YESCARTA® (axicabtagene ciloleucel) Safety Information

In ZUMA-7, YESCARTA demonstrated a well-characterized safety profile; AES were managed per established guidance¹

In the ZUMA-7 trial, safety was evaluated in 168 patients with primary refractory or first relapse of LBCL treated with YESCARTA¹
ZUMA-7 safety data were consistent with previous YESCARTA ≥3L LBCL clinical trial data and real-world experience^2-5
- No new safety signals were identified

View Study Design

ZUMA-7 STUDY DESIGN^1,2,6,7

A phase 3, randomized, open-label, multicenter study of YESCARTA single-infusion therapy vs salvage chemotherapy +/- HDT+ASCT, a current standard therapy,* in 359 adult patients with R/R LBCL. Patients were randomized 1:1 to YESCARTA (N=180) and standard therapy (N=179) and stratified by response to 1L therapy and 2L age-adjusted IPI. Two recipients of nonconformal product are included in the YESCARTA arm for the efficacy analysis
Patients had primary refractory disease or relapsed within 12 months following completion of 1L therapy
The primary endpoint was event-free survival (EFS)

The median follow-up time for the primary analysis was 19.2 months
EFS is defined as the time from randomization to the earliest date of disease progression or relapse, best response of stable disease up to and including the day 150 assessment, commencement of new lymphoma therapy, or death from any cause. Response was assessed by an independent review committee, per the International Working Group Lugano classification (Cheson 2014)

Select secondary endpoints included ORR, DOR, OS, PFS, PROs, and safety

*Standard-care chemotherapy could include 2 to 3 cycles of R-ICE, R-GDP, R-ESHAP, R-DHAP, or R-DHAX followed by high-dose chemotherapy and autologous stem cell transplant in patients with disease response.²

Cytokine release syndrome (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with YESCARTA.¹

Management of CRS

At the Authorized Treatment Center, ensure that 2 doses of tocilizumab are available prior to infusion of YESCARTA. 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. Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension.¹

If CRS is suspected, manage according to the recommendations in Section 2.3 of the full Prescribing Information.

CRS GRADING AND MANAGEMENT GUIDANCE¹

CRS Grade	Tocilizumab	Corticosteroids
Grade 1 Symptoms require symptomatic treatment only (eg, fever, nausea, fatigue, headache, myalgia, malaise).	If symptoms (eg, fever) not improving after 24 hours, consider managing as Grade 2.	If not improving after 3 days, administer 1 dose of dexamethasone 10 mg intravenously.
Grade 2 Symptoms require and respond to moderate intervention. Oxygen requirement less than 40% FiO₂ or hypotension responsive to fluids or low-dose of 1 vasopressor or Grade 2 organ toxicity.	Administer tocilizumab 8 mg/kg intravenously over 1 hour (not to exceed 800 mg). If no clinical improvement in the signs and symptoms of CRS after the first dose, repeat tocilizumab every 8 hours as needed. Limit to a maximum of 3 doses in a 24-hour period; maximum total of 4 doses. If improving, discontinue tocilizumab.	Administer dexamethasone 10 mg intravenously once daily. If improving, manage as Grade 1 above and continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as appropriate grade below.
Grade 3 Symptoms require and respond to aggressive intervention. Oxygen requirement greater than or equal to 40% FiO₂ or hypotension requiring high-dose or multiple vasopressors or Grade 3 organ toxicity or Grade 4 transaminitis.	Per Grade 2. If improving, manage as appropriate grade above.	Dexamethasone 10 mg intravenously 3 times a day. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as Grade 4.
Grade 4 Life-threatening symptoms. Requirements for ventilator support, continuous veno-venous hemodialysis (CVVHD) or Grade 4 organ toxicity (excluding transaminitis).	Per Grade 2. If improving, manage as appropriate grade above.	Administer methylprednisolone 1000 mg intravenously once per day for 3 days. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, consider methylprednisolone 1000 mg 2-3 times a day or alternate therapy.^†

^†Alternate therapy includes (but is not limited to): anakinra, siltuximab, ruxolitinib, cyclophosphamide, IVIG, and ATG.¹

Patients who experience Grade ≥2 CRS (eg, 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.¹

Neurologic toxicities

Neurologic toxicities (including immune effector cell-associated neurotoxicity syndrome [ICANS]) that were fatal or life-threatening occurred following treatment with YESCARTA.¹

Management of neurologic toxicities

When managing neurologic toxicity/ICANS at the Authorized Treatment Center, rule out other causes of neurologic symptoms. Patients who experience Grade ≥2 neurologic toxicities/ICANS should be monitored with continuous cardiac telemetry and pulse oximetry. Provide intensive-care supportive therapy for severe or life-threatening neurologic toxicities. Consider levetiracetam for seizure prophylaxis for any grade of neurologic toxicities.¹

See Section 2.3 of the full Prescribing Information for additional monitoring and management guidance relating to neurologic toxicities.

