during treatment with KYPROLIS.
Reduce or withhold dose as appropriate.
Hepatic Toxicity and Hepatic Failure
- Cases of hepatic failure, including fatal cases, have been
reported during treatment with KYPROLIS. KYPROLIS can cause
increased serum transaminases. Monitor liver enzymes regularly
regardless of baseline values. Reduce or withhold dose as
appropriate.
Thrombotic Microangiopathy
- Cases of thrombotic microangiopathy, including thrombotic
thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS),
including fatal outcome have occurred in patients receiving
KYPROLIS. Monitor for signs and symptoms of TTP/HUS. Discontinue
KYPROLIS if diagnosis is suspected. If the diagnosis of TTP/HUS is
excluded, KYPROLIS may be restarted. The safety of reinitiating
KYPROLIS therapy in patients previously experiencing TTP/HUS is not
known.
Posterior Reversible Encephalopathy Syndrome (PRES)
- Cases of PRES have occurred in patients receiving KYPROLIS.
PRES was formerly known as Reversible Posterior Leukoencephalopathy
Syndrome. Consider a neuro-radiological imaging (MRI) for onset of
visual or neurological symptoms. Discontinue KYPROLIS if PRES is
suspected and evaluate. The safety of reinitiating KYPROLIS therapy
in patients previously experiencing PRES is not known.
Increased Fatal and Serious Toxicities in Combination with
Melphalan and Prednisone in Newly Diagnosed
Transplant‐ineligible Patients
- In a clinical trial of transplant‐ineligible patients with
newly diagnosed multiple myeloma comparing KYPROLIS, melphalan, and
prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a
higher incidence of serious and fatal adverse events was observed
in patients in the KMP arm. KYPROLIS in combination with
melphalan and prednisone is not indicated for transplant‐ineligible
patients with newly diagnosed multiple myeloma.
Embryo-fetal Toxicity
- KYPROLIS can cause fetal harm when administered to a pregnant
woman based on its mechanism of action and findings in
animals.
- Females of reproductive potential should be advised to avoid
becoming pregnant while being treated with KYPROLIS. Males of
reproductive potential should be advised to avoid fathering a child
while being treated with KYPROLIS. If this drug is used during
pregnancy, or if pregnancy occurs while taking this drug, the
patient should be apprised of the potential hazard to the
fetus.
ADVERSE REACTIONS
- The most common adverse reactions occurring in at least 20% of
patients treated with KYPROLIS in the combination therapy trials:
anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia,
pyrexia, insomnia, muscle spasm, cough, upper respiratory tract
infection, hypokalemia.
- The most common adverse reactions occurring in at least 20% of
patients treated with KYPROLIS in monotherapy trials: anemia,
fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea,
headache, cough, edema peripheral.
Please see full prescribing information
at www.kyprolis.com.
About
BLINCYTO® (blinatumomab)
BLINCYTO is a
bispecific CD19-directed CD3 T cell engager (BiTE®)
antibody construct that binds specifically to CD19 expressed on the
surface of cells of B-lineage origin and CD3 expressed on the
surface of T cells.
BLINCYTO was granted breakthrough therapy and priority review
designations by the FDA, and is now approved in the U.S. for
the treatment of relapsed or refractory B-cell precursor ALL
in adults and children.
In November 2015, BLINCYTO was granted conditional
marketing authorization in the EU for the treatment of adults with
Ph- relapsed or refractory B-cell precursor ALL. Additional
regulatory applications for BLINCYTO are underway and have been
submitted to health authorities worldwide.
About BiTE® Technology
Bispecific T
cell engager (BiTE®) antibody constructs are a type of
immunotherapy being investigated for fighting cancer by helping the
body's immune system to detect and target malignant cells. The
modified antibodies are designed to bridge T cells to tumor cells,
using the patient's own immune system to eradicate their cancer.
BiTE® antibody constructs help place the T cells
within reach of the targeted cell, with the intent of allowing T
cells to inject toxins and trigger the cancer cell to die
(apoptosis). BiTE® antibody constructs are currently
being investigated for their potential to treat a wide variety of
cancers. For more information,
visit www.biteantibodies.com.
BLINCYTO® U.S. Product Safety
Information
Indication and Important Safety Information, including Boxed
WARNINGS, for BLINCYTO® (blinatumomab) for
injection, for intravenous use
INDICATION
BLINCYTO® is indicated for the treatment of
relapsed or refractory B-cell precursor acute lymphoblastic
leukemia (ALL) in adults and children.
IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL
TOXICITIES
- Cytokine Release Syndrome (CRS), which may be
life-threatening or fatal, occurred in patients receiving
BLINCYTO®. Interrupt or discontinue BLINCYTO® as
recommended.
