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YESCARTA demonstrated a well-characterized safety profile; AEs were managed per established guidance1

Consistent safety profile in both clinical trials and the real world1-5

2L and 3L trials

  • ZUMA-7: safety was evaluated in 168 patients with primary refractory or first relapse of LBCL treated with YESCARTA1
  • ZUMA-1: Phase 2, open-label, single-arm, multicenter trial of YESCARTA in 101 adults with R/R aggressive B-cell non-Hodgkin lymphoma1,3
  • No Grade 5 CRS or neurologic toxicities in ZUMA-72
  • Both CRS and neurologic toxicities, including fatal or life-threatening reactions, occurred following treatment with YESCARTA1
  • Consider the use of prophylactic corticosteroids in patients after weighing the potential benefits and risks1
  • Authorized Treatment Centers are trained to manage short-term AEs that may occur1

In 2L, most cases of CRS and neurologic toxicities occurred early and resolved within the first few weeks after treatment1

2L CRS with 92% incidence and 7% Grade ≥3 incidence, median 3 days of onset time and 7 days duration

Adverse reactions observed in at least 25% of patients treated with YESCARTA in ZUMA-71

adverse-reaction-1-chart-dsk

aTachycardia includes tachycardia, sinus tachycardia.

bDiarrhea includes diarrhea, colitis.

cFever includes pyrexia.

dFatigue includes fatigue, asthenia, malaise.

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

fEncephalopathy 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.

gHeadache includes headache and tension headache.

hDizziness includes dizziness, dizziness postural, presyncope, syncope, vertigo.

iCough includes cough, productive cough, upper-airway cough syndrome.

jHypotension includes hypotension, capillary leak syndrome, orthostatic hypotension.

In 3L, most cases of CRS and neurologic toxicities occurred early and resolved within the first few weeks after treatment1

3L CRS with 94% incidence and 13% Grade ≥3 incidence, median 3 days onset time and 7 days duration

Adverse reactions observed in at least 25% of patients treated with YESCARTA in ZUMA-11

adverse-reaction-2-chart-dsk

kTachycardia includes tachycardia, sinus tachycardia.

lFever includes fever, febrile neutropenia.

mFatigue includes fatigue, malaise.

nEncephalopathy includes cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, encephalopathy, hypersomnia, leukoencephalopathy, memory impairment, mental status changes, paranoia, somnolence, stupor.

oHeadache includes headache, head discomfort, sinus headache, procedural headache.

pHypoxia includes hypoxia, oxygen saturation decreased.

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

rHypotension includes diastolic hypotension, hypotension, orthostatic hypotension.

In 3L, safety management strategies were specifically developed to help reduce incidence of CRS and neurologic toxicities1

Early and prophylactic use of corticosteroids and/or tocilizumab were evaluated in 2 additional studies in ZUMA-11,6,7

  • Cohort 4: The first subsequent, open label, safety-management study that evaluated the early use of corticosteroids and/or tocilizumab and prophylactic levetiracetam intervention for Grade 1 cytokine release syndrome (CRS) or neurologic toxicity in patients treated with YESCARTA. Median age of patients in Cohort 4: 61 (range: 19-77)1,6
  • Cohort 6: Evaluated the effects of prophylactic corticosteroid and levetiracetam use + earlier corticosteroid and/or tocilizumab intervention. Median age of patients in Cohort 6: 64.5 (range: 37-85)1,7

Please see full study design below.

Graphic showing no Grade 5 CRS or neurologic toxicities in Cohorts 4 and 6
  • 68% of patients in Cohort 6 did not have any CRS or neurologic toxicities in the first 3 days after receiving YESCARTA7
  • Both CRS and neurologic toxicities, including fatal or life-threatening reactions, occurred following treatment with YESCARTA1
  • Most cases of CRS and neurologic toxicities occurred early and resolved within the first few weeks after treatment1
  • Consider the use of prophylactic corticosteroids in patients after weighing the potential benefits and risks1
  • Authorized Treatment Centers are trained to manage short-term AEs that may occur1

Cohorts 4 and 6 also evaluated efficacy in patients treated with early and prophylactic corticosteroids and/or tocilizumab

Similar efficacy results were observed in the clinical trial setting based on the safety management guidelines1,6,7

Cohort 4: Management with early steroid and/or toxilizumab use (73% ORR, 51% CR, median DOR not reached)
  • Response rate and DOR data from the additional safety-management study are descriptive; no formal hypothesis testing was performed, and these data should be carefully interpreted in light of the single-arm design. Efficacy data are not included in the Prescribing Information for YESCARTA1,6
  • Differences in disease characteristics and eligibility criteria between the safety-management study and pivotal trial may have affected outcomes6
  • The safety-management study allowed bridging therapy1,8
  • Response assessment was based on investigator assessment and responses were not confirmed by IRC8
  • Consider the use of prophylactic corticosteroids in patients after weighing the potential benefits and risks1

Study design

Cohort 4: Mangement with early steroids and/or tocilizumab

Cohort 4 study design

  • The first subsequent safety-management, phase 2, multicenter, open-label study evaluating the safety and efficacy of YESCARTA in subjects with R/R LBCL1,7
  • 46 patients with R/R DLBCL, PMBCL, TFL, or HGBCL after ≥2 lines of systemic therapy were enrolled, and 41 were treated with YESCARTA to assess the early use of corticosteroids and/or tocilