THOUSAND OAKS, Calif.,
Dec. 2, 2019 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced new clinical data from
its oncology in-line products and pipeline that will be presented
at the 61st American Society of Hematology (ASH) Annual
Meeting & Exposition in Orlando, Dec. 7-10,
2019.
The Phase 3 CANDOR study, which was accepted as a late-breaking
abstract, evaluated KYPROLIS® (carfilzomib) in
combination with dexamethasone and DARZALEX®
(daratumumab) (KdD) compared to KYPROLIS and dexamethasone alone
(Kd) in patients with relapsed or refractory multiple myeloma.
Additional data from Amgen's hematology franchise will include new
results from the bispecific T cell engager (BiTE®)
platform across multiple blood cancers, including multiple myeloma,
acute myeloid leukemia, acute lymphoblastic leukemia (ALL), diffuse
large B-cell lymphoma and non-Hodgkin's lymphoma.
"The late-breaking abstract from the CANDOR study evaluating
KYPROLIS with an anti-CD38 monoclonal antibody demonstrates that by
combining these two powerful agents, this regimen has the potential
to be practice-changing for the treatment of patients with relapsed
or refractory multiple myeloma," said David
M. Reese, M.D., executive vice president of Research and
Development at Amgen.
Additionally, data from study AALL1331 conducted by
the Children's Oncology Group (COG) evaluating
BLINCYTO® (blinatumomab) versus chemotherapy in
first relapse of childhood B-lymphoblastic leukemia (B-ALL) were
accepted as a late-breaking abstract. AALL1331 is sponsored by the
Cancer Therapy Evaluation Program of the National Cancer
Institute (NCI), part of the National Institutes of
Health, and is conducted by the NCI-funded
COG. Amgen provided BLINCYTO for the study under
a Collaborative Research and Development Agreement
between the NCI and Amgen. BLINCYTO, which was approved in
2014, is the first and only approved BiTE molecule.
"The data being presented at ASH demonstrate our commitment to
furthering the science of our in-line products, including KYPROLIS
and BLINCYTO, while also advancing our pipeline of innovative BiTE
molecules which could potentially provide new treatment approaches
for patients across blood cancers for which there remains high
unmet need," continued Reese.
A complete listing of Amgen's abstracts is available on the ASH
website. Notable abstracts include:
KYPROLIS Amgen Sponsored Abstracts
- Carfilzomib, Dexamethasone, and Daratumumab Versus
Carfilzomib and Dexamethasone for the Treatment of Patients with
Relapsed or Refractory Multiple Myeloma (RRMM): Primary
Analysis Results from the Randomized, Open-Label, Phase 3 Study
CANDOR (NCT03158688)
LBA-6, Tuesday, Dec. 10 from 7:30 –
9 a.m. ET in Hall D, Level 2
- Efficacy And Safety Of
Carfilzomib-Lenalidomide-Dexamethasone (KRd) In NDMM: Pooled
Analysis Of 4 Single-Arm Studies
Abstract #1891, Poster
Presentation, Poster I, Saturday, Dec.
7 from 5:30 – 7:30 p.m. ET in
Hall B, Level 2
- Phase 1b Study Of Carfilzomib
In Combination With Induction Chemotherapy In Children With
Relapsed Or Refractory Acute Lymphoblastic Leukemia
(ALL)
Abstract #3873, Poster Presentation, Poster III, Monday, Dec. 9 from 6 – 8
p.m. ET in Hall B, Level 2
KYPROLIS Investigator Led
Abstracts
- Daratumumab, Carfilzomib, Lenalidomide and Dexamethasone
(Dara-KRd) Induction, Autologous Transplantation and
Post-Transplant, Response-Adapted, Measurable Residual Disease
(MRD)-Based Dara-KRd Consolidation in Patients with Newly Diagnosed
Multiple Myeloma (NDMM)
Abstract #860, Oral Presentation,
Monday, Dec. 9 at 4:45 p.m. in Hall E2
- Weekly Carfilzomib, Lenalidomide, Dexamethasone And
Daratumumab (wKRd-D) Combination Therapy Provides Unprecedented MRD
Negativity Rates In Newly Diagnosed Multiple Myeloma: A Clinical
And Correlative Phase 2 Study
Abstract #862, Oral
Presentation, Monday, Dec. 9 at
5:15 p.m. in Hall E2, Level 2
BLINCYTO Amgen Sponsored Abstracts
- Blinatumomab in Pediatric Patients With R/R B-Cell Precursor
And Molecularly Resistant ALL: Updated Analysis of 110 Patients
Treated in an Expanded Access Study (RIALTO)
Abstract #1294,
Poster Presentation, Poster I, Saturday,
Dec. 7 from 5:30 – 7:30 p.m.
