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study, researchers tested two compounds (MI-463 and MI-503) in cell
lines and in mice with MLL leukemia.
The compounds blocked the MLL-menin interaction without harming normal
blood cells. Both compounds were delivered into the blood and metabolized
at a good rate.
Source: University of Michigan Health System press release; Borkin
D, He S, Miao H, et al. Pharmacologic inhibition of the menin-MLL
interaction blocks progression of MLL leukemia in vivo. Cancer Cell.
2015;27:589-602.
FDA Panel Votes in
Favor of Cangrelor for
Blood Clot Prevention
Cangrelor, a P2Y12 inhibitor under
investigation as an antiplatelet drug
for use during percutaneous coronary
interventions, was recently recommended for approval by the FDA’s Cardiovascular and Renal Drugs Advisory
Committee. The panel voted 9-2 (with
one abstention) in favor of a narrow
antithrombotic indication as an adjunct
to PCI for reducing risk of periprocedural ischemic complications. This
was a reversal from the 2-7 vote the
drug received recommending against
drug approval during an initial panel
meeting in February 2014. Panelists
who voted in favor of approval cited a
relatively small benefit with cangrelor
but also a smaller risk than clopido-
Summary of Prescribing Information
BLINCYTO™ (blinatumomab)
for injection, for intravenous use
WARNING: CYTOKINE RELEASE SYNDROME and
NEUROLOGICAL TOXICITIES
grel, another P2Y 12 inhibitor approved
for use during PCI. Several panelists
expressed concerns that cangrelor’s
approval could change practice by giving clinicians a convenient, although
no better and possibly less effective,
alternative to preloading. They called
for the FDA to reflect such concerns in
the label if it does follow their recommendation for approval.
Source: FDA Briefing Document
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
• Cytokine Release Syndrome (CRS), which may be lifethreatening 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, lifethreatening, or fatal, occurred in patients receiving
BLINCYTO™. Interrupt or discontinue BLINCYTO™ as
recommended. [See Dosage and Administration (2.3),
Warnings and Precautions (5.2)].
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 ontreatment 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)].
1.
Neutropenia and febrile neutropenia, including lifethreatening 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.
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
5.5 Neutropenia and Febrile Neutropenia
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.
• Effects on Ability to Drive and Use Machines [see
Warnings and Precautions (5.6)]
• Elevated Liver Enzymes [see Warnings and
Precautions (5.7)]
• Leukoencephalopathy [see Warnings and
Precautions (5.8)]
• Preparation and Administration Errors [see Warnings and
Precautions (5.9)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying
conditions, adverse reaction rates observed in the clinical
trials of a drug cannot be directly compared to rates in the
clinical trials of another drug and may not reflect the rates
observed in practice.
The safety data described in this section reflect exposure
to BLINCYTO™ in clinical trials in which 212 patients with
relapsed or refractory ALL received up to 28 mcg/day. All
patients received at least one dose of BLINCYTO™. The
median age of the study population was 37 years (range:
18 to 79 years), 63% were male, 79% were White, 3%
were Asian, and 3% were Black or African American.
The most common adverse reactions (≥ 20%) were pyrexia
(62%), headache (36%), peripheral edema (25%), febrile
neutropenia (25%), nausea (25%), hypokalemia (23%), and
constipation (20%).
5.1 Cytokine Release Syndrome
5.7 Elevated Liver Enzymes
Serious adverse reactions were reported in 65% of
patients. The most common serious adverse reactions
(≥ 2%) included febrile neutropenia, pyrexia, pneumonia,
sepsis, neutropenia, device-related infection, tremor,
encephalopathy,
infection,
overdose,
confusion,
Staphylococcal bacteremia, and headache.
Cytokine Release Syndrome (CRS), which may be lifethreatening or fatal, occurred in patients receiving
BLINCYTO™.
Treatment with BLINCYTO™ was associated with transient
elevations in liver V秖