- Neurological toxicities, which may be severe,
life-threatening or fatal, occurred in patients receiving
BLINCYTO®. Interrupt or discontinue BLINCYTO® as
recommended.
Contraindications
BLINCYTO® is
contraindicated in patients with a known hypersensitivity to
blinatumomab or to any component of the product formulation.
Warnings and Precautions
- Cytokine Release Syndrome (CRS): CRS, which may be
life-threatening or fatal, occurred in patients receiving
BLINCYTO®. Infusion reactions have occurred and may be
clinically indistinguishable from manifestations of CRS. Closely
monitor patients for signs and symptoms of serious events such as
pyrexia, headache, nausea, asthenia, hypotension, increased alanine
aminotransferase (ALT), increased aspartate aminotransferase (AST),
increased total bilirubin (TBILI), disseminated intravascular
coagulation (DIC), capillary leak syndrome (CLS), and
hemophagocytic lymphohistiocytosis/macrophage activation syndrome
(HLH/MAS). Interrupt or discontinue BLINCYTO® as outlined in the
Prescribing Information (PI).
- Neurological Toxicities: Approximately 65% of patients
receiving BLINCYTO® in clinical trials experienced
neurological toxicities. The median time to the first event was
within the first 2 weeks of BLINCYTO® treatment and the
majority of events resolved. The most common (≥ 10%) manifestations
of neurological toxicity were headache and tremor. Severe,
life-threatening, or fatal neurological toxicities occurred in
approximately 13% of patients, including encephalopathy,
convulsions, speech disorders, disturbances in consciousness,
confusion and disorientation, and coordination and balance
disorders. Monitor patients for signs or symptoms and interrupt or
discontinue BLINCYTO® as outlined in the PI.
- Infections: Approximately 25% of patients receiving
BLINCYTO® experienced serious infections, some of which
were life-threatening or fatal. Administer prophylactic antibiotics
and employ surveillance testing as appropriate during treatment.
Monitor patients for signs or symptoms of infection and treat
appropriately, including interruption or discontinuation of
BLINCYTO® as needed.
- Tumor Lysis Syndrome (TLS): TLS, which may be life-threatening
or fatal, has been observed. Preventive measures, including
pretreatment nontoxic cytoreduction and on-treatment hydration,
should be used during BLINCYTO® treatment. Monitor
patients for signs and symptoms of TLS and interrupt or discontinue
BLINCYTO® as needed to manage these events.
- Neutropenia and Febrile Neutropenia, including life-threatening
cases, have been observed. Monitor appropriate laboratory
parameters during BLINCYTO® infusion and interrupt
BLINCYTO® if prolonged neutropenia occurs.
- Effects on Ability to Drive and Use Machines: Due to the
possibility of neurological events, including seizures, patients
receiving BLINCYTO® are at risk for loss of
consciousness, and should be advised against driving and engaging
in hazardous occupations or activities such as operating heavy or
potentially dangerous machinery while BLINCYTO® is being
administered.
- Elevated Liver Enzymes: Transient elevations in liver enzymes
have been associated with BLINCYTO® treatment with a median time to
onset of 3 days. In patients receiving BLINCYTO®, although
the majority of these events were observed in the setting of CRS,
some cases of elevated liver enzymes were observed outside the
setting of CRS, with a median time to onset of 19 days. Grade 3 or
greater elevations in liver enzymes occurred in 7% of patients
outside the setting of CRS and resulted in treatment
discontinuation in less than 1% of patients. Monitor ALT,
AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start
of and during BLINCYTO® treatment. BLINCYTO®
treatment should be interrupted if transaminases rise to > 5
times the upper limit of normal (ULN) or if TBILI rises to > 3
times ULN.
- Pancreatitis: Fatal pancreatitis has been reported in patients
receiving BLINCYTO® in combination with dexamethasone in
clinical trials and the post-marketing setting. Evaluate patients
who develop signs and symptoms of pancreatitis and interrupt or
discontinue BLINCYTO® and dexamethasone as needed.
- Leukoencephalopathy: Although the clinical significance is
unknown, cranial magnetic resonance imaging (MRI) changes showing
leukoencephalopathy have been observed in patients receiving
BLINCYTO®, especially in patients previously treated
with cranial irradiation and antileukemic chemotherapy.
- Preparation and administration errors have occurred with
BLINCYTO® treatment. Follow instructions for preparation
(including admixing) and administration in the PI strictly to
minimize medication errors (including underdose and overdose).
- Immunization: Vaccination with live virus vaccines is not
recommended for at least 2 weeks prior to the start of
BLINCYTO® treatment, during treatment, and until immune
recovery following last cycle of BLINCYTO®.