ET in Hall B, Level 2
- Open-Label, Phase 2 Study of Blinatumomab After First-Line
Rituximab-Chemotherapy in Adults with Newly Diagnosed, High-Risk
Diffuse Large B-Cell Lymphoma
Abstract #4077, Poster
Presentation, Poster III, Monday, Dec.
9 from 6 – 8 p.m. ET in Hall
B, Level 2
- Treatment of Adults with Relapsed/Refractory Philadelphia
Chromosome Negative Acute Lymphoblastic Leukemia with Blinatumomab
in a Real-World Setting: Results from the Neuf
Study
Abstract #2627, Poster Presentation, Poster II,
Sunday, Dec. 8 from 6 – 8 p.m. ET in Hall B, Level 2
- Treatment of Adults with Minimal Residual Disease (MRD)
Positive Acute Lymphoblastic Leukemia with Blinatumomab in a
Real-World Setting: Results from the Neuf Study
Abstract
#2624, Poster Presentation, Poster II, Sunday, Dec. 8 from 6 – 8
p.m. ET in Hall B, Level 2
BLINCYTO Investigator Led Abstracts
- A Randomized Phase 3 Trial of Blinatumomab vs Chemotherapy
as Post-Reinduction Therapy in High & Intermediate Risk First
Relapse of B-ALL in Children & AYAs Demonstrates Superior
Survival and Tolerability of Blin: A Report from Children's
Oncology Group Study AALL1331
LBA-1, Late-Breaking Oral Presentation, Tuesday, Dec. 10 from 7:30 – 9 a.m. ET in Hall D, Level 2
- A Phase IB Study of Blinatumomab (blina) in Patients with B
Cell Acute Lymphoblastic Leukemia (ALL) and B-Cell Non-Hodgkin
Lymphoma (NHL) As Post-Allogeneic Blood or Marrow Transplant
(allo-BMT) Remission Maintenance
Abstract #778, Oral
Presentation, Monday, Dec. 9 at
3:30 p.m. in Chapin Theater (W320),
Level 3
- Blinatumomab/Lenalidomide in Relapsed/Refractory
Non-Hodgkin's Lymphoma: A Phase I California Cancer Consortium
Study of Safety, Efficacy and Immune Correlative
Analysis
Abstract #760, Oral Presentation, Monday, Dec. 9 at 3:30
p.m. in W304ABCD, Level 3
- Updated Results of A Phase II Study of Reduced-Intensity
Chemotherapy With Mini-Hyper-CVD In Combination With Inotuzumab
Ozogamicin, With or Without Blinatumomab, in Older Adults with
Newly Diagnosed Philadelphia Chromosome-Negative Acute
Lymphoblastic Leukemia
Abstract #823, Oral Presentation,
Monday, Dec. 9 at 4:30 p.m. in Tangerine 1 (WF1), Level 2
XGEVA® (denosumab)
- Progression Free Survival Analysis Of Denosumab Vs
Zoledronic Acid In Intent To Transplant Multiple Myeloma Patients
Based On Treatment Regimen And Baseline
Characteristics
Abstract #606, Oral Presentation,
Monday, Dec. 9 at 8:15 a.m. in Sunburst Room (W340)
Oncology Pipeline
- AMG 701 Potently Induces Anti-Multiple Myeloma (MM)
Functions Of T Cells And IMiDs Further Enhance Its Efficacy To
Prevent MM Relapse In Vivo
Abstract #135, Oral Presentation,
Saturday, Dec. 7 at 10 a.m. ET in Valencia A (W415A), Level 4
- Preliminary Results From A Phase 1 First-in-Human Study Of
AMG 673, A Novel Half-life Extended (HLE) Anti-CD33/CD3
BiTE® (Bispecific T-cell Engager) Molecule In Patients
With Relapsed/Refractory (R/R) Acute Myeloid Leukemia
(AML)
Abstract #833, Oral Presentation, Monday, Dec. 9 at 5:30
p.m. ET in Chapin Theater (W320), Level 3
About CANDOR
CANDOR, a randomized, open-label Phase 3
study of KYPROLIS, dexamethasone and DARZALEX (KdD) compared to
KYPROLIS and dexamethasone (Kd), has evaluated 466 relapsed or
refractory multiple myeloma patients who have received one to three
prior therapies. Patients were treated until disease progression.
