BLINCYTO® Added to
Multiphase Consolidation Chemotherapy Reduced Risk of Death by
58% Showing Superior Overall Survival Versus Chemotherapy
Alone
First and Only Bispecific T-cell
Engager (BiTE®) Therapy for
Consolidation Treatment Regardless of Measurable Residual Disease
(MRD) Status
THOUSAND
OAKS, Calif., June 14,
2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today
announced the U.S. Food and Drug Administration (FDA) has approved
BLINCYTO® (blinatumomab) for the treatment of adult and
pediatric patients one month or older with CD19-positive
Philadelphia chromosome-negative
B-cell precursor acute lymphoblastic leukemia (B-ALL) in the
consolidation phase, regardless of measurable residual disease
(MRD) status.
"B-ALL is an aggressive blood cancer with enduring high unmet
need. BLINCYTO has helped thousands of patients with B-ALL over the
last 10 years. Today's approval in the frontline consolidation
phase, regardless of MRD status, allows us to reach more patients
than ever with this transformative, first-in-class Bispecific
T-cell Engager (BiTE®) therapy," said Jay Bradner, M.D., executive vice president,
Research and Development, and chief scientific officer at
Amgen.
The approval marks the third indication for BLINCYTO and is
based primarily on the Phase 3 E1910 clinical trial led by
ECOG-ACRIN Cancer Research Group that studied patients with newly
diagnosed Philadelphia
chromosome-negative B-ALL receiving postinduction consolidation
treatment, which aims to deepen remission to achieve durable
responses. Study results demonstrated that BLINCYTO added to
multiphase consolidation chemotherapy showed superior overall
survival (OS) versus chemotherapy alone. The 3-year OS was 84.8% in
the BLINCYTO plus chemotherapy arm (n=112) and 69% in the
chemotherapy arm (n=112), with the hazard ratio for OS of 0.42.
With a median follow-up of 4.5 years, the 5-year OS was 82.4% in
the BLINCYTO plus chemotherapy arm and 62.5% in the chemotherapy
arm.
"In the E1910 study, blinatumomab reduced risk of death and
showed a remarkable improvement in overall survival," said
Selina M. Luger, M.D., professor of
hematology-oncology at the University of
Pennsylvania's Perelman School of Medicine and Abramson
Cancer Center, chair of the ECOG-ACRIN Leukemia Committee and an
investigator on the study. "This approval redefines the standard of
care for patients with B-ALL and provides them with a more
effective treatment option than standard chemotherapy alone."
"The risk of B-ALL recurrence after the initial phase of
treatment is relatively high, making this approval for patients
noteworthy," said E. Anders Kolb,
M.D., president and chief executive officer of The Leukemia &
Lymphoma Society. "B-ALL is the most common type of ALL and having
another effective option available earlier in a patient's treatment
journey is critical for clinicians who are working to give these
patients more time with their loved ones."
The E1910 study was designed and conducted independently from
industry. ECOG-ACRIN sponsored the trial with public funding from
the National Cancer Institute (NCI), part of the National
Institutes of Health (NIH). Other NCI-funded network groups took
part in the study. In addition, Amgen provided BLINCYTO and support
through an NCI Cooperative Research and Development Agreement.
About Acute Lymphoblastic Leukemia (ALL)
ALL, also
known as acute lymphoblastic leukemia, is a fast-growing type
of blood cancer that develops in the bone marrow and can sometimes
spread to other parts of the body, including the lymph nodes,
liver, spleen, and central nervous system. ALL is a rare disease,
with 6,540 new cases diagnosed in the U.S. in 2023 affecting both
children and adults.1 B-ALL begins in immature cells
that would normally develop into B-cell lymphocytes, which are
white blood cells that grow in bone marrow.2,3 B-ALL is
the most common type of ALL, constituting approximately 75% of
cases in adults.4
About
BLINCYTO® (blinatumomab)
BLINCYTO is the
first globally approved BiTE® immuno-oncology therapy
that targets CD19 surface antigens on B
cells. BiTE® molecules fight cancer by helping the
body's immune system detect and target malignant cells by engaging
T cells (a type of white blood cell capable of killing other cells
perceived as threats) to cancer cells. By bringing T cells near
cancer cells, the T cells can inject toxins and trigger cancer cell
death (apoptosis). BiTE® immuno-oncology therapies 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. FDA and is approved in
the U.S. for the treatment of:
- Adult and pediatric patients one month or older with
CD19-positive Philadelphia
chromosome-negative B-ALL during the consolidation phase of
multiphase therapy.
- CD19-positive B-ALL in first or second complete remission with
MRD greater than or equal to 0.1% in adults and pediatric patients
one month or older.
- Relapsed or refractory CD19-positive B-ALL in adults and
pediatric patients one month or older.
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-ALL.
Patients with Philadelphia
chromosome-positive B-ALL should have failed treatment with at
least two tyrosine kinase inhibitors (TKIs) and have no alternative
treatment options.
- Adults with Philadelphia
chromosome-negative CD19-positive B-ALL in first or second complete
remission with MRD greater than or equal to 0.1%.
- Pediatric patients aged 1 year or older with Philadelphia chromosome-negative CD19-positive
B-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.
- Pediatric patients aged 1 year or older with high-risk first
relapsed Philadelphia
chromosome-negative CD19-positive B-ALL as part of the
consolidation therapy.
INDICATIONS
BLINCYTO® (blinatumomab) is indicated for the
treatment of CD19-positive B-cell precursor acute lymphoblastic
leukemia (ALL) in adult and pediatric patients one month and older
with:
- Philadelphia
chromosome-negative disease in the consolidation phase of
multiphase chemotherapy.
