HIGHLIGHTS OF PRESCRIBING INFORMATION -------------------DOSAGE FORMS AND STRENGTHS------------------------

These highlights do not include all the information needed to use • YESCARTA is available as a cell suspension for infusion.
YESCARTA safely and effectively. See full prescribing information for • YESCARTA comprises a suspension of 2 × 106 CAR-positive viable T
YESCARTA. cells per kg of body weight, with a maximum of 2 × 108 CAR-positive
viable T cells in approximately 68 mL. (3)
YESCARTA® (axicabtagene ciloleucel) suspension for intravenous
infusion ----------------------------CONTRAINDICATIONS---------------------------------
Initial U.S. Approval: October 2017 • None. (4)

------------------------WARNINGS AND PRECAUTIONS-----------------------

WARNING: CYTOKINE RELEASE SYNDROME AND • Hypersensitivity Reactions: Monitor for hypersensitivity reactions during
NEUROLOGIC TOXICITIES infusion. (5.4)
See full prescribing information for complete boxed warning. • Serious Infections: Monitor patients for signs and symptoms of infection;
treat appropriately. (5.5)
• Cytokine Release Syndrome (CRS), including fatal or life- • Prolonged Cytopenias: Patients may exhibit Grade 3 or higher cytopenias
threatening reactions, occurred in patients receiving YESCARTA. for several weeks following YESCARTA infusion. Monitor complete
Do not administer YESCARTA to patients with active infection or blood counts. (5.6)
inflammatory disorders. Treat severe or life-threatening CRS with • Hypogammaglobulinemia: Monitor and provide replacement therapy. (5.7)
tocilizumab or tocilizumab and corticosteroids (2.2, 2.3, 5.1). • Secondary Malignancies: In the event that a secondary malignancy occurs
• Neurologic toxicities, including fatal or life-threatening reactions, after treatment with YESCARTA, contact Kite at 1-844-454-KITE (5483).
occurred in patients receiving YESCARTA, including (5.8)
concurrently with CRS or after CRS resolution. Monitor for • Effects on Ability to Drive and Use Machines: Advise patients to refrain
neurologic toxicities after treatment with YESCARTA. Provide from driving and engaging in hazardous occupations or activities, such as
supportive care and/or corticosteroids, as needed (2.2, 2.3, 5.2). operating heavy or potentially dangerous machinery, for at least 8 weeks
• YESCARTA is available only through a restricted program under after receiving YESCARTA. (5.9)
a Risk Evaluation and Mitigation Strategy (REMS) called the
YESCARTA REMS (5.3). ------------------------------ADVERSE REACTIONS-------------------------------
The most common non-laboratory adverse reactions (incidence greater than or
equal to 20%) are: cytokine release syndrome, fever, hypotension,
-----------------------------INDICATIONS AND USAGE-------------------------- encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills,
YESCARTA is a CD19-directed genetically modified autologous T cell diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea,
immunotherapy indicated for the treatment of adult patients with relapsed or hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac
refractory large B-cell lymphoma after two or more lines of systemic therapy, arrhythmias (5.4, 6.1).
including diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and To report SUSPECTED ADVERSE REACTIONS, contact Kite at 1-844-
DLBCL arising from follicular lymphoma. 454-KITE (5483) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Limitation of Use: YESCARTA is not indicated for the treatment of patients See 17 for PATIENT COUNSELING INFORMATION and Medication
with primary central nervous system lymphoma (1). Guide.

--------------------------DOSAGE AND ADMINISTRATION--------------------

For autologous use only. For intravenous use only. Revised: 05/2020
• Do NOT use a leukodepleting filter.
• Administer a lymphodepleting regimen of cyclophosphamide and
fludarabine before infusion of YESCARTA. (2.2)
• Verify the patient’s identity prior to infusion. (2.2)
• Premedicate with acetaminophen and an H1-antihistamine. (2.2)
• Confirm availability of tocilizumab prior to infusion. (2.1, 5.1)
• Dosing of YESCARTA is based on the number of chimeric antigen
receptor (CAR)-positive viable T cells. (2.1)
• The target YESCARTA dose is 2 × 106 CAR-positive viable T cells per
kg body weight, with a maximum of 2 × 108 CAR-positive viable T cells.
(2.1)
Administer YESCARTA in a certified healthcare facility. (2.2, 5.1, 5.2, 5.3)
FULL PRESCRIBING INFORMATION: CONTENTS* 6.1 Clinical Trials Experience
6.2 Immunogenicity
WARNING: CYTOKINE RELEASE SYNDROME AND 6.3 Postmarketing Experience
NEUROLOGIC TOXICITIES 8 USE IN SPECIFIC POPULATIONS
1 INDICATIONS AND USAGE 8.1 Pregnancy
2 DOSAGE AND ADMINISTRATION 8.2 Lactation
2.1 Dose 8.3 Females and Males of Reproductive Potential
2.2 Administration 8.4 Pediatric Use
2.3 Management of Severe Adverse Reactions 8.5 Geriatric Use
3 DOSAGE FORMS AND STRENGTHS 11 DESCRIPTION
4 CONTRAINDICATIONS 12 CLINICAL PHARMACOLOGY
5 WARNINGS AND PRECAUTIONS 12.1 Mechanism of Action
5.1 Cytokine Release Syndrome 12.2 Pharmacodynamics
5.2 Neurologic Toxicities 12.3 Pharmacokinetics
5.3 YESCARTA REMS 13 NONCLINICAL TOXICOLOGY
5.4 Hypersensitivity Reactions 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
5.5 Serious Infections 14 CLINICAL STUDIES
5.6 Prolonged Cytopenias 15 REFERENCES
5.7 Hypogammaglobulinemia 16 HOW SUPPLIED/STORAGE AND HANDLING
5.8 Secondary Malignancies 17 PATIENT COUNSELING INFORMATION
5.9 Effects on Ability to Drive and Use Machines * Sections or subsections omitted from the full prescribing information are
6 ADVERSE REACTIONS not listed.
FULL PRESCRIBING INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

• Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients
receiving YESCARTA. Do not administer YESCARTA to patients with active infection or inflammatory
disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids [see
Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].
• Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving
YESCARTA, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities
after treatment with YESCARTA. Provide supportive care and/or corticosteroids as needed [see Dosage
and Administration (2.2, 2.3), Warnings and Precautions (5.2)].
• YESCARTA is available only through a restricted program under a Risk Evaluation and Mitigation
Strategy (REMS) called the YESCARTA REMS [see Warnings and Precautions (5.3)].

1 INDICATIONS AND USAGE

YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of
adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including
diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high
grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
Limitation of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system
lymphoma.
2 DOSAGE AND ADMINISTRATION
For autologous use only. For intravenous use only.
2.1 Dose
Each single infusion bag of YESCARTA contains a suspension of chimeric antigen receptor (CAR)-positive T cells in
approximately 68 mL. The target dose is 2 × 106 CAR-positive viable T cells per kg body weight, with a maximum of
2 × 108 CAR-positive viable T cells.
2.2 Administration
YESCARTA is for autologous use only. The patient’s identity must match the patient identifiers on the YESCARTA
cassette and infusion bag. Do not infuse YESCARTA if the information on the patient-specific label does not match
the intended patient.
Preparing Patient for YESCARTA Infusion
Confirm availability of YESCARTA prior to starting the lymphodepleting regimen.
Pre-treatment
• Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m2 intravenously and
fludarabine 30 mg/m2 intravenously on the fifth, fourth, and third day before infusion of YESCARTA.
Premedication
• Administer acetaminophen 650 mg PO and diphenhydramine 12.5 mg intravenously or PO approximately 1
hour before YESCARTA infusion.
• Avoid prophylactic use of systemic corticosteroids, as it may interfere with the activity of YESCARTA.
Preparation of YESCARTA for Infusion
Coordinate the timing of YESCARTA thaw and infusion. Confirm the infusion time in advance, and adjust the start
time of YESCARTA thaw such that it will be available for infusion when the patient is ready.
• Confirm patient identity: Prior to YESCARTA preparation, match the patient’s identity with the patient
identifiers on the YESCARTA cassette.
• Do not remove the YESCARTA product bag from the cassette if the information on the patient-specific label
does not match the intended patient.
• Once patient identification is confirmed, remove the YESCARTA product bag from the cassette and check
that the patient information on the cassette label matches the bag label.
• Inspect the product bag for any breaches of container integrity such as breaks or cracks before thawing. If the
bag is compromised, follow the local guidelines (or call Kite at 1-844-454-KITE).
• Place the infusion bag inside a second sterile bag per local guidelines.
• Thaw YESCARTA at approximately 37°C using either a water bath or dry thaw method until there is no
visible ice in the infusion bag. Gently mix the contents of the bag to disperse clumps of cellular material. If
visible cell clumps remain continue to gently mix the contents of the bag. Small clumps of cellular material
should disperse with gentle manual mixing. Do not wash, spin down, and/or re-suspend YESCARTA in new
media prior to infusion.
• Once thawed, YESCARTA may be stored at room temperature (20°C to 25°C) for up to 3 hours.
Administration
• For autologous use only.
• Ensure that tocilizumab and emergency equipment are available prior to infusion and during the recovery
period.
• Do NOT use a leukodepleting filter.
• Central venous access is recommended for the infusion of YESCARTA.
• Confirm the patient’s identity matches the patient identifiers on the YESCARTA product bag.
• Prime the tubing with normal saline prior to infusion.
• Infuse the entire contents of the YESCARTA bag within 30 minutes by either gravity or a peristaltic pump.
YESCARTA is stable at room temperature for up to 3 hours after thaw.
• Gently agitate the product bag during YESCARTA infusion to prevent cell clumping.
• After the entire content of the product bag is infused, rinse the tubing with normal saline at the same infusion
rate to ensure all product is delivered.
YESCARTA contains human blood cells that are genetically modified with replication incompetent retroviral vector.
Follow universal precautions and local biosafety guidelines for handling and disposal to avoid potential transmission
of infectious diseases.
Monitoring
• Administer YESCARTA at a certified healthcare facility.
• Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and
symptoms of CRS and neurologic toxicities.
• Instruct patients to remain within proximity of the certified healthcare facility for at least 4 weeks following
infusion.
2.3 Management of Severe Adverse Reactions
Cytokine Release Syndrome
Identify CRS based on clinical presentation [see Warnings and Precautions (5.1)]. Evaluate for and treat other causes
of fever, hypoxia, and hypotension. If CRS is suspected, manage according to the recommendations in Table 1.
Patients who experience Grade 2 or higher CRS (e.g., hypotension, not responsive to fluids, or hypoxia requiring
supplemental oxygenation) should be monitored with continuous cardiac telemetry and pulse oximetry. For patients
experiencing severe CRS, consider performing an echocardiogram to assess cardiac function. For severe or life-
threatening CRS, consider intensive-care supportive therapy.
Table 1. CRS Grading and Management Guidance