The primary endpoint was PFS, and the key secondary endpoints were
overall response rate, minimal residual disease and overall
survival. PFS was defined as time from randomization until disease
progression or death from any cause.
In the first arm, patients received KYPROLIS twice weekly at 56
mg/m2 and dexamethasone in combination with DARZALEX. In
the second arm (control), patients received KYPROLIS twice weekly
at 56 mg/m2 and dexamethasone.
CANDOR was initiated as part of a collaboration with Janssen,
and under the terms of the agreement, Janssen co-funded the study.
For more information about this trial, please
visit www.clinicaltrials.gov under trial identification number
NCT03158688.
About the COG AALL1331 Study
The COG AALL1331 study is
a risk-stratified, randomized, Phase 3 trial of blinatumomab in
first relapse of pediatric B-ALL to evaluate disease-free survival
(DFS) of high-risk (HR) and intermediate-risk (IR) relapsed B-ALL
patients who are randomized following induction block 1
chemotherapy to receive either two intensive chemotherapy blocks or
two 5-week blocks of blinatumomab. It also compares the DFS of low
risk (LR) relapse B-ALL patients who are randomized following block
1 chemotherapy to receive either chemotherapy alone or chemotherapy
plus blinatumomab. Key secondary endpoints include overall survival
of HR, IR, and LR relapsed B-ALL patients. This is a global study
that is being conducted in Australia, Canada, New
Zealand and United States. Click here to read
about the trial on ClinicalTrials.gov.
About Multiple Myeloma
Multiple myeloma is an
incurable blood cancer, characterized by a recurring pattern of
remission and relapse.1 It is a rare and
life-threatening disease that accounts for approximately one
percent of all cancers.2,3 Worldwide, approximately
160,000 people are diagnosed with multiple myeloma each year, and
106,000 patient deaths are reported on an annual
basis.2
About KYPROLIS® (carfilzomib)
Proteasomes
play an important role in cell function and growth by breaking down
proteins that are damaged or no longer needed.4 KYPROLIS
has been shown to block proteasomes, leading to an excessive
build-up of proteins within cells.5 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.4,5
Since its first approval in 2012, more than 125,000 patients
worldwide have received KYPROLIS. 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 Algeria, Argentina, Australia, Bahrain, Belarus, Brazil, Canada, Chile, Colombia, Ecuador, Egypt, European Union, Hong Kong, India, Israel, Japan, Jordan, Kuwait, Lebanon, Macao, Malaysia, Mexico, Morocco, New
Zealand, Oman, Philippines, Qatar, Russia, Saudi
Arabia, Singapore, S.
Korea, Switzerland, Taiwan, Thailand, Turkey and United
Arab Emirates.
Important U.S. KYPROLIS® (carfilzomib) 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 administration.
- Monitor patients for signs or symptoms of cardiac failure or
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 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.
- For 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 prior to starting treatment with KYPROLIS and remain
under close follow-up with fluid management.
Acute Renal Failure
- Cases of acute renal failure, including some fatal renal
failure events, and renal insufficiency adverse events (including
renal failure) have occurred. 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. Patients with 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,
and withhold until 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. Some
events have been fatal. In the event of drug‐induced pulmonary
toxicity, discontinue KYPROLIS.
Pulmonary Hypertension
- Pulmonary arterial hypertension (PAH) was reported. 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 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 based on a benefit/risk assessment.
