Summary of Prescribing Information
BLINCYTO® (blinatumomab)
for injection, for intravenous use
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. [See Dosage and Administration (2.3),
Warnings and Precautions (5.1)].
• Neurological toxicities, which may be severe, life-threatening, or fatal,
occurred in patients receiving BLINCYT O®. Interrupt or discontinue
BLINCYTO® as recommended. [See Dosage and Administration (2.3),
Warnings and Precautions (5.2)].
1. INDICATIONS AND USAGE
BLINCYTO® is indicated for the treatment of Philadelphia chromosome-negative relapsed
or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
This indication is approved under accelerated approval. Continued approval for this
indication may be contingent upon verification of clinical benefit in subsequent trials [see
Clinical Studies (14.1)].
4. CONTRAINDICATIONS
BLINCYTO® is contraindicated in patients with known hypersensitivity to blinatumomab
or to any component of the product formulation.
5. WARNINGS AND PRECAUTIONS
5.1 Cytokine Release Syndrome
Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in
patients receiving BLINCYTO®.
Infusion reactions have occurred with the BLINCYTO® infusion and may be clinically
indistinguishable from manifestations of CRS.
Serious adverse events that may be associated with CRS included pyrexia, headache,
nausea, asthenia, hypotension, increased alanine aminotransferase, increased aspartate
aminotransferase, and increased total bilirubin; these events infrequently led to
BLINCYTO® discontinuation. Life-threatening or fatal CRS was infrequently reported in
patients receiving BLINCYTO®. In some cases, disseminated intravascular coagulation
(DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/
macrophage activation syndrome (HLH/MAS) have been reported in the setting of CRS.
Patients should be closely monitored for signs or symptoms of these events.
Management of these events may require either temporary interruption or discontinuation
of BLINCYTO® [see Dosage and Administration (2.3)].
5.2 Neurological Toxicities
In patients receiving BLINCYTO® in clinical trials, neurological toxicities have occurred
in approximately 50% of patients. The median time to onset of any neurological toxicity
was 7 days. Grade 3 or higher (severe, life-threatening, or fatal) neurological toxicities
following initiation of BLINCYTO® administration occurred in approximately 15% of
patients and included encephalopathy, convulsions, speech disorders, disturbances in
consciousness, confusion and disorientation, and coordination and balance disorders.
The majority of events resolved following interruption of BLINCYTO®, but some resulted
in treatment discontinuation.
Monitor patients receiving BLINCYTO® for signs and symptoms of neurological
toxicities, and interrupt or discontinue BLINCYTO® as recommended [see Dosage and
Administration (2.3)].
5.3 Infections
In patients receiving BLINCYTO® in clinical trials, serious infections such as sepsis,
pneumonia, bacteremia, opportunistic infections, and catheter-site infections were
observed in approximately 25% of patients, some of which were life-threatening or
fatal. As appropriate, administer prophylactic antibiotics and employ surveillance testing
during treatment with BLINCYTO®. Monitor patients for signs and symptoms of infection
and treat appropriately.
5.4 Tumor Lysis Syndrome
Tumor lysis syndrome (TLS), which may be life-threatening or fatal, has been observed
in patients receiving BLINCYTO®. Appropriate prophylactic measures, including
pretreatment nontoxic cytoreduction and on-treatment hydration, should be used for
the prevention of TLS during BLINCYTO® treatment. Monitor for signs or symptoms
of TLS. Management of these events may require either temporary interruption or
discontinuation of BLINCYTO® [see Dosage and Administration (2.3)].
5.5 Neutropenia and Febrile Neutropenia
Neutropenia and febrile neutropenia, including life-threatening cases, have been
observed in patients receiving BLINCYTO®. Monitor laboratory parameters (including, but
not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO®
infusion. Interrupt BLINCYTO® if prolonged neutropenia occurs.
5.6 Effects on Ability to Drive and Use Machines
Due to the potential for neurologic events, including seizures, patients receiving
BLINCYTO® are at risk for loss of consciousness [see Warnings and Precautions (5.2)].
Advise patients to refrain from driving and engaging in hazardous occupations or
activities such as operating heavy or potentially dangerous machinery while BLINCYTO®
is being administered.
5.7 Elevated Liver Enzymes
Treatment with BLINCYTO® was associated with transient elevations in liver enzymes.
Although the majority of these events were observed in the setting of CRS, some
were observed outside of this setting. For these events, the median time to onset was
15 days. In patients receiving BLINCYTO® in clinical trials, Grade 3 or greater elevations
in liver enzymes occurred in approximately 6% of patients outside the setting of CRS and
resulted in treatment discontinuation in less than 1% of patients.
Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST),
gamma-glutamyl transferase (GGT), and total blood bilirubin prior to the start of
and during BLINCYTO® treatment. Interrupt BLINCYTO® if the transaminases rise
to greater than 5 times the upper limit of normal or if bilirubin rises to more than
3 times the upper limit of normal.
5.8 Leukoencephalopathy
Cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy
have been observed in patients receiving BLINCYTO®, especially in patients with prior
treatment with cranial irradiation and antileukemic chemotherapy (including systemic
high-dose methotrexate or intrathecal cytarabine). The clinical significance of these
imaging changes is unknown.
5.9 Preparation and Administration Errors
Preparation and administration errors have occurred with BLINCYTO® treatment. Follow
instructions for preparation (including admixing) and administration strictly to minimize
medication errors (including underdose and overdose) [see Dosage and Administration
(2.2) and (2.4)].
6. ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the label:
• Cytokine Release Syndrome [see Warnings and Precautions (5.1)]