CRS Grade a Tocilizumab Corticosteroids

Grade 1 N/A N/A

Symptoms require symptomatic
treatment only (e.g., fever, nausea,
fatigue, headache, myalgia, malaise).

Grade 2 Administer tocilizumab c 8 mg/kg Manage per Grade 3 if no improvement

intravenously over 1 hour (not to within 24 hours after starting
Symptoms require and respond to
exceed 800 mg). tocilizumab.
moderate intervention.
If no clinical improvement in the signs
Oxygen requirement less than 40%
and symptoms of CRS after the first
FiO2 or hypotension responsive to
dose, repeat tocilizumab every 8 hours
fluids or low-dose of one vasopressor or
as needed.
Grade 2 organ toxicity.b
Limit to a maximum of 3 doses in a 24-
hour period; maximum total of 4 doses.

Grade 3 Per Grade 2 Administer methylprednisolone

1 mg/kg intravenously twice daily or
Symptoms require and respond to
equivalent dexamethasone (e.g., 10 mg
aggressive intervention.
intravenously every 6 hours).
Oxygen requirement greater than or
Continue corticosteroids use until the
equal to 40% FiO2 or hypotension
event is Grade 1 or less, then taper over
requiring high-dose or multiple
3 days.
vasopressors or
Grade 3 organ toxicity or Grade 4
transaminitis.

Grade 4 Per Grade 2 Administer methylprednisolone 1000

mg intravenously per day for 3 days; if
Life-threatening symptoms.
improves, then manage as above.
Requirements for ventilator support,
continuous veno-venous hemodialysis
(CVVHD) or
Grade 4 organ toxicity (excluding
transaminitis).
a. Lee et al. 2014.
b. Refer to Table 2 for management of neurologic toxicity.
c. Refer to tocilizumab Prescribing Information for details.

Neurologic Toxicity
Monitor patients for signs and symptoms of neurologic toxicities (Table 2). Rule out other causes of neurologic
symptoms. Patients who experience Grade 2 or higher neurologic toxicities should be monitored with continuous
cardiac telemetry and pulse oximetry. Provide intensive-care supportive therapy for severe or life-threatening
neurologic toxicities. Consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis for
any Grade 2 or higher neurologic toxicities.
Table 2. Neurologic Toxicity Grading and Management Guidance
Grading
Concurrent CRS No Concurrent CRS
Assessment

Grade 2 Administer tocilizumab per Table 1 for Administer dexamethasone 10 mg intravenously

management of Grade 2 CRS. every 6 hours.
If no improvement within 24 hours after starting Continue dexamethasone use until the event is
tocilizumab, administer dexamethasone 10 mg Grade 1 or less, then taper over 3 days.
intravenously every 6 hours if not already taking
other corticosteroids. Continue dexamethasone
use until the event is Grade 1 or less, then taper
over 3 days.

Consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.

Grade 3 Administer tocilizumab per Table 1 for Administer dexamethasone 10 mg intravenously

management of Grade 2 CRS. every 6 hours.
In addition, administer dexamethasone 10 mg Continue dexamethasone use until the event is
intravenously with the first dose of tocilizumab Grade 1 or less, then taper over 3 days.
and repeat dose every 6 hours. Continue
dexamethasone use until the event is Grade 1 or
less, then taper over 3 days.

Consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.

Grade 4 Administer tocilizumab per Table 1 for Administer methylprednisolone 1000 mg

management of Grade 2 CRS. intravenously per day for 3 days; if improves, then
manage as above.
Administer methylprednisolone 1000 mg
intravenously per day with first dose of
tocilizumab and continue methylprednisolone
1000 mg intravenously per day for 2 more days; if
improves, then manage as above.

Consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.

