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ZUMA-7: The largest phase 3 CAR T 2L LBCL trial with the longest follow-up1-3

ZUMA-7 study design1-4

  • A phase 3, randomized, open-label, multicenter study of YESCARTA single-infusion therapy vs salvage chemotherapy +/- HDT+ASCT, a current standard therapy,a in 359 adult patients with relapsed/refractory (R/R) large B-cell lymphoma (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 International Prognostic Index (IPI). Two recipients of nonconformal product are included in the YESCARTA arm for the efficacy analysis
  • Patients were required to have primary refractory disease or relapse 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

Key inclusion criteria: histologically proven LBCL; R/R disease after 1L chemoimmunotherapy (anti-CD20 monoclonal antibody and anthracycline-containing regimen); intent to proceed to HDT+ASCT; radiographically documented disease; no CNS involvement by lymphoma; ≥2 weeks (or 5 half-lives) since prior systemic cancer therapy; ≥18 years of age; ECOG PS of 0 or 1; adequate bone marrow, renal, hepatic, pulmonary, and cardiac function; and negative pregnancy test, if applicable.5

Key exclusion criteria: PMBCL; any history of CNS lymphoma; need for urgent therapy due to tumor mass effect; active or serious infections; and ECOG PS of ≥2.1

ZUMA-7 head-to-head study design.

Primary Endpoint1:

Event-free survival (EFS)

Select Secondary Endpoints4:

  • ORR
  • OS
  • DOR
  • PFS
  • PROs
  • Safety

aStandard-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

bRefractory disease was defined as no complete response (CR) to 1L therapy; relapsed disease was defined as CR followed by biopsy-proven disease relapse ≤12 months from completion of 1L therapy.2

cYESCARTA patients underwent leukapheresis followed by conditioning chemotherapy with cyclophosphamide (500 mg/m 2/day) and fludarabine (30 mg/m2/day) 5, 4, and 3 days before receiving a single YESCARTA infusion (target intravenous dose, 2x106 CAR T cells/kg). Optional bridging therapy was limited to glucocorticoids only.2

d55% of patients randomized to the standard therapy arm subsequently received CD19-directed CAR T therapy.1

YESCARTA was studied across a broad range of patients with R/R LBCL ≤12 months1

  YESCARTA (N=180) Standard therapy (N=179)
Age, median (range), years 58 (21-80) 60 (26-81)
≥65 51 (28%) 58 (32%)
Sex
Male 110 (61%) 127 (71%)
Female 70 (39%) 52 (29%)
Ecog Ps
0 95 (53%) 100 (56%)
1 85 (47%) 79 (44%)
2L age-adjusted IPIe
≤1 98 (54%) 100 (56%)
2-3 82 (46%) 79 (44%)
Disease typef
LBCL NOS 110 (61%) 116 (65%)
HGBCL 43 (24%) 27 (15%)
TFL 19 (11%) 27 (15%)
Otherg 8 (5%) 9 (5%)
Response to 1L therapy
Primary refractory 133 (74%) 131 (73%)
Relapse at ≤12 months 47 (26%) 48 (27%)
High-risk characteristics
Double- or triple-hit disease 31 (17%) 25 (14%)
Double-expressor lymphoma 57 (32%) 62 (35%)

From N Engl J Med, Locke FL, Miklos DB, Jacobson CA, et al., Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma, 386(7):640-654.
Copyright © 2022. Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

eValues are the second-line age-adjusted IPI at randomization, which were similar to the second-line age-adjusted IPI according to the investigator as entered into the clinical database. The second-line age-adjusted IPI is used to assess prognostic risk on the basis of various factors after adjustment for patient age and extranodal status at the time of diagnosis of refractory disease; risk categories are assessed as low (0 factors), intermediate (1 factor), or high (2 or 3 factors).2

fDisease type according to the investigator.2

gIncludes T-cell– or histiocyte–rich large B-cell lymphoma, Epstein–Barr virus–positive diffuse large B-cell lymphoma, primary cutaneous diffuse large B-cell lymphoma (leg type), and other disease types according to the investigator.2