Hypertension
- Hypertension, including hypertensive crisis and hypertensive
emergency, has been observed, some fatal. Control hypertension
prior to starting KYPROLIS. Monitor blood pressure regularly in all
patients. If hypertension cannot be adequately controlled, withhold
KYPROLIS and evaluate. Consider whether to restart based on a
benefit/risk assessment.
Venous Thrombosis
- Venous thromboembolic events (including deep venous thrombosis
and pulmonary embolism) have been observed. 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 hormonal contraception associated with a risk of
thrombosis should consider an alternative method of effective
contraception during treatment.
Infusion Reactions
- Infusion reactions, including life‐threatening reactions, have
occurred. 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. Premedicate with dexamethasone to reduce the
incidence and severity of infusion reactions. Inform patients of
the risk and of symptoms and seek immediate medical attention if
they occur.
Hemorrhage
- Fatal or serious cases of hemorrhage have been reported.
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. Monitor
platelet counts frequently during treatment. Reduce or withhold
dose as appropriate.
Hepatic Toxicity and Hepatic Failure
- Cases of hepatic failure, including fatal cases, have occurred.
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. Monitor for signs and
symptoms of TTP/HUS. Discontinue if diagnosis is suspected. If the
diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The
safety of reinitiating KYPROLIS is not known.
Posterior Reversible Encephalopathy Syndrome (PRES)
- Cases of PRES have occurred in patients receiving KYPROLIS. If
PRES is suspected, discontinue and evaluate with appropriate
imaging. The safety of reinitiating KYPROLIS 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. KMP 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.
- Females of reproductive potential should be advised to avoid
becoming pregnant while being treated with KYPROLIS and for 6
months following the final dose. Males of reproductive potential
should be advised to avoid fathering a child while being treated
with KYPROLIS and for 3 months following the final dose. 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 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 in monotherapy trials:
anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea,
diarrhea, headache, cough, edema peripheral
Please see full Prescribing Information at
www.kyprolis.com.
About ALL and MRD
ALL is a rapidly progressing cancer
of the blood and bone marrow that occurs in both adults and
children.6,7 Poor outcomes have been observed in
patients who achieve first or second complete hematologic remission
but are persistently MRD-positive, which currently remains
detectable at the molecular level after treatment.8,9
For more information about MRD, please visit AmgenOncology.com.
About BiTE® Technology
Bispecific T cell
engager (BiTE®) technology is a targeted immuno-oncology
platform that is designed to engage patients' own T cells to any
tumor-specific antigen, activating the cytotoxic potential of T
cells to eliminate detectable cancer. The BiTE immuno-oncology
platform has the potential to treat different tumor types through
tumor-specific antigens. The BiTE platform leads to off-the-shelf
solutions, which have the potential to make innovative T cell
treatment available to all providers when their patients need it.
Amgen is advancing more than a dozen BiTE molecules across a broad
range of hematologic malignancies and solid tumors, further
investigating BiTE technology with the goal of enhancing patient
experience and therapeutic potential.
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.
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 engage two different targets
simultaneously, thereby juxtaposing T cells (a type of white blood
cell capable of killing other cells perceived as threats) to cancer
cells. 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.
BLINCYTO was granted breakthrough therapy and priority review
designations by the U.S. Food and Drug Administration and is
approved in the U.S. for the treatment of:
- relapsed or refractory B-cell precursor ALL in adults and
children.
- B-cell precursor ALL in first or second complete remission with
minimal residual disease (MRD) greater than or equal to 0.1% in
adults and children.
This indication is approved under accelerated approval based on MRD
response rate and hematological relapse-free survival. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in the confirmatory
trials.
In the European Union (EU), BLINCYTO is indicated as monotherapy
for the treatment of:
- adults with Philadelphia
chromosome negative CD19 positive relapsed or refractory
B-precursor acute lymphoblastic leukaemia (ALL).
- adults with Philadelphia
chromosome negative CD19 positive B-precursor ALL in first or
second complete remission with minimal residual disease (MRD)
greater than or equal to 0.1%.
- paediatric patients aged 1 year or older with Philadelphia chromosome negative CD19 positive
B-precursor ALL which is refractory or in relapse after receiving
at least two prior therapies or in relapse after receiving prior
allogeneic hematopoietic stem cell transplantation
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®
and treat with corticosteroids 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 15% of patients with R/R ALL
and in 7% of patients with MRD-positive ALL. The median time to
onset of CRS is 2 days after the start of infusion and the median
time to resolution of CRS was 5 days among cases that resolved.