3 DOSAGE FORMS AND STRENGTHS

YESCARTA is available as a cell suspension for infusion.
A single dose of YESCARTA contains 2 × 106 CAR-positive viable T cells per kg of body weight (or maximum of
2 × 108 CAR-positive viable T cells for patients 100 kg and above) in approximately 68 mL suspension in an infusion
bag [see How Supplied/Storage and Handling (16)].
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Cytokine Release Syndrome
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 system1) 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)].
5.2 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 Dosage and Administration (2.3)].
5.3 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 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).
5.4 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.
5.5 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.
5.6 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.
5.7 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.
5.8 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.
5.9 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.
6 ADVERSE REACTIONS
The following adverse reactions are described elsewhere in the labeling:
• Cytokine Release Syndrome [see Warnings and Precautions (5.1, 5.3)]
• Neurologic Toxicities [see Warnings and Precautions (5.2, 5.3)]
• Hypersensitivity Reactions [see Warnings and Precautions (5.4)]
• Serious Infections [see Warnings and Precautions (5.5)]
• Prolonged Cytopenias [see Warnings and Precautions (5.6)]
• Hypogammaglobulinemia [see Warnings and Precautions (5.7)]
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 YESCARTA in the clinical trial (Study 1) in which 108
patients with relapsed/refractory B-cell NHL received CAR-positive T cells based on a recommended dose which was
weight-based [see Clinical Studies (14)]. Patients with a history of CNS disorders (such as seizures or cerebrovascular
ischemia) or autoimmune disease requiring systemic immunosuppression were ineligible. The median duration of
follow-up was 8.7 months. The median age of the study population was 58 years (range: 23 to 76 years); 68% were
male. The baseline ECOG performance status was 43% with ECOG 0, and 57% with ECOG 1.
The most common adverse reactions (incidence ≥ 20%) included 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%) included
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 included febrile neutropenia, fever, CRS, encephalopathy,
infections-pathogen unspecified, hypotension, hypoxia, and lung infections.
Forty-five percent (49/108) of patients received tocilizumab after infusion of YESCARTA.
Table 3 summarizes the adverse reactions that occurred in at least 10% of patients treated with YESCARTA and
Table 4 describes the laboratory abnormalities of Grade 3 or 4 that occurred in at least 10% of patients.
Table 3. Summary of Adverse Reactions Observed in at Least 10% of Patients Treated with YESCARTA
in Study 1
Adverse Reaction Any Grade (%) Grade 3 or Higher (%)
Blood and Lymphatic System Disorders
Febrile neutropenia 34 31
Cardiac Disorders
Tachycardia a 57 2
Arrhythmia b 23 7
Gastrointestinal Disorders
Diarrhea 38 4
Nausea 34 0
Vomiting 26 1
Constipation 23 0
Abdominal pain c 14 1
Dry mouth 11 0
General Disorders and Administration Site Conditions
Fever d 86 16
Fatigue e 46 3
Chills 40 0
Edema f 19 1
Immune System Disorders
Cytokine release syndrome 94 13
Hypogammaglobulinemia g 15 0
Infections and Infestations
Infections-pathogen unspecified 26 16
Viral infections 16 4
Bacterial infections 13 9
Investigations
Decreased appetite 44 2
Weight decreased 16 0
Dehydration 11 3
Musculoskeletal and Connective Tissue Disorders
Motor dysfunction h 19 1
Pain in extremity i 17 2
Back pain 15 1
Muscle pain 14 1
Arthralgia 10 0
Nervous System Disorders
Encephalopathy j 57 29
Headache k 45 1
Adverse Reaction Any Grade (%) Grade 3 or Higher (%)
Tremor 31 2
Dizziness l 21 1
Aphasia m 18 6
Psychiatric Disorders
Delirium n 17 6
Respiratory, Thoracic and Mediastinal Disorders
Hypoxia o 32 11
Cough p 30 0
Dyspnea q 19 3
Pleural effusion 13 2
Renal and Urinary Disorders
Renal insufficiency 12 5
Vascular Disorders
Hypotension r 57 15
Hypertension 15 6
Thrombosis s 10 1
The following events were also counted in the incidence of CRS: tachycardia, arrhythmia, fever, chills, hypoxia, renal insufficiency, and
hypotension.
a. Tachycardia includes tachycardia, sinus tachycardia.
b. Arrhythmia includes arrhythmia, atrial fibrillation, atrial flutter, atrioventricular block, bundle branch block right, electrocardiogram QT
prolonged, extra-systoles, heart rate irregular, supraventricular extra systoles, supraventricular tachycardia, ventricular arrhythmia,
ventricular tachycardia.
c. Abdominal pain includes abdominal pain, abdominal pain lower, abdominal pain upper.
d. Fever includes fever, febrile neutropenia.
e. Fatigue includes fatigue, malaise.
f. Edema includes face edema, generalized edema, local swelling, localized edema, edema, edema genital, edema peripheral, periorbital
edema, peripheral swelling, scrotal edema.
g. Hypogammaglobulinemia includes hypogammaglobulinemia, blood immunoglobulin D decreased, blood immunoglobulin G decreased.
h. Motor dysfunction includes muscle spasms, muscular weakness.
i. Pain in extremity includes pain not otherwise specified, pain in extremity.
j. Encephalopathy includes cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, encephalopathy,
hypersomnia, leukoencephalopathy, memory impairment, mental status changes, paranoia, somnolence, stupor.
k. Headache includes headache, head discomfort, sinus headache, procedural headache.
l. Dizziness includes dizziness, presyncope, syncope.
m. Aphasia includes aphasia, dysphasia.
n. Delirium includes agitation, delirium, delusion, disorientation, hallucination, hyperactivity, irritability, restlessness.
o. Hypoxia includes hypoxia, oxygen saturation decreased.
p. Cough includes cough, productive cough, upper-airway cough syndrome.
q. Dyspnea includes acute respiratory failure, dyspnea, orthopnea, respiratory distress.
r. Hypotension includes diastolic hypotension, hypotension, orthostatic hypotension.
s. Thrombosis includes deep vein thrombosis, embolism, embolism venous, pulmonary embolism, splenic infarction, splenic vein
thrombosis, subclavian vein thrombosis, thrombosis, thrombosis in device.