NEUROLOGIC TOXICITY/ICANS GRADING AND MANAGEMENT GUIDANCE^1‡

Grading Assessment^‡	Concurrent CRS	No Concurrent CRS
Grade 1	Administer tocilizumab per CRS Grading and Management table above for management of Grade 1 CRS. In addition, administer 1 dose of dexamethasone 10 mg intravenously. If not improving after 2 days, repeat dexamethasone 10 mg intravenously.	Administer 1 dose of dexamethasone 10 mg intravenously. If not improving after 2 days, repeat dexamethasone 10 mg intravenously.
Grade 1	Consider levetiracetam for seizure prophylaxis.
Grade 2	Administer tocilizumab per CRS Grading and Management table above for management of Grade 2 CRS. In addition, administer dexamethasone 10 mg intravenously 4 times a day. If improving, continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as appropriate grade below.	Administer dexamethasone 10 mg intravenously 4 times a day. If improving, continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as appropriate grade below.
Grade 2	Consider levetiracetam for seizure prophylaxis.
Grade 3	Administer tocilizumab per CRS Grading and Management table above for management of Grade 2 CRS. In addition, administer methylprednisolone 1000 mg intravenously once daily. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, manage as Grade 4.	Administer methylprednisolone 1000 mg intravenously once daily. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, manage as Grade 4.
Grade 3	Consider levetiracetam for seizure prophylaxis.
Grade 4	Administer tocilizumab per CRS Grading and Management table above for management of Grade 2 CRS. In addition, administer methylprednisolone 1000 mg intravenously twice per day. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, consider 1000 mg of methylprednisolone intravenously 3 times a day or alternate therapy.^§	Administer methylprednisolone 1000 mg intravenously twice per day. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, consider 1000 mg of methylprednisolone intravenously 3 times a day or alternate therapy.^§
Grade 4	Consider levetiracetam for seizure prophylaxis.

^‡Severity based on Common Terminology Criteria for Adverse Events.¹

^§Alternate therapy includes (but is not limited to): anakinra, siltuximab, ruxolitinib, cyclophosphamide, IVIG, and ATG.¹

Adverse reactions¹

The most common non-laboratory adverse reactions to YESCARTA (incidence ≥20%) included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal pain, nausea, febrile neutropenia, chills, cough, infection with unspecified pathogen, dizziness, tremor, decreased appetite, edema, hypoxia, abdominal pain, aphasia, constipation, and vomiting.

Serious adverse reactions occurred in 50% of patients. The most common serious adverse reactions (>5%) included CRS, fever, encephalopathy, hypotension, infection with unspecified pathogen, and pneumonia. Fatal adverse reactions occurred in 2% of patients.

The most common (≥10%) Grade 3 or higher non-laboratory adverse reactions included febrile neutropenia, encephalopathy, and hypotension.

This is not a complete list of adverse events associated with YESCARTA. For additional information, please see Important Safety Information.

adverse reactions observed in at least 10% of patients treated with YESCARTA in ZUMA-7¹