Closely monitor and advise patients to contact their healthcare
professional for signs and symptoms of serious adverse events such
as fever, headache, nausea, asthenia, hypotension, increased
alanine aminotransferase (ALT), increased aspartate
aminotransferase (AST), increased total bilirubin (TBILI), and
disseminated intravascular coagulation (DIC). The manifestations of
CRS after treatment with BLINCYTO® overlap with
those of infusion reactions, capillary leak syndrome, and
hemophagocytic histiocytosis/macrophage activation syndrome. If
severe CRS occurs, interrupt BLINCYTO® until CRS
resolves. Discontinue BLINCYTO® permanently if
life-threatening CRS occurs. Administer corticosteroids for severe
or life-threatening CRS.
- 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. Manifestations of neurological toxicity included cranial
nerve disorders. Monitor patients for signs or symptoms and
interrupt or discontinue BLINCYTO® as outlined in the
PI.
- Infections: Approximately 25% of patients receiving
BLINCYTO® in clinical trials experienced serious
infections such as sepsis, pneumonia, bacteremia, opportunistic
infections, and catheter-site 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), 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 (including, but not limited to, white blood cell count
and absolute neutrophil count) 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 approximately 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,
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 the 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 (≥ 20%) in clinical trial
experience of patients with MRD-positive B-cell precursor ALL
(BLAST Study) treated with BLINCYTO® were pyrexia (91%),
infusion-related reactions (77%), headache (39%), infections
(pathogen unspecified 39%), tremor (31%), and chills (28%). Serious
adverse reactions were reported in 61% of patients. The most common
serious adverse reactions (≥ 2%) included pyrexia, tremor,
encephalopathy, aphasia, lymphopenia, neutropenia, overdose, device
related infection, seizure, and staphylococcal infection.
- The most common adverse reactions (≥ 20%) in clinical trial
experience of patients with Philadelphia chromosome-negative relapsed or
refractory B-cell precursor ALL (TOWER Study) treated with
BLINCYTO® 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 adults with relapsed or
refractory B-cell precursor ALL 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 and medication guide for
BLINCYTO at www.BLINCYTO.com.
About Multiple Myeloma and Bone Complications
Multiple
myeloma is the second most common hematologic cancer, and it
develops in plasma cells located in the bone marrow
microenvironment.2,10 It is typically characterized by
osteolytic bone lesions as well as renal failure, which are both
part of diagnosis (CRAB criteria).11 Each year an
estimated 160,000 new cases of multiple myeloma are diagnosed
worldwide, resulting in more than 106,000 deaths per
year.2
More than 90 percent of patients develop osteolytic lesions
during the course of the disease.12 Preventing bone
complications is a critical aspect of caring for patients with
multiple myeloma, because these events can result in significant
morbidity.13 Current treatment options to prevent bone
complications are limited to bisphosphonates, including zoledronic
acid, which are cleared through the kidneys.14
Approximately 60 percent of all multiple myeloma patients have or
will develop renal impairment over the course of the
disease.15
About XGEVA® (denosumab)
XGEVA targets the
RANKL pathway to prevent the formation, function and survival of
osteoclasts, which break down bone. XGEVA is indicated for the
prevention of skeletal-related events in patients with multiple
myeloma and in patients with bone metastases from solid tumors.
XGEVA is also indicated for 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 and for the treatment of hypercalcemia of
malignancy refractory to bisphosphonate therapy.
INDICATIONS
XGEVA® is indicated for the
prevention of skeletal-related events in patients with multiple
myeloma and in patients with bone metastases from solid tumors.
XGEVA® is indicated for 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 indicated for the treatment
of hypercalcemia of malignancy refractory to bisphosphonate
therapy.
IMPORTANT SAFETY INFORMATION
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 cancer, 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 Giant Cell Tumor of Bone (GCTB) and in Patients with Growing
Skeletons
Clinically significant hypercalcemia requiring
hospitalization and complicated by acute renal injury has been
reported in XGEVA®-treated patients with GCTB and in
patients with growing skeletons within one year of treatment
discontinuation. Monitor patients for signs and symptoms of
hypercalcemia after treatment discontinuation and treat
appropriately.
