IMPORTANT SAFETY INFORMATION
(continued)
CYTOKINE RELEASE SYNDROME (CRS): CRS
occurred in 94% of patients, including 13% with
≥ Grade 3. Among patients who died after receiving
YESCARTA ® , 4 had ongoing CRS at death.
The median time to onset was 2 days (range:
1-12 days) and median duration was 7 days (range:
2-58 days). Key manifestations include fever (78%),
hypotension (41%), tachycardia (28%), hypoxia
(22%), and chills (20%). Serious events that may be
associated with CRS include cardiac arrhythmias
(including atrial fibrillation and ventricular
tachycardia), cardiac arrest, cardiac failure,
renal insufficiency, capillary leak syndrome,
hypotension, hypoxia, and hemophagocytic
lymphohistiocytosis/macrophage activation
syndrome. Ensure that 2 doses of tocilizumab are
available prior to infusion of YESCARTA ® . Monitor
patients at least daily for 7 days at the certified
healthcare facility following infusion for signs
and symptoms of CRS. Monitor patients for signs
or symptoms of CRS for 4 weeks after infusion.
Counsel patients to seek immediate medical
attention should signs or symptoms of CRS occur
at any time. At the first sign of CRS, institute
treatment with supportive care, tocilizumab or
tocilizumab and corticosteroids as indicated.
NEUROLOGIC TOXICITIES: Neurologic toxicities
occurred in 87% of patients. Ninety-eight percent
of all neurologic toxicities occurred within the first
8 weeks, with a median time to onset of 4 days
(range: 1-43 days) and a median duration of
17 days. Grade 3 or higher occurred in 31% of
patients. The most common neurologic toxicities
included encephalopathy (57%), headache
(44%), tremor (31%), dizziness (21%), aphasia
(18%), delirium (17%), insomnia (9%) and anxiety
(9%). Prolonged encephalopathy lasting up to
173 days was noted. Serious events including
leukoencephalopathy and seizures occurred with
YESCARTA ® . Fatal and serious cases of cerebral
edema have occurred in patients treated with
YESCARTA ® . Monitor patients at least daily for
7 days at the certified healthcare facility following
infusion for signs and symptoms of neurologic
toxicities. Monitor patients for signs or symptoms
of neurologic toxicities for 4 weeks after infusion
and treat promptly.
YESCARTA ® REMS: Because of the risk of CRS
and neurologic toxicities, YESCARTA ® is available
only through a restricted program under a Risk
Evaluation and Mitigation Strategy (REMS) called
the YESCARTA ® REMS. The required components
of the YESCARTA ® REMS are: Healthcare facilities
that dispense and administer YESCARTA ® must be
enrolled and comply with the REMS requirements.
Certified healthcare facilities must have on-site,
immediate access to tocilizumab, and ensure that
a minimum of 2 doses of tocilizumab are available
for each patient for infusion within 2 hours after
YESCARTA ® infusion, if needed for treatment of
CRS. Certified healthcare facilities must ensure
that healthcare providers who prescribe, dispense
or administer YESCARTA ® are trained about the
management of CRS and neurologic toxicities.
Further information is available at
www.YESCARTAREMS.com or
1-844-454-KITE (5483).
HYPERSENSITIVITY REACTIONS: Allergic
reactions may occur. Serious hypersensitivity
reactions including anaphylaxis may be due to
dimethyl sulfoxide (DMSO) or residual gentamicin
in YESCARTA ® .
SERIOUS INFECTIONS: Severe or life-threatening
infections occurred. Infections (all grades)
occurred in 38% of patients, and in 23% with
≥ Grade 3. Grade 3 or higher infections with an
unspecified pathogen occurred in 16% of patients,
bacterial infections in 9%, and viral infections
in 4%. YESCARTA ® should not be administered
to patients with clinically significant active
systemic infections. Monitor patients for signs
and symptoms of infection before and after
YESCARTA ® infusion and treat appropriately.
Administer prophylactic anti-microbials
according to local guidelines. Febrile neutropenia
was observed in 36% of patients and may be
concurrent with CRS. In the event of febrile
neutropenia, evaluate for infection and manage
with broad spectrum antibiotics, fluids and other
supportive care as medically indicated. Hepatitis B
virus (HBV) reactivation, in some cases resulting
in fulminant hepatitis, hepatic failure and death,
can occur in patients treated with drugs directed
against B cells. Perform screening for HBV, HCV,
and HIV in accordance with clinical guidelines
before collection of cells for manufacturing.
Reference: 1. YESCARTA ™ [package insert]. Santa Monica, CA: Kite Pharma; 2017.
PROLONGED CYTOPENIAS: Patients may
exhibit cytopenias for several weeks following
lymphodepleting chemotherapy and YESCARTA ®
infusion. Grade 3 or higher cytopenias not resolved
by Day 30 following YESCARTA ® infusion occurred
in 28% of patients and included thrombocytopenia
(18%), neutropenia (15%), and anemia (3%).
Monitor blood counts after YESCARTA ® infusion.
HYPOGAMMAGLOBULINEMIA: B-cell aplasia
and hypogammaglobulinemia can occur.
Hypogammaglobulinemia occurred in 15%
of patients. Monitor immunoglobulin levels
after treatment and manage using infection
precautions, antibiotic prophylaxis and
immunoglobulin replacement. The safety of
immunization with live viral vaccines during or
following YESCARTA ® treatment has not been
studied. Vaccination with live virus vaccines is not
recommended for at least 6 weeks prior to the
start of lymphodepleting chemotherapy, during
YESCARTA ® treatment, and until immune recovery
following treatment.
SECONDARY MALIGNANCIES: Patients may
develop secondary malignancies. Monitor life-
long for secondary malignancies. In the event that
a secondary malignancy occurs, contact Kite at
1-844-454-KITE (5483) to obtain instructions on
patient samples to collect for testing.
EFFECTS ON ABILITY TO DRIVE AND USE
MACHINES: Due to the potential for neurologic
events, including altered mental status or
seizures, patients are at risk for altered or
decreased consciousness or coordination in the
8 weeks following YESCARTA ® infusion. Advise
patients to refrain from driving and engaging
in hazardous occupations or activities, such
as operating heavy or potentially dangerous
machinery, during this initial period.
ADVERSE REACTIONS: The most common
adverse reactions (incidence ≥ 20%) include CRS,
fever, hypotension, encephalopathy, tachycardia,
fatigue, headache, decreased appetite, chills,
diarrhea, febrile neutropenia, infections-pathogen
unspecified, nausea, hypoxia, tremor, cough,
vomiting, dizziness, constipation, and cardiac
arrhythmias.
Please see Brief Summary of Prescribing
Information, including BOXED WARNING,
on the following pages.
Santa Monica, CA