Other clinically important adverse reactions that occurred in less than 10% of patients treated with YESCARTA
include the following:
• Blood and lymphatic system disorders: Coagulopathy (2%)
• Cardiac disorders: Cardiac failure (6%) and cardiac arrest (4%)
• Immune system disorders: Hemophagocytic lymphohistiocytosis/macrophage activation syndrome
(HLH/MAS) (1%), hypersensitivity (1%)
• Infections and infestations disorders: Fungal infections (5%)
• Nervous system disorders: Ataxia (6%), seizure (4%), dyscalculia (2%), and myoclonus (2%)
• Respiratory, thoracic and mediastinal disorders: Pulmonary edema (9%)
• Skin and subcutaneous tissue disorders: Rash (9%)
• Vascular disorders: Capillary leak syndrome (3%)
Laboratory Abnormalities:
Table 4. Grade 3 or 4 Laboratory Abnormalities Occurring in ≥ 10% of Patients in Study 1 Following
Treatment with YESCARTA based on CTCAE (N=108)
Grades 3 or 4 (%)
Lymphopenia 100
Leukopenia 96
Neutropenia 93
Anemia 66
Thrombocytopenia 58
Hypophosphatemia 50
Hyponatremia 19
Uric acid increased 13
Direct Bilirubin increased 13
Hypokalemia 10
Alanine Aminotransferase increased 10
6.2 Immunogenicity
YESCARTA has the potential to induce anti-product antibodies. The immunogenicity of YESCARTA has been
evaluated using an enzyme-linked immunosorbent assay (ELISA) for the detection of binding antibodies against
FMC63, the originating antibody of the anti-CD19 CAR. Three patients tested positive for pre-dose anti-FMC63
antibodies at baseline and Months 1, 3, or 6 in Study 1. There is no evidence that the kinetics of initial expansion and
persistence of YESCARTA, or the safety or effectiveness of YESCARTA, was altered in these patients.
6.3 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of YESCARTA. Because these reactions
are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their
frequency or establish a causal relationship to drug exposure.