Multiple Vertebral Fractures (MVF) Following Treatment
Discontinuation
Multiple vertebral fractures (MVF) have been
reported following discontinuation of treatment with denosumab.
Patients at higher risk for MVF include those with risk factors for
or a history of osteoporosis or prior fractures. When
XGEVA® treatment is discontinued, evaluate the
individual patient's risk for vertebral fractures.
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 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.
For multiple myeloma patients receiving XGEVA®, the
most common adverse reactions were diarrhea, nausea, anemia, back
pain, thrombocytopenia, peripheral edema, hypocalcemia, upper
respiratory tract infection, rash, and headache. The most common
serious adverse reaction was pneumonia. The most common adverse
reaction resulting in discontinuation of XGEVA® was
osteonecrosis of the jaw.
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.
Please visit www.xgeva.com for Full U.S. Prescribing
Information.
About Amgen Oncology
Amgen Oncology is searching for
and finding answers to incredibly complex questions that will
advance care and improve lives for cancer patients and their
families. Our research drives us to understand the disease in the
context of the patient's life – not just their cancer journey – so
they can take control of their lives.
For the last four decades, we have been dedicated to discovering
the firsts that matter in oncology and to finding ways to reduce
the burden of cancer. Building on our heritage, Amgen continues to
advance the largest pipeline in the Company's history, moving with
great speed to advance those innovations for the patients who need
them.
At Amgen, we are driven by our commitment to transform the lives
of cancer patients and keep them at the center of everything we
do.
For more information, follow us on
www.twitter.com/amgenoncology.
About Amgen
Amgen is committed to unlocking the
potential of biology for patients suffering from serious illnesses
by discovering, developing, manufacturing and delivering innovative
human therapeutics. This approach begins by using tools like
advanced human genetics to unravel the complexities of disease and
understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages
its expertise to strive for solutions that improve health outcomes
and dramatically improve people's lives. A biotechnology pioneer
since 1980, Amgen has grown to be one of the world's leading
independent biotechnology companies, has reached millions of
patients around the world and is developing a pipeline of medicines
with breakaway potential.
For more information, visit www.amgen.com and follow us on
www.twitter.com/amgen.
Forward-Looking Statements
This news release contains
forward-looking statements that are based on the current
expectations and beliefs of Amgen. All statements, other than
statements of historical fact, are statements that could be deemed
forward-looking statements, including any statements on the
outcome, benefits and synergies of collaboration with any other
company, including BeiGene, Ltd., or the acquisition of
Otezla® (apremilast), including anticipated Otezla sales
growth and the timing of non-GAAP EPS accretion, as well as
estimates of revenues, operating margins, capital expenditures,
cash, other financial metrics, expected legal, arbitration,
political, regulatory or clinical results or practices, customer
and prescriber patterns or practices, reimbursement activities and
outcomes and other such estimates and results. Forward-looking
statements involve significant risks and uncertainties, including
those discussed below and more fully described in the Securities
and Exchange Commission reports filed by Amgen, including our most
recent annual report on Form 10-K and any subsequent periodic
reports on Form 10-Q and current reports on Form 8-K. Unless
otherwise noted, Amgen is providing this information as of the date
of this news release and does not undertake any obligation to
update any forward-looking statements contained in this document as
a result of new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual
results may differ materially from those we project. Discovery or
identification of new product candidates or development of new
indications for existing products cannot be guaranteed and movement
from concept to product is uncertain; consequently, there can be no
guarantee that any particular product candidate or development of a
new indication for an existing product will be successful and
become a commercial product. Further, preclinical results do not
guarantee safe and effective performance of product candidates in
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sometimes, even adequately modeled by computer or cell culture
systems or animal models. The length of time that it takes for us
to complete clinical trials and obtain regulatory approval for
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we or others could identify safety, side effects or manufacturing
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Our results may be affected by our ability to successfully
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CONTACT: Amgen, Thousand
Oaks
Jessica Akopyan, 805-447-0974
Trish Hawkins, 805-447-5631
(Media)
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(Investors)
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