Adverse Reaction	Yescarta (n=168)
Adverse Reaction	Any grade (%)	Grade ≥3 (%)
Febrile neutropenia	31	31
Cardiac disorders
Tachycardia^a	43	2
Arrhythmia^b	14	3
Gastrointestinal disorders
Diarrhea^c	42	3
Nausea	40	2
Abdominal pain^d	20	4
Constipation	20	0
Vomiting	20	0
Dry mouth	10	0
General disorders and administration site conditions
Fever^e	93	9
Fatigue^f	52	7
Chills	28	1
Edema^g	23	1
Immune system disorders
Cytokine release syndrome	92	7
Hypogammaglobulinemia	11	0
Infections and infestations
Infections with pathogen unspecified	25	8
Viral infections	15	4
Bacterial infections	10	5
Fungal infections	10	1
Metabolism and nutrition disorders
Decreased appetite	24	4
Musculoskeletal and connective tissue disorders
Musculoskeletal pain^h	40	1
Motor dysfunctionⁱ	15	4
Nervous system disorders
Encephalopathy^j	46	18
Headache^k	41	3
Tremor	25	1
Dizziness^l	25	4
Aphasia	20	7
Neuropathy peripheral^m	11	2
Psychiatric disorders
Insomniaⁿ	13	0
Delirium^o	12	4
Renal and urinary disorders
Renal insufficiency^p	11	2
Respiratory, thoracic, and mediastinal disorders
Cough^q	27	1
Hypoxia	21	9
Skin and subcutaneous tissue disorders
Rash^r	17	1
Vascular disorders
Hypotension^s	47	11

The following events were also counted in the incidence of CRS: coagulopathy, tachycardia, arrhythmia, cardiac failure, diarrhea, nausea, vomiting, fever, fatigue, chills, edema, decreased appetite, musculoskeletal pain, headache, tremor, dizziness, renal insufficiency, cough, hypoxia, dyspnea, pleural effusion, respiratory failure, rash, hypotension, and hypertension.

^aTachycardia includes tachycardia, sinus tachycardia.

^bArrhythmia includes arrhythmia, atrial fibrillation, bradycardia, electrocardiogram QT prolonged, extrasystoles, sinus bradycardia, supraventricular extrasystoles, supraventricular tachycardia, ventricular extrasystoles, ventricular tachycardia.

^cDiarrhea includes diarrhea, colitis.

^dAbdominal pain includes abdominal pain, abdominal discomfort, abdominal pain lower, abdominal pain upper, dyspepsia.

^eFever includes pyrexia.

^fFatigue includes fatigue, asthenia, malaise.

^gEdema includes edema, face edema, fluid overload, generalized edema, hypervolemia, localized edema, edema genital, edema peripheral, periorbital edema, peripheral swelling, pulmonary edema.

^hMusculoskeletal pain includes musculoskeletal pain, arthralgia, arthritis, back pain, bone pain, flank pain, groin pain, musculoskeletal chest pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity.

ⁱMotor dysfunction includes muscle contractions involuntary, muscle spasms, muscle twitching, muscular weakness.

^jEncephalopathy includes encephalopathy, altered state of consciousness, amnesia, apraxia, bradyphrenia, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, dysarthria, dysgraphia, dyspraxia, lethargy, loss of consciousness, memory impairment, mental impairment, mental status changes, metabolic encephalopathy, slow speech, somnolence, toxic encephalopathy.

^kHeadache includes headache and tension headache.

^lDizziness includes dizziness, dizziness postural, presyncope, syncope, vertigo.

^mNeuropathy peripheral includes hypoesthesia, lumbar radiculopathy, neuropathy peripheral, paresthesia, peroneal nerve palsy, sciatica.

ⁿInsomnia includes insomnia and sleep deficit.

^oDelirium includes delirium, agitation, delusion, disorientation, hallucination, irritability, restlessness.

^pRenal insufficiency includes acute kidney injury, blood creatinine increased, chronic kidney disease.

^qCough includes cough, productive cough, upper-airway cough syndrome.

^rRash includes rash, dermatitis, dermatitis allergic, dermatitis bullous, drug eruption, erythema, pruritus, rash macular, rash maculo-papular, rash pruritic, urticaria.

^sHypotension includes hypotension, capillary leak syndrome, orthostatic hypotension.

Patient monitoring at Authorized Treatment Centers¹

Monitoring takes place at the YESCARTA Authorized Treatment Centers where there are approved safety protocols and physicians who are specially trained in YESCARTA administration and adverse event management. Long-term monitoring should continue in the community setting.

7days

Patients will be monitored at least daily for 7 days at the Authorized Treatment Center following infusion for signs and symptoms of CRS and neurologic toxicities.

4Weeks

Patients will be instructed to remain within proximity of the Authorized Treatment Center for at least 4 weeks following infusion. Monitor patients for signs or symptoms of CRS or neurologic toxicities for 4 weeks after infusion. Patients will be counseled to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicities occur at any time.