Nervous System Disorders

Spinal cord edema, myelitis, quadriplegia and dysphagia
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no available data with YESCARTA use in pregnant women. No animal reproductive and developmental
toxicity studies have been conducted with YESCARTA to assess whether it can cause fetal harm when administered to
a pregnant woman. It is not known if YESCARTA has the potential to be transferred to the fetus. Based on the
mechanism of action, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell
lymphocytopenia. Therefore, YESCARTA is not recommended for women who are pregnant, and pregnancy after
YESCARTA infusion should be discussed with the treating physician.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically
recognized pregnancies is 2% - 4% and 15% - 20%, respectively.
8.2 Lactation
Risk Summary
There is no information regarding the presence of YESCARTA in human milk, the effect on the breastfed infant, and
the effects on milk production. The developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for YESCARTA and any potential adverse effects on the breastfed infant from
YESCARTA or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
Pregnancy status of females with reproductive potential should be verified. Sexually-active females of reproductive
potential should have a pregnancy test prior to starting treatment with YESCARTA.
Contraception
See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective
contraception in patients who receive the lymphodepleting chemotherapy.
There are insufficient exposure data to provide a recommendation concerning duration of contraception following
treatment with YESCARTA.
Infertility
There are no data on the effect of YESCARTA on fertility.
8.4 Pediatric Use
The safety and efficacy of YESCARTA have not been established in pediatric patients.
8.5 Geriatric Use
Clinical trials of YESCARTA did not include sufficient numbers of patients aged 65 years and older to determine
whether they respond differently or have different safety outcomes as compared to younger patients.
11 DESCRIPTION
YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy. To prepare YESCARTA, a
patient’s own T cells are harvested and genetically modified ex vivo by retroviral transduction to express a chimeric
antigen receptor (CAR) comprising a murine anti-CD19 single chain variable fragment (scFv) linked to CD28 and
CD3-zeta co-stimulatory domains. The anti-CD19 CAR T cells are expanded and infused back into the patient, where
they can recognize and eliminate CD19-expressing target cells.
YESCARTA is prepared from the patient’s peripheral blood mononuclear cells, which are obtained via a standard
leukapheresis procedure. The mononuclear cells are enriched for T cells and activated with anti-CD3 antibody in the
presence of IL-2, then transduced with the replication incompetent retroviral vector containing the anti-CD19 CAR
transgene. The transduced T cells are expanded in cell culture, washed, formulated into a suspension, and
cryopreserved. The product must pass a sterility test before release for shipping as a frozen suspension in a patient-
specific infusion bag. The product is thawed prior to infusion [see Dosage and Administration (2.2), How
Supplied/Storage and Handling (16)].
In addition to T cells, YESCARTA may contain NK and NK-T cells. The formulation contains 5% dimethylsulfoxide
(DMSO) and 2.5% albumin (human).
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
YESCARTA, a CD19-directed genetically modified autologous T cell immunotherapy, binds to CD19-expressing
cancer cells and normal B cells. Studies demonstrated that following anti-CD19 CAR T cell engagement with
CD19-expressing target cells, the CD28 and CD3-zeta co-stimulatory domains activate downstream signaling cascades
that lead to T cell activation, proliferation, acquisition of effector functions and secretion of inflammatory cytokines
and chemokines. This sequence of events leads to killing of CD19-expressing cells.
12.2 Pharmacodynamics
After YESCARTA infusion, pharmacodynamic responses were evaluated over a 4-week interval by measuring
transient elevation of cytokines, chemokines and other molecules in blood. Levels of cytokines and chemokines such
as IL-6, IL-8, IL-10, IL-15, TNF-α, IFN-γ, and sIL2Rα were analyzed. Peak elevation was observed within the first 14
days after infusion, and levels generally returned to baseline within 28 days.
Due to the on-target effect of YESCARTA, a period of B-cell aplasia is expected.
Among evaluable subjects with an ongoing response at 24 months, 45% had no detectable B cells at baseline, and a
majority of subjects at Month 3 (80%) and Month 6 (78%) had no detectable B cells. At Month 24, 75% of subjects
had detectable B cells.
12.3 Pharmacokinetics
Following infusion of YESCARTA, anti-CD19 CAR T cells exhibited an initial rapid expansion followed by a decline
to near baseline levels by 3 months. Peak levels of anti-CD19 CAR T cells occurred within the first 7 - 14 days after
YESCARTA infusion.
Age (range: 23 – 76 years) and gender had no significant impact on AUC Day 0 - 28 and Cmax of YESCARTA.
The number of anti-CD19 CAR T cells in blood was positively associated with objective response [complete remission
(CR) or partial remission (PR)]. The median anti-CD19 CAR T cell Cmax levels in responders (n=73) were 205%
higher compared to the corresponding level in nonresponders (n=23) (43.6 cells/μL vs 21.2 cells/μL). Median AUC
Day 0 - 28 in responding patients (n=73) was 251% of the corresponding level in nonresponders (n=23) (557.1 days ×
cells/μL vs. 222.0 days × cells/μL).
Some patients required tocilizumab and corticosteroids for management of CRS and neurologic toxicities. Patients
treated with tocilizumab (n=44) had 262% and 232% higher anti-CD19 CAR T cells as measured by AUC Day 0 - 28
and Cmax respectively, as compared to patients who did not receive tocilizumab (n=57). Similarly, patients that
received corticosteroids (n=26) had 217% and 155% higher AUC Day 0 - 28 and Cmax compared to patients who did
not receive corticosteroids (n=75).
Hepatic and renal impairment studies of YESCARTA were not conducted.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No carcinogenicity or genotoxicity studies have been conducted with YESCARTA. No studies have been conducted to
evaluate the effects of YESCARTA on fertility.
14 CLINICAL STUDIES
Relapsed or Refractory Large B-Cell Lymphoma
A single-arm, open-label, multicenter trial evaluated the efficacy of a single infusion of YESCARTA in adult patients
with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Eligible patients had refractory disease to the
most recent therapy or relapse within 1 year after autologous hematopoietic stem cell transplantation (HSCT). The
study excluded patients with prior allogeneic HSCT, any history of central nervous system lymphoma, ECOG
performance status of 2 or greater, absolute lymphocyte count less than 100/µL, creatinine clearance less than 60
mL/min, hepatic transaminases more than 2.5 times the upper limit of normal, cardiac ejection fraction less than 50%,
or active serious infection.
Following lymphodepleting chemotherapy, YESCARTA was administered as a single intravenous infusion at a target
dose of 2 × 106 CAR-positive viable T cells/kg (maximum permitted dose: 2 × 108 cells). The lymphodepleting
regimen consisted of cyclophosphamide 500 mg/m2 intravenously and fludarabine 30 mg/m2 intravenously, both given
on the fifth, fourth, and third day before YESCARTA. Bridging chemotherapy between leukapheresis and
lymphodepleting chemotherapy was not permitted. All patients were hospitalized for YESCARTA infusion and for a
minimum of 7 days afterward.
Of 111 patients who underwent leukapheresis, 101 received YESCARTA. Of the patients treated, the median age was
58 years (range: 23 to 76 years), 67% were male, and 89% were white. Most (76%) had DLBCL, 16% had transformed
follicular lymphoma, and 8% had primary mediastinal large B-cell lymphoma. The median number of prior therapies
was 3 (range: 1 to 10), 77% of the patients had refractory disease to a second or greater line of therapy, and 21% had
relapsed within 1 year of autologous HSCT.
One out of 111 patients did not receive the product due to manufacturing failure. Nine other patients were not treated,
primarily due to progressive disease or serious adverse reactions following leukapheresis. The median time from
leukapheresis to product delivery was 17 days (range: 14 to 51 days), and the median time from leukapheresis to
infusion was 24 days (range: 16 to 73 days). The median dose was 2.0 × 106 CAR-positive viable T cells/kg (range: 1.1
to 2.2 × 106 cells/kg).
Efficacy was established on the basis of complete remission (CR) rate and duration of response (DOR), as determined
by an independent review committee (Table 5 and Table 6). The median time to response was 0.9 months (range: 0.8
to 6.2 months). Response durations were longer in patients who achieved CR, as compared to patients with a best
response of partial remission (PR) (Table 6). Of the 52 patients who achieved CR, 14 initially had stable disease (7
patients) or PR (7 patients), with a median time to improvement of 2.1 months (range: 1.6 to 5.3 months).