- Minimal residual disease (MRD) greater than or equal to 0.1% in
first or second complete remission.
- Relapsed or refractory disease.
BLINCYTO® IMPORTANT SAFETY
INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL
TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY
SYNDROME
- 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, including immune effector
cell-associated neurotoxicity syndrome (ICANS) 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®. 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 (CLS), and hemophagocytic
histiocytosis/macrophage activation syndrome (MAS). Using all of
these terms to define CRS in clinical trials of
BLINCYTO®, CRS was reported in 15% of patients with R/R
ALL, in 7% of patients with MRD-positive ALL, and in 16% of
patients receiving BLINCYTO® cycles in the consolidation
phase of therapy. 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, including Immune
Effector Cell-Associated Neurotoxicity Syndrome:
BLINCYTO® can cause serious or life-threatening
neurologic toxicity, including ICANS. The incidence
of neurologic toxicities in clinical trials was approximately
65%. The median time to the first event was within the first 2
weeks of BLINCYTO® treatment. The most common
(≥ 10%) manifestations of neurological toxicity were headache and
tremor. Grade 3 or higher 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. The majority of neurologic toxicities resolved
following interruption of BLINCYTO®, but some resulted
in treatment discontinuation.
The incidence of signs and symptoms consistent with ICANS in
clinical trials was 7.5%. The onset of ICANS can be concurrent with
CRS, following resolution of CRS, or in the absence of CRS. There
is limited experience with BLINCYTO® in patients with
active ALL in the central nervous system (CNS) or a history of
neurologic events. Patients with a history or presence of
clinically relevant CNS pathology were excluded from clinical
studies. Patients with Down Syndrome over the age of 10 years may
have a higher risk of seizures with BLINCYTO®
therapy.
Monitor patients for signs and symptoms of neurological toxicities,
including ICANS, and interrupt or discontinue BLINCYTO®
as outlined in the PI. Advise outpatients to contact their
healthcare professional if they develop signs or symptoms of
neurological toxicities.
- 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 and ICANS,
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 total blood bilirubin 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 total bilirubin 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®.
- Benzyl Alcohol Toxicity in Neonates: Serious adverse
reactions, including fatal reactions and the "gasping syndrome,"
have been reported in very low birth weight (VLBW) neonates born
weighing less than 1500 g, and early preterm neonates (infants born
less than 34 weeks gestational age) who received intravenous drugs
containing benzyl alcohol as a preservative. Early preterm VLBW
neonates may be more likely to develop these reactions, because
they may be less able to metabolize benzyl alcohol.
Use the preservative-free preparations of
BLINCYTO® where possible in neonates. When
prescribing BLINCYTO® (with preservative) for
neonatal patients, consider the combined daily metabolic load of
benzyl alcohol from all sources including
BLINCYTO® (with preservative), other products
containing benzyl alcohol or other excipients (e.g., ethanol,
propylene glycol) which compete with benzyl alcohol for the same
metabolic pathway.
Monitor neonatal patients receiving BLINCYTO® (with
preservative) for new or worsening metabolic acidosis. The minimum
amount of benzyl alcohol at which serious adverse reactions may
occur in neonates is not known. The BLINCYTO® 7-Day
bag (with preservative) contains 7.4 mg of benzyl alcohol per
mL.
- Embryo-Fetal Toxicity: Based on its mechanism of action,
BLINCYTO® may cause fetal harm when administered to
a pregnant woman. Advise pregnant women of the potential risk to
the fetus. Advise females of reproductive potential to use
effective contraception during treatment with
BLINCYTO® and for 48 hours after the last
dose.
Adverse Reactions
- The safety of BLINCYTO® in adult and pediatric
patients one month and older with MRD-positive B-cell precursor ALL
(n=137), relapsed or refractory B-cell precursor ALL (n=267), and
Philadelphia chromosome-negative B
cell precursor ALL in consolidation (n=165) was evaluated in
clinical studies. The most common adverse reactions (≥ 20%)
to BLINCYTO® in this pooled population were
pyrexia, infusion-related reactions, headache, infection,
musculoskeletal pain, neutropenia, nausea, anemia,
thrombocytopenia, and diarrhea.
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 BLINCYTO® full Prescribing
Information, including BOXED
WARNINGS.
About BiTE® Technology
Bispecific T-cell
Engager (BiTE®) technology is a targeted immuno-oncology
platform that is designed to engage patient's 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 has a goal of leading 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
multiple 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. To learn more about
BiTE® technology, visit
https://www.amgenoncology.com/bite-platform.html.
About Amgen
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medicines to help millions of patients in their fight against some
of the world's toughest diseases. More than 40 years ago, Amgen
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and rare diseases.
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CONTACT: Amgen, Thousand Oaks
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Editor's note: Dr. Luger has received honoraria for an
Amgen-sponsored educational symposium.
- National Cancer Institute. Available
at: https://seer.cancer.gov/statfacts/html/alyl.html. Accessed
on February 8, 2024.
- Terwilliger T, et al. Blood Cancer J.
doi:10.1038/bcj.2017.53.
- Cancer.org. Available at:
https://www.cancer.org/cancer/types/acute-lymphocytic-leukemia/about/what-is-all.html
Accessed on February 8, 2024.
- Leukemia & Lymphoma Society. Available
at: https://www.lls.org/research/acute-lymphoblastic-leukemia-all#:~:text=B%2DALL%20is%20more%20common,about%2075%20percent%20of%20cases.
Accessed on February 8, 2024.
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