1L=first line; 2L=second line; 3L=third line; ASCT=autologous stem cell transplant; ATG=anti-thymocyte globulin; DOR=duration of response; HDT=high-dose therapy; IPI=International Prognostic Index; IVIG=intravenous immunoglobulin; LBCL=large B-cell lymphoma; ORR=objective response rate; OS=overall survival; PFS=progression-free survival; PRO=patient-reported outcome; R-DHAP=rituximab, dexamethasone, high-dose cytarabine, cisplatin; R-DHAX=rituximab, dexamethasone, high-dose cytarabine, oxaliplatin; R-ESHAP=rituximab, etoposide, methylprednisolone, high-dose cytarabine, cisplatin; R-GDP=rituximab, gemcitabine, dexamethasone, cisplatin; R-ICE=rituximab, ifosfamide, carboplatin, etoposide; R/R=relapsed/refractory.

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IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, and SECONDARY HEMATOLOGICAL MALIGNANCIES

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.
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.
T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA.
YESCARTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the YESCARTA and TECARTUS REMS.

CYTOKINE RELEASE SYNDROME (CRS)
CRS, including fatal or life-threatening reactions, occurred following treatment with YESCARTA. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL), including ≥ Grade 3 CRS in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including ≥ Grade 3 in 9%. Among patients with LBCL who died after receiving YESCARTA, 4 had ongoing CRS events at the time of death. For patients with LBCL in ZUMA-1, the median time to onset of CRS was 2 days following infusion (range: 1-12 days) and the median duration was 7 days (range: 2-58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1-10 days) and the median duration was 7 days (range: 2-43 days).

CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 CRS in 8%. Among patients with iNHL who died after receiving YESCARTA, 1 patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1-20 days) and median duration was 6 days (range: 1-27 days) for patients with iNHL.

Key manifestations of CRS (≥ 10%) in all patients combined included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious events that may be associated with CRS include, cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), renal insufficiency, cardiac failure, respiratory failure, cardiac arrest, capillary leak syndrome, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

The impact of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received tocilizumab and/or corticosteroids for ongoing Grade 1 events, CRS occurred in 93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients experienced a Grade 4 or 5 event. The median time to onset of CRS was 2 days (range: 1-8 days) and the median duration of CRS was 7 days (range: 2-16 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Thirty-one of the 39 patients (79%) developed CRS and were managed with tocilizumab and/or therapeutic doses of corticosteroids with no patients developing ≥ Grade 3 CRS. The median time to onset of CRS was 5 days (range: 1-15 days) and the median duration of CRS was 4 days (range: 1-10 days). Although there is no known mechanistic explanation, consider the risk and benefits of prophylactic corticosteroids in the context of pre-existing comorbidities for the individual patient and the potential for the risk of Grade 4 and prolonged neurologic toxicities.

Ensure that 2 doses of tocilizumab are available prior to YESCARTA infusion. Monitor patients for signs and symptoms of CRS following infusion at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter. 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 including immune effector cell-associated neurotoxicity syndrome (ICANS) that were fatal or life-threatening occurred following treatment with YESCARTA. Neurologic toxicities occurred in 78% (330/422) of patients with NHL receiving YESCARTA, including ≥ Grade 3 in 25%.

Neurologic toxicities occurred in 87% (94/108) of patients with LBCL in ZUMA-1, including ≥ Grade 3 in 31% and in 74% (124/168) of patients in ZUMA-7 including ≥ Grade 3 in 25%. The median time to onset was 4 days (range: 1-43 days) and the median duration was 17 days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5 days (range: 1-133 days) and median duration was 15 days in patients with LBCL in ZUMA-7. Neurologic toxicities occurred in 77% (112/146) of patients with iNHL, including ≥ Grade 3 in 21%. The median time to onset was 6 days (range: 1-79 days) and the median duration was 16 days. Ninety-eight percent of all neurologic toxicities in patients with LBCL and 99% of all neurologic toxicities in patients with iNHL occurred within the first 8 weeks of YESCARTA infusion. Neurologic toxicities occurred within the first 7 days of infusion in 87% of affected patients with LBCL and 74% of affected patients with iNHL.

The most common neurologic toxicities (≥ 10%) in all patients combined included encephalopathy (50%), headache (43%), tremor (29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia (10%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events, including aphasia, leukoencephalopathy, dysarthria, lethargy, and seizures occurred. Fatal and serious cases of cerebral edema and encephalopathy, including late-onset encephalopathy, have occurred.