More patients successfully completed treatment with YESCARTA vs standard therapy2

94% COMPLETED TREATMENT WITH YESCARTA

6% of patients (n=10/180) did not receive YESCARTA

Reasons patients did not undergo leukapheresis:

  • Disease progression (n=1)
  • Other (n=1)

Reasons lymphodepleting chemotherapy was not received following leukapheresis:

  • AE (n=2)
  • Deathh (n=2)
  • Disease progression (n=1)
  • Other (n=1)

Reasons YESCARTA was not received following lymphodepleting chemotherapy:

  • AE (n=2)
  • 33% of patients treated with YESCARTA received bridging corticosteroid therapy1,i
  • Patients who did not receive treatment due to disease progression: 1% with YESCARTA (n=2/180) vs 40% with standard therapy (n=71/179)2

h1 subject died from sepsis deemed unrelated to leukapheresis and 1 subject died due to nonradiologic disease progression.8

iBridging therapy was restricted to glucocorticoids to avoid the progression of lymphoma during the manufacturing process and to isolate the effects of CAR T-cell therapy as second-line therapy.2

35% COMPLETED TREATMENT WITH STANDARD THERAPY

65% of patients (n=117/179) did not receive HDT+ASCT

Reasons standard therapy was not received following randomization:

  • Subject request (n=8)
  • Other (n=2)
  • Lost to follow-up (n=1)

Reasons for not proceeding following ≥1 dose of salvage chemotherapy:

  • Disease progression (n=56)
  • Stable disease (n=27)
  • AE (n=1)
  • Lack of response to salvage chemoimmunotherapy with R-ICE (n=1)
  • Did not tolerate R-GDP and switched to R-ICE (n=1)
  • Changed treatment after R-DHAP due to renal impairment (n=1)
  • Insufficient overall response (n=1)

Reasons for not undergoing leukapheresis:

  • Disease progression (n=9)
  • Insufficient response (n=1)
  • AE (n=1)

Reasons HDT not received following leukapheresis:

  • Disease progression (n=5)

Reasons ASCT not received following HDT:

  • Disease progression (n=1)
  • Other (n=1)
  • 33% of patients treated with YESCARTA received bridging corticosteroid therapy1,i
  • Patients who did not receive treatment due to disease progression: 1% with YESCARTA (n=2/180) vs 40% with standard therapy (n=71/179)2

h1 subject died from sepsis deemed unrelated to leukapheresis and 1 subject died due to nonradiologic disease progression.8

iBridging therapy was restricted to glucocorticoids to avoid the progression of lymphoma during the manufacturing process and to isolate the effects of CAR T-cell therapy as second-line therapy.2

YESCARTA demonstrated significant improvement in EFS vs salvage chemotherapy +/- HDT+ASCT, a current standard therapy (N=359)1,2

Line chart of event-free survival in ZUMA-7.

The tick marks represent censored patients. Patients who did not meet the event criteria had their data censored; disease-progression events and censoring times were determined on the basis of blinded central review.2 At 24 months, 48 patients in the YESCARTA arm and 26 patients in the standard therapy arm were censored.10

  • The estimated 18-month EFS was 41.5% (95% CI, 34.2-48.6) in the YESCARTA arm and 17.0% (95% CI, 11.8-23.0) in the standard therapy arm1

Quadrupled mEFS with YESCARTA vs standard therapy
(8.3 months [95% CI, 4.5-15.8] vs 2 months [95% CI, 1.6-2.8])1,k

jEFS rate at 2 years is a KM estimate and should be carefully interpreted due to the number of censored patients. Data are not included in the YESCARTA Prescribing Information.2

kKM estimate.1

EFS improvement was consistent across a broad range of 2L LBCL patients9

Forest plot of event-free survival in selected subgroups in ZUMA-7.

