ASH News Daily 2017 - Issue 3 - C-17

IMPORTANT SAFETY INFORMATION (continued)
CYTOKINE RELEASE SYNDROME (CRS)
CRS, including fatal or life-threatening reactions, occurred following treatment
with YESCARTA™. In Study 1, CRS occurred in 94% (101/108) of patients receiving
YESCARTA™, including ≥ Grade 3 (Lee grading system) CRS in 13% (14/108) of
patients. Among patients who died after receiving YESCARTA™, four had ongoing
CRS events at the time of death. The median time to onset was 2 days (range:
1 to 12 days) and the median duration of CRS was 7 days (range: 2 to 58 days).
Key manifestations of CRS 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 (HLH/MAS) [see Adverse Reactions (6)].
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 [see
Patient Counseling Information (17)]. At the first sign of CRS, institute treatment
with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated
[see Dosage and Administration (2.3)].
NEUROLOGIC TOXICITIES
Neurologic toxicities, that were fatal or life-threatening, occurred following
treatment with YESCARTA™. Neurologic toxicities occurred in 87% of patients.
Ninety-eight percent of all neurologic toxicities occurred within the first 8 weeks
of YESCARTA™ infusion, with a median time to onset of 4 days (range: 1 to 43
days). The median duration of neurologic toxicities was 17 days. Grade 3 or higher
neurologic toxicities 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 [see Management of Severe Adverse Reactions (2.3); Neurologic
Toxicities].
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 [see Boxed Warning and Warnings
and Precautions (5.1 and 5.2)]. 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 two 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 with the infusion of YESCARTA™. 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 in patients after YESCARTA™ infusion.
In Study 1, infections (all grades) occurred in 38% of patients. Grade 3 or higher
infections occurred in 23% of patients. 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 antimicrobials according to local guidelines.
Febrile neutropenia was observed in 36% of patients after YESCARTA™ infusion
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.
Viral Reactivation
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.
PROLONGED CYTOPENIAS
Patients may exhibit cytopenias for several weeks following lymphodepleting
chemotherapy and YESCARTA™ infusion. In Study 1, 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 in patients receiving
treatment with YESCARTA™. In Study 1, hypogammaglobulinemia occurred in 15%
of patients. Monitor immunoglobulin levels after treatment with YESCARTA™ 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 with YESCARTA™.
SECONDARY MALIGNANCIES
Patients treated with YESCARTA™ 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 receiving YESCARTA™ 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.
Serious adverse reactions occurred in 52% of patients. The most common serious
adverse reactions (> 2%) include encephalopathy, fever, lung infection, febrile
neutropenia, cardiac arrhythmia, cardiac failure, urinary tract infection, renal
insufficiency, aphasia, cardiac arrest, Clostridium difficile infection, delirium,
hypotension, and hypoxia.
The most common (≥ 10%) Grade 3 or higher reactions include febrile
neutropenia, fever, CRS, encephalopathy, infections-pathogen unspecified,
hypotension, hypoxia, and lung infections.

Please see Brief Summary of Prescribing Information, including BOXED WARNING,
on adjacent pages.
Visit YESCARTAhcp.com