Table 5. Response Rate

Recipients of YESCARTA
(N=101)
Objective Response Ratea 73 (72%)
(95% CI) (62, 81)
Complete Remission Rate 52 (51%)
(95% CI) (41, 62)
Partial Remission Rate 21 (21%)
(95% CI) (13, 30)
CI, confidence interval.
a. Per 2007 revised International Working Group criteria, as assessed by the independent review committee.
Table 6. Duration of Response
From N of 101
Number of Responders 73
DOR (Months)a
Medianb 9.2
(95% CI) (5.4, NE)
Rangec 0.03+, 14.4+
DOR if Best Response is CR (Months)
Medianb NE
(95% CI) (8.1, NE)
Rangec 0.4, 14.4+
DOR if Best Response is PR (Months)
Medianb 2.1
(95% CI) (1.3, 5.3)
Rangec 0.03+, 8.4+
Median Follow-up for DOR (Months)a, b 7.9
CR, complete remission; DOR, duration of response; NE, not estimable; PR, partial remission.
a. Among all responders. DOR is measured from the date of first objective response to the date of progression or death from relapse or
toxicity.
b. Kaplan-Meier estimate.
c. A “+” sign indicates a censored value.

15 REFERENCES
1. Lee DW et al (2014). Current concepts in the diagnosis and management of cytokine release syndrome. Blood.
2014 Jul 10; 124(2): 188-195.
16 HOW SUPPLIED/STORAGE AND HANDLING
YESCARTA is supplied in an infusion bag (NDC 71287-119-01) containing approximately 68 mL of frozen
suspension of genetically modified autologous T cells in 5% DMSO and 2.5% albumin (human).
Each YESCARTA infusion bag is individually packed in a metal cassette (NDC 71287-119-02). YESCARTA is stored
in the vapor phase of liquid nitrogen and supplied in a liquid nitrogen dry shipper.
• Match the identity of the patient with the patient identifiers on the cassette and infusion bag upon receipt.
• Store YESCARTA frozen in the vapor phase of liquid nitrogen (less than or equal to minus 150ºC).
• Thaw before using [see Dosage and Administration (2)].
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Ensure that patients understand the risk of manufacturing failure (1% in clinical trial). In case of a manufacturing
failure, a second manufacturing of YESCARTA may be attempted. In addition, while the patient awaits the product,
additional chemotherapy (not the lymphodepletion) may be necessary and may increase the risk of adverse events
during the pre-infusion period.
Advise patients to seek immediate attention for any of the following:
• Cytokine Release Syndrome (CRS) - Signs or symptoms associated with CRS, including fever, chills,
fatigue, tachycardia, nausea, hypoxia, and hypotension [see Warnings and Precautions (5.1) and Adverse
Reactions (6)].
• Neurologic Toxicities - Signs or symptoms associated with neurologic events, including encephalopathy,
seizures, changes in level of consciousness, speech disorders, tremors, and confusion [see Warnings and
Precautions (5.2) and Adverse Reactions (6)].
• Serious Infections - Signs or symptoms associated with infection [see Warnings and Precautions (5.5) and
Adverse Reactions (6)].
 • Prolonged Cytopenia - Signs or symptoms associated with bone marrow suppression, including
neutropenia, anemia, thrombocytopenia, or febrile neutropenia [see Warnings and Precautions (5.6) and
Adverse Reactions (6)].
Advise patients of the need to:
• Refrain from driving or operating heavy or potentially dangerous machinery after YESCARTA infusion for at
least 8 weeks after infusion [see Warnings and Precautions (5.9)].
• Have periodic monitoring of blood counts.
• Contact Kite at 1-844-454-KITE (5483) if they are diagnosed with a secondary malignancy [see Warnings and
Precautions (5.8)].