These results represent prespecified subgroup analyses of the ZUMA-7 study; however, these analyses were not study objectives and the study was therefore not powered or adjusted for multiplicity to assess efficacy in these subgroups.2

Additional endpoints

YESCARTA demonstrated deep and durable remissions1

Bar chart showing objective response rate (ORR) and complete response (CR) rate.
  • The median DOR was 26.9 months (95% CI, 13.6-NE) in patients treated with YESCARTA (number of responders=150)5,m

lAssessed per Cochran-Mantel-Haenszel method for best objective response rate. For all stratified analyses, stratification was based on response to 1L therapy (primary refractory vs relapse within 6 months of 1L therapy vs relapse within >6 but ≤12 months) and 2L age-adjusted IPI.1

mThe estimated median DOR was 28.4 months (95% CI, 26.9-NE) in patients who achieved CR and 1.6 months (95% CI, 1.4-1.9) in patients who achieved a best response of PR.1

YESCARTA demonstrated longer progression-free survival (PFS) vs standard therapy1

Line chart showing mPFS.

PFS was a prespecified secondary endpoint in the ZUMA-7 study; however, the study was not powered to assess PFS efficacy. 2

  • The interim analysis of overall survival has not met the criteria for statistical significance1
  • 55% of patients randomized to the standard therapy arm subsequently received CD19-directed CAR T therapy1

nKM estimate.1

Results from the health-related quality of life (HRQoL) analysis set favored YESCARTA at day 100 from baseline vs standard therapy12,13

  • YESCARTA was evaluated across validated patient-reported outcome measures, including EORTC QLQ-C30 Global Health Status/QoLo (N=296)
    • 165 subjects in the YESCARTA arm and 131 subjects in the standard therapy arm had baseline PROs and ≥1 follow-up measure and were included for analysis in the QoL analysis set
    • Using Global Health Status/QoL as a representative measure of the EORTC QLQ-C30, 208 patients (70%) completed the day 100 assessment (88% YESCARTA; 47% standard therapy)
  • A clinically meaningful difference in mean EORTC QLQ-C30 Global Health Status/QoL scores from baseline to day 100 was reported with YESCARTA vs standard therapy (estimated difference: 18.1 [95% CI, 12.3-23.9])
    • The MID was defined as a change of ≥10-point improvement from screening for each EORTC QLQ-C30 score
  • Per an exploratory analysis, by day 100 to day 150 (months 3 to 5), mean estimated scores with YESCARTA returned to or exceeded scores at baseline vs 9 months later for standard therapy
    • Score comparisons at later timepoints warrant cautious interpretation because attrition due to disease progression, new lymphoma therapy, or death was disproportionately higher in the standard therapy arm and may select for patients with the best outcomes
Line chart showing change from screening by visit in EORTC QLQ-C30 Global Health Status/QoL score.

HRQoL data are descriptive and were not powered or adjusted for multiplicity. These data are not included in the YESCARTA Prescribing Information.

oModel included variables for treatment, time, and treatment by time interaction (primary analysis) and controlled for response to first-line therapy (primary refractory, relapse ≤6 months of first-line therapy vs relapse >6 and ≤12 months of first-line therapy) and age-adjusted IPI (0 to 1 vs 2 to 3) at time of screening.13

See Patient-reported outcomes (PROs) in ZUMA-7

Patient-reported outcomes (PROs) in ZUMA-714,15

EORTC QLQ-C30 is a 30-item questionnaire that provides a multidimensional assessment of HRQoL through several scales:

  • 5 multi-item functional scales (physical, role, emotional, cognitive, and social functioning)
  • 3 symptom scales (fatigue, nausea/vomiting, and pain)
  • 6 single-item symptom scales (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties)
  • 2 global scales (Global Health Status and HRQoL)
  • No item occurs in more than one scale
  • All of the scales and single-item measures range in score from 0 to 100. Higher scores for the functioning scales and Global Health Status denote a better level of functioning (ie, a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (ie, a worse state of the patient)
  • Each PRO score was to be examined via a series of MMRM that examined both the individual change in HRQoL scores over time and systematic differences between groups. The base MMRM was to fit to each PRO score with terms for treatment arm, time point (treated as discrete), and treatment by time interaction
  • Via the MMRM, planned comparisons were to be conducted between treatment arms at predetermined specific time points of interest (study days 100 and 150 and months 9, 12, 15, 18, 21, and 24)
    • MMRM is often used in randomized long-term trials that include repeated outcome measurements for each patient16
    • MMRM analysis takes into account the correlation seen within single patients so as to prevent biased results17