Santa Monica, CA

11/3/17 4:21 PM



Table of Contents for the Digital Edition of ASH News Daily 2017 - Issue 3

ASH News Daily 2017 - Issue 3 - A-1
ASH News Daily 2017 - Issue 3 - A-2
ASH News Daily 2017 - Issue 3 - A-3
ASH News Daily 2017 - Issue 3 - A-4
ASH News Daily 2017 - Issue 3 - A-5
ASH News Daily 2017 - Issue 3 - A-6
ASH News Daily 2017 - Issue 3 - A-7
ASH News Daily 2017 - Issue 3 - A-8
ASH News Daily 2017 - Issue 3 - A-9
ASH News Daily 2017 - Issue 3 - A-10
ASH News Daily 2017 - Issue 3 - A-11
ASH News Daily 2017 - Issue 3 - A-12
ASH News Daily 2017 - Issue 3 - A-13
ASH News Daily 2017 - Issue 3 - A-14
ASH News Daily 2017 - Issue 3 - A-15
ASH News Daily 2017 - Issue 3 - A-16
ASH News Daily 2017 - Issue 3 - A-17
ASH News Daily 2017 - Issue 3 - A-18
ASH News Daily 2017 - Issue 3 - A-19
ASH News Daily 2017 - Issue 3 - A-20
ASH News Daily 2017 - Issue 3 - A-21
ASH News Daily 2017 - Issue 3 - A-22
ASH News Daily 2017 - Issue 3 - A-23
ASH News Daily 2017 - Issue 3 - A-24
ASH News Daily 2017 - Issue 3 - A-25
ASH News Daily 2017 - Issue 3 - A-26
ASH News Daily 2017 - Issue 3 - A-27
ASH News Daily 2017 - Issue 3 - A-28
ASH News Daily 2017 - Issue 3 - B-1
ASH News Daily 2017 - Issue 3 - B-2
ASH News Daily 2017 - Issue 3 - B-3
ASH News Daily 2017 - Issue 3 - B-4
ASH News Daily 2017 - Issue 3 - B-5
ASH News Daily 2017 - Issue 3 - B-6
ASH News Daily 2017 - Issue 3 - B-7
ASH News Daily 2017 - Issue 3 - B-8
ASH News Daily 2017 - Issue 3 - B-9
ASH News Daily 2017 - Issue 3 - B-10
ASH News Daily 2017 - Issue 3 - B-11
ASH News Daily 2017 - Issue 3 - B-12
ASH News Daily 2017 - Issue 3 - B-13
ASH News Daily 2017 - Issue 3 - B-14
ASH News Daily 2017 - Issue 3 - B-15
ASH News Daily 2017 - Issue 3 - B-16
ASH News Daily 2017 - Issue 3 - B-17
ASH News Daily 2017 - Issue 3 - B-18
ASH News Daily 2017 - Issue 3 - B-19
ASH News Daily 2017 - Issue 3 - B-20
ASH News Daily 2017 - Issue 3 - B-21
ASH News Daily 2017 - Issue 3 - B-22
ASH News Daily 2017 - Issue 3 - B-23
ASH News Daily 2017 - Issue 3 - B-24
ASH News Daily 2017 - Issue 3 - B-25
ASH News Daily 2017 - Issue 3 - B-26
ASH News Daily 2017 - Issue 3 - B-27
ASH News Daily 2017 - Issue 3 - B-30
ASH News Daily 2017 - Issue 3 - B-31
ASH News Daily 2017 - Issue 3 - B-32
ASH News Daily 2017 - Issue 3 - B-33
ASH News Daily 2017 - Issue 3 - B-34
ASH News Daily 2017 - Issue 3 - B-35
ASH News Daily 2017 - Issue 3 - B-36
ASH News Daily 2017 - Issue 3 - B-37
ASH News Daily 2017 - Issue 3 - B-38
ASH News Daily 2017 - Issue 3 - B-39
ASH News Daily 2017 - Issue 3 - B-40
ASH News Daily 2017 - Issue 3 - B-41
ASH News Daily 2017 - Issue 3 - B-42
ASH News Daily 2017 - Issue 3 - B-43
ASH News Daily 2017 - Issue 3 - B-44
ASH News Daily 2017 - Issue 3 - B-45
ASH News Daily 2017 - Issue 3 - B-46
ASH News Daily 2017 - Issue 3 - B-47
ASH News Daily 2017 - Issue 3 - B-48
ASH News Daily 2017 - Issue 3 - B-49
ASH News Daily 2017 - Issue 3 - B-50
ASH News Daily 2017 - Issue 3 - B-51
ASH News Daily 2017 - Issue 3 - B-52
ASH News Daily 2017 - Issue 3 - B-53
ASH News Daily 2017 - Issue 3 - B-54
ASH News Daily 2017 - Issue 3 - B-55
ASH News Daily 2017 - Issue 3 - B-56
ASH News Daily 2017 - Issue 3 - C-1
ASH News Daily 2017 - Issue 3 - C-2
ASH News Daily 2017 - Issue 3 - C-3
ASH News Daily 2017 - Issue 3 - C-4
ASH News Daily 2017 - Issue 3 - C-5
ASH News Daily 2017 - Issue 3 - C-6
ASH News Daily 2017 - Issue 3 - C-7
ASH News Daily 2017 - Issue 3 - C-8
ASH News Daily 2017 - Issue 3 - C-9
ASH News Daily 2017 - Issue 3 - C-10
ASH News Daily 2017 - Issue 3 - C-11
ASH News Daily 2017 - Issue 3 - C-12
ASH News Daily 2017 - Issue 3 - C-13
ASH News Daily 2017 - Issue 3 - C-14
ASH News Daily 2017 - Issue 3 - C-15
ASH News Daily 2017 - Issue 3 - C-16
ASH News Daily 2017 - Issue 3 - C-17
ASH News Daily 2017 - Issue 3 - C-18
ASH News Daily 2017 - Issue 3 - C-19
ASH News Daily 2017 - Issue 3 - C-20
ASH News Daily 2017 - Issue 3 - C-21
ASH News Daily 2017 - Issue 3 - C-22
ASH News Daily 2017 - Issue 3 - C-23
ASH News Daily 2017 - Issue 3 - C-24
ASH News Daily 2017 - Issue 3 - C-25
ASH News Daily 2017 - Issue 3 - C-26
ASH News Daily 2017 - Issue 3 - C-27
ASH News Daily 2017 - Issue 3 - C-28
ASH News Daily 2017 - Issue 3 - C-29
ASH News Daily 2017 - Issue 3 - C-30
ASH News Daily 2017 - Issue 3 - C-31
ASH News Daily 2017 - Issue 3 - C-32
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