Manufactured by, Packed by, Distributed by:

Kite Pharma, Inc.
Santa Monica, CA 90404
US License No 2064
YESCARTA is a trademark of Kite Pharma, Inc. All other trademarks referenced herein are the property of their respective
owners.
© 2020 Kite Pharma, Inc. All Rights Reserved.
125643-GS-002
 MEDICATION GUIDE
YESCARTA (pronounced yes-kar-ta)
(axicabtagene ciloleucel)
Read this Medication Guide before you start your YESCARTA treatment. The more you know about your
treatment, the more active you can be in your care. Talk with your healthcare provider if you have questions about
your health condition or treatment. Reading this Medication Guide does not take the place of talking with your
healthcare provider about your treatment.
What is the most important information I should know about YESCARTA?
YESCARTA may cause side effects that are life-threatening and can lead to death. Call or see your healthcare
provider or get emergency help right away if you get any of the following:
• Fever (100.4°F/38°C or higher)
• Difficulty breathing
• Chills or shaking chills
• Confusion
• Dizziness or lightheadedness
• Severe nausea, vomiting, or diarrhea
• Fast or irregular heartbeat
• Severe fatigue or weakness
It is important to tell your healthcare provider that you received YESCARTA and to show them your YESCARTA
Patient Wallet Card. Your healthcare provider may give you other medicines to treat your side effects.
What is YESCARTA?
YESCARTA is a treatment for your non-Hodgkin lymphoma. It is used when you have failed at least two other
kinds of treatment. YESCARTA is different than other cancer medicines because it is made from your own white
blood cells, which have been modified to recognize and attack your lymphoma cells.
Before getting YESCARTA, tell your healthcare provider about all your medical problems, including if you
have or have had:
• Neurologic problems (such as seizures, stroke, or memory loss)
• Lung or breathing problems
• Heart problems
• Liver problems
• Kidney problems
• A recent or active infection
Tell your healthcare provider about all the medications you take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements.

How will I receive YESCARTA?

• Since YESCARTA is made from your own white blood cells, your blood will be collected by a process
called “leukapheresis” (loo-kah-fur-ee-sis), which will concentrate your white blood cells.
• Your blood cells will be sent to a manufacturing center to make your YESCARTA.
• Before you get YESCARTA, you will get 3 days of chemotherapy to prepare your body.
• When your YESCARTA is ready, your healthcare provider will give it to you through a catheter placed
into your vein (intravenous infusion). The infusion usually takes less than 30 minutes.
 • You will be monitored where you received your treatment daily for at least 7 days after the infusion.
• You should plan to stay close to the location where you received your treatment for at least 4 weeks after
getting YESCARTA. Your healthcare provider will help you with any side effects that may occur.
• You may be hospitalized for side effects and your healthcare provider will discharge you if your side
effects are under control, and it is safe for you to leave the hospital.
• Your healthcare provider will want to do blood tests to follow your progress. It is important that you do
have your blood tested. If you miss an appointment, call your healthcare provider as soon as possible to
reschedule.
What should I avoid after receiving YESCARTA?
• Do not drive, operate heavy machinery, or do other dangerous things for 8 weeks after you get
YESCARTA because the treatment can cause sleepiness, confusion, weakness, temporary memory and
coordination problems.
• Do not donate blood, organs, tissues, and cells for transplantation.

What are the possible or reasonably likely side effects of YESCARTA?

The most common side effects of YESCARTA include:
• Fever (100.4°F/38°C or higher)
• Low white blood cells (can occur with a fever)
• Low red blood cells
• Low blood pressure (dizziness or lightheadedness, headache, feeling tired, short of breath)
• Fast heartbeat
• Confusion
• Difficulty speaking or slurred speech
• Nausea
• Diarrhea
These are not all the possible side effects of YESCARTA. Call your healthcare provider about any side effects that
concern you. You may report side effects to the FDA at 1-800-FDA-1088.

General information about the safe and effective use of YESCARTA

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like
more information about YESCARTA, talk with your healthcare provider. You can ask your healthcare provider for
information about YESCARTA that is written for health professionals. You can get additional information by
contacting Kite at 1-844-454-KITE (5483) or at www.Yescarta.com.

What are the ingredients in YESCARTA?

Active ingredients: axicabtagene ciloleucel.
Inactive ingredients: albumin (human); DMSO.

YESCARTA is a trademark of Kite Pharma, Inc. All other trademarks referenced herein are the property of their respective
owners.
© 2020 Kite Pharma, Inc. All Rights Reserved.