1L=first line; 2L=second line; AE-adverse event; ASCT=autologous stem cell transplant; CAR=chimeric antigen receptor; CAR T=chimeric antigen receptor T cell; CD19-cluster of differentiation 19; CD20=cluster of differentiation 20; CI=confidence interval; CNS=central nervous system; CR=complete response; DLBCL=diffuse large B-cell lymphoma; DOR=duration of response; ECOG PS=Eastern Cooperative Oncology Group performance status; EORTC QLQ-C30=European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire; HDT=high-dose therapy; HGBCL=high-grade B-cell lymphoma; HR=hazard ratio; KM=Kaplan-Meier; mEFS=median event-free survival; MID=minimally important difference; MMRM=mixed-effect models for repeated measures; mPFS=median progression-free survival; NE=not estimable; NOS=not otherwise specified; ORR=objective response rate; OS=overall survival; PMBCL=primary mediastinal large B-cell lymphoma; PR=partial response; PFS=progression-free survival; QoL=quality of life; 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; TFL=transformed follicular lymphoma.

YESCARTA demonstrated a well-characterized safety profile1

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IMPORTANT SAFETY INFORMATION

BOXED 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.
  • 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.
  • YESCARTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the YESCARTA and TECARTUS REMS Program.

CYTOKINE RELEASE SYNDROME (CRS)
CRS, including fatal or life-threatening reactions, occurred. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL), including ≥ Grade 3 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 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.

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 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) that were fatal or life-threatening occurred. 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 for 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 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 called the YESCARTA and TECARTUS REMS Program which requires that: Healthcare facilities that dispense and administer YESCARTA must be enrolled and comply with the REMS requirements and must have on-site, immediate access to a minimum of 2 doses of tocilizumab 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.YescartaTecartusREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS
Allergic reactions, including serious hypersensitivity reactions or anaphylaxis, may occur with the infusion of YESCARTA.

SERIOUS INFECTIONS
Severe or life-threatening infections occurred. Infections (all grades) occurred in 45% of patients with NHL. ≥ Grade 3 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 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. 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
Secondary malignancies may develop. Monitor life-long for secondary malignancies. In the event that one 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; 2022. 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. Data on file [1]. Kite Pharma, Inc; 2021. 4. Data on file [2]. Kite Pharma, Inc; 2021. 5. 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 (suppl). doi:10.1056/NEJMoa2116133. 6. Locke FL, Miklos DB, Jacobson CA, et al. Primary analysis of ZUMA-7: a phase 3 randomized trial of axicabtagene ciloleucel versus standard-of-care therapy in patients with relapsed/refractory large B-cell lymphoma. Presented at: 63rd ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Plenary Abstract 2. 7. Data on file [3]. Kite Pharma, Inc; 2021. 8. Data on file [4]. Kite Pharma, Inc; 2021. 9. Data on file [5]. Kite Pharma, Inc; 2021. 10. Data on file. Kite Pharma, Inc; 2022. 11. Data on file [6]. Kite Pharma, Inc; 2021. 12. Elsawy M, Chavez JC, Aviv I, et al. Patient-reported outcomes in a phase 3, randomized, open-label study evaluating the efficacy of axicabtagene ciloleucel (axi-cel) versus standard of care therapy in patients with relapsed/refractory large B-cell lymphoma (ZUMA-7). Presented at: 63rd ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 430. 13. Data on file [7]. Kite Pharma, Inc; 2021. 14. Data on file [8]. Kite Pharma, Inc; 2021. 15. Data on file [9]. Kite Pharma, Inc; 2021. 16. Bell ML, Rabe BA. The mixed model for repeated measures for cluster randomized trials: a simulation study investigating bias and type I error with missing continuous data. Trials. 2020;21(1):148. 17. Detry MA, Ma Y. Analyzing repeated measurements using mixed models. JAMA. 2016;315(4):407-408 .