The impact of tocilizumab and/or corticosteroids on the incidence and severity of neurologic toxicities was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received corticosteroids at the onset of Grade 1 toxicities, neurologic toxicities occurred in 78% (32/41) and 20% (8/41) had Grade 3 neurologic toxicities; no patients experienced a Grade 4 or 5 event. The median time to onset of neurologic toxicities was 6 days (range: 1-93 days) with a median duration of 8 days (range: 1-144 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Of those patients, 85% (33/39) developed neurologic toxicities; 8% (3/39) developed Grade 3, and 5% (2/39) developed Grade 4 neurologic toxicities. The median time to onset of neurologic toxicities was 6 days (range: 1-274 days) with a median duration of 12 days (range: 1-107 days). Prophylactic corticosteroids for management of CRS and neurologic toxicities may result in higher grade of neurologic toxicities or prolongation of neurologic toxicities, delay the onset, and decrease the duration of CRS.

Monitor patients for signs and symptoms of neurologic toxicities following infusion at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter, and treat promptly.

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 and TECARTUS REMS. The required components of the YESCARTA and TECARTUS 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.

Further information is available at www.YescartaTecartusREMS.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 after YESCARTA infusion. Infections (all grades) occurred in 45% of patients with NHL. Grade 3 or higher infections occurred in 17% of patients, including ≥ Grade 3 infections with an unspecified pathogen in 12%, bacterial infections in 5%, viral infections in 3%, and fungal infections in 1%. YESCARTA should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.

Febrile neutropenia was observed in 36% of patients with NHL 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.

In immunosuppressed patients, including those who have received YESCARTA, life-threatening and fatal opportunistic infections including disseminated fungal infections (e.g., candida sepsis and aspergillus infections) and viral reactivation (e.g., human herpes virus-6 [HHV-6] encephalitis and JC virus progressive multifocal leukoencephalopathy [PML]) have been reported. The possibility of HHV-6 encephalitis and PML should be considered in immunosuppressed patients with neurologic events and appropriate diagnostic evaluations should be performed.

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, has occurred in patients treated with drugs directed against B cells, including YESCARTA. Perform screening for HBV, HCV, and HIV and management 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. Grade 3 or higher cytopenias not resolved by Day 30 following YESCARTA infusion occurred in 39% of all patients with NHL and included neutropenia (33%), thrombocytopenia (13%), and anemia (8%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA
B-cell aplasia and hypogammaglobulinemia can occur in patients receiving YESCARTA. Hypogammaglobulinemia was reported as an adverse reaction in 14% of all patients with NHL. 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 treated with YESCARTA may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes.

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 non-laboratory adverse reactions (incidence ≥ 20%) in patients with LBCL in ZUMA-7 included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal pain, nausea, febrile neutropenia, chills, cough, infection with unspecified pathogen, dizziness, tremor, decreased appetite, edema, hypoxia, abdominal pain, aphasia, constipation, and vomiting.

The most common adverse reactions (incidence ≥ 20%) in patients with LBCL in ZUMA-1 included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections with pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

INDICATIONSMORE

YESCARTA^® is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.
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.

Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.

Please see full Prescribing Information, including BOXED WARNING and Medication Guide.

Authorized Treatment Centers are independent facilities certified to dispense Kite CAR T therapies. Choice of an Authorized Treatment Center is within the sole discretion of the physician and patient. Kite does not endorse any individual treatment sites.

References: 1. YESCARTA (axicabtagene ciloleucel). Prescribing information. Kite Pharma, Inc; 2024. 2. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640-654. 3. Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial. Lancet Oncol. 2019;20(1):31-42. 4. Nastoupil LJ, Jain MD, Feng L, et al. Standard-of-care axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma: results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2020;38(27):3119-3128. 5. Sanderson R, Benjamin R, Patten P, et al. Axi-cel for large B-cell lymphoma: real-world outcomes from a prospective UK cohort. Poster presented at: European Society for Blood and Marrow Transplantation (EBMT) 46th Annual Meeting; August 29-September 1, 2020; Virtual. 6. Data on file [1]. Kite Pharma, Inc; 2021. 7. Data on file [2]. Kite Pharma, Inc; 2021.

In ZUMA-7, YESCARTA demonstrated a well-characterized safety profile; AES were managed per established guidance1

ZUMA-7 STUDY DESIGN1,2,6,7