- Risk of Serious Adverse Reactions in Pediatric Patients due to
Benzyl Alcohol Preservative: Serious and fatal adverse reactions
including "gasping syndrome," which is characterized by central
nervous system depression, metabolic acidosis, and gasping
respirations, can occur in neonates and infants treated with benzyl
alcohol-preserved drugs including BLINCYTO® (with
preservative). When prescribing BLINCYTO® (with
preservative) for pediatric patients, consider combined daily
metabolic load of benzyl alcohol from all sources including
BLINCYTO® (with preservative) and other drugs containing
benzyl alcohol. The minimum amount of benzyl alcohol at which
serious adverse reactions may occur is not known. Due to the
addition of bacteriostatic saline, 7-day bags of
BLINCYTO® solution for infusion with preservative
contain benzyl alcohol and are not recommended for use in any
patients weighing < 22 kg.
Adverse Reactions
- The most common adverse reactions
in Philadelphia chromosome-negative relapsed or
refractory B-cell precursor ALL (TOWER Study) (≥ 20%) in the
BLINCYTO® arm were infections (bacterial and pathogen
unspecified), pyrexia, headache, infusion-related reactions,
anemia, febrile neutropenia, thrombocytopenia, and neutropenia.
Serious adverse reactions were reported in 62% of patients. The
most common serious adverse reactions (≥ 2%) included febrile
neutropenia, pyrexia, sepsis, pneumonia, overdose, septic shock,
CRS, bacterial sepsis, device related infection, and
bacteremia.
- Adverse reactions that were observed more frequently (≥ 10%) in
the pediatric population compared to the adult population were
pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs.
24%), infusion-related reaction (49% vs. 34%), thrombocytopenia
(34% vs. 21%), leukopenia (24% vs. 11%), and weight increased (17%
vs. 6%).
- In pediatric patients less than 2 years old (infants), the
incidence of neurologic toxicities was not significantly different
than for the other age groups, but its manifestations were
different; the only event terms reported were agitation, headache,
insomnia, somnolence, and irritability. Infants also had an
increased incidence of hypokalemia (50%) compared to other
pediatric age cohorts (15-20%) or adults (17%).
Dosage and Administration Guidelines
- BLINCYTO® is administered as a continuous
intravenous infusion at a constant flow rate using an infusion pump
which should be programmable, lockable, non-elastomeric, and have
an alarm.
- It is very important that the instructions for preparation
(including admixing) and administration provided in the full
Prescribing Information are strictly followed to minimize
medication errors (including underdose and overdose).
Please see full Prescribing Information, including Boxed
WARNINGS and Medication Guide, for BLINCYTO®.
About XGEVA® (denosumab)
XGEVA
targets the RANKL pathway to prevent the formation, function and
survival of osteoclasts, which break down bone. As a monoclonal
antibody, XGEVA is not cleared by the kidneys. XGEVA is indicated
for the prevention of skeletal-related events in patients with bone
metastases from solid tumors. In the U.S., XGEVA currently has
a limitation of use noting that it is not indicated for the
prevention of skeletal-related events in patients with multiple
myeloma. XGEVA is also indicated for the treatment of adults and
skeletally mature adolescents with giant cell tumor of bone that is
unresectable or where surgical resection is likely to result in
severe morbidity. XGEVA is also indicated in the U.S. for the
treatment of hypercalcemia of malignancy refractory to
bisphosphonate therapy.
U.S. Important Safety Information
Hypocalcemia
Pre-existing hypocalcemia must be
corrected prior to initiating therapy with XGEVA®.
XGEVA® can cause severe symptomatic hypocalcemia,
and fatal cases have been reported. Monitor calcium levels,
especially in the first weeks of initiating therapy, and administer
calcium, magnesium, and vitamin D as necessary. Monitor levels more
frequently when XGEVA® is administered with other
drugs that can also lower calcium levels. Advise patients to
contact a healthcare professional for symptoms of hypocalcemia.
An increased risk of hypocalcemia has been observed in clinical
trials of patients with increasing renal dysfunction, most commonly
with severe dysfunction (creatinine clearance less than 30
mL/minute and/or on dialysis), and with inadequate/no calcium
supplementation. Monitor calcium levels and calcium and vitamin D
intake.
Hypersensitivity
XGEVA® is
contraindicated in patients with known clinically significant
hypersensitivity to XGEVA®, including anaphylaxis that
has been reported with use of XGEVA®. Reactions may
include hypotension, dyspnea, upper airway edema, lip swelling,
rash, pruritus, and urticaria. If an anaphylactic or other
clinically significant allergic reaction occurs, initiate
appropriate therapy and discontinue XGEVA® therapy
permanently.
Drug Products with Same Active Ingredient
Patients
receiving XGEVA® should not take
Prolia® (denosumab).
Osteonecrosis of the Jaw
Osteonecrosis of the
jaw (ONJ) has been reported in patients receiving
XGEVA®, manifesting as jaw pain, osteomyelitis,
osteitis, bone erosion, tooth or periodontal infection, toothache,
gingival ulceration, or gingival erosion. Persistent pain or slow
healing of the mouth or jaw after dental surgery may also be
manifestations of ONJ. In clinical trials in patients with osseous
metastasis, the incidence of ONJ was higher with longer
duration of exposure.
Patients with a history of tooth extraction, poor oral hygiene,
or use of a dental appliance are at a greater risk to develop ONJ.
Other risk factors for the development of ONJ include
immunosuppressive therapy, treatment with angiogenesis inhibitors,
systemic corticosteroids, diabetes, and gingival infections.
Perform an oral examination and appropriate preventive dentistry
prior to the initiation of XGEVA® and periodically
during XGEVA® therapy. Advise patients regarding
oral hygiene practices. Avoid invasive dental procedures during
treatment with XGEVA®. Consider temporarily interrupting
XGEVA® therapy if an invasive dental procedure must
be performed.
Patients who are suspected of having or who develop ONJ while on
XGEVA® should receive care by a dentist or an oral
surgeon. In these patients, extensive dental surgery to treat ONJ
may exacerbate the condition.
Atypical Subtrochanteric and Diaphyseal Femoral
Fracture
Atypical femoral fracture has been reported
with XGEVA®. These fractures can occur anywhere in the
femoral shaft from just below the lesser trochanter to above the
supracondylar flare and are transverse or short oblique in
orientation without evidence of comminution.
Atypical femoral fractures most commonly occur with minimal or
no trauma to the affected area. They may be bilateral and many
patients report prodromal pain in the affected area, usually
presenting as dull, aching thigh pain, weeks to months before a
complete fracture occurs. A number of reports note that patients
were also receiving treatment with glucocorticoids (e.g.
prednisone) at the time of fracture. During
XGEVA® treatment, patients should be advised to
report new or unusual thigh, hip, or groin pain. Any patient who
presents with thigh or groin pain should be suspected of having an
atypical fracture and should be evaluated to rule out an incomplete
femur fracture. Patients presenting with an atypical femur fracture
should also be assessed for symptoms and signs of fracture in the
contralateral limb. Interruption of XGEVA® therapy
should be considered, pending a risk/benefit assessment, on an
individual basis.
Hypercalcemia Following Treatment Discontinuation in Patients
with Growing Skeletons
Clinically significant hypercalcemia has been reported in
XGEVA® treated patients with growing skeletons,
weeks to months following treatment discontinuation. Monitor
patients for signs and symptoms of hypercalcemia and treat
appropriately.
Embryo-Fetal Toxicity
XGEVA® can cause
fetal harm when administered to a pregnant woman. Based on findings
in animals, XGEVA® is expected to result in adverse
reproductive effects.
Advise females of reproductive potential to use highly effective
contraception during therapy, and for at least 5 months after the
last dose of XGEVA®. Apprise the patient of the
potential hazard to a fetus if XGEVA® is used
during pregnancy or if the patient becomes pregnant while patients
are exposed to XGEVA®.
Adverse Reactions
The most common adverse
reactions in patients receiving XGEVA® with bone
metastasis from solid tumors were fatigue/asthenia,
hypophosphatemia, and nausea. The most common serious adverse
reaction was dyspnea. The most common adverse reactions resulting
in discontinuation were osteonecrosis and hypocalcemia.
The most common adverse reactions in patients receiving
XGEVA® for giant cell tumor of bone were
arthralgia, headache, nausea, back pain, fatigue, and pain in
extremity. The most common serious adverse reactions were
osteonecrosis of the jaw and osteomyelitis. The most common adverse
reactions resulting in discontinuation of XGEVA® were
osteonecrosis of the jaw and tooth abscess or tooth
infection.
The most common adverse reactions in patients receiving
XGEVA® for hypercalcemia of malignancy were nausea,
dyspnea, decreased appetite, headache, peripheral edema, vomiting,
anemia, constipation, and diarrhea.
Denosumab is also marketed as Prolia® in other
indications.
Please
visit www.amgen.com or www.xgeva.com for Full
U.S. Prescribing Information.
About Amgen's Commitment to Oncology
Amgen Oncology is
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such as those that have been resistant to drugs, those that
progress rapidly through the body and those where limited treatment
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With decades of experience providing therapies for cancer patients,
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About Amgen
Amgen is committed to unlocking
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Amgen focuses on areas of high unmet medical need and
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CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(Media)
Kristen Neese, 805-313-8267
(Media)
Arvind Sood, 805-447-1060
(Investors)
References
- Moreau P, Richardson PG, Cavo M, et al. Proteasome Inhibitors
in Multiple Myeloma: 10 Years Later. Blood. 2012;
120(5):947-959.
- Kortuem KM and Stewart AK. Carfilzomib. Blood. 2012;
121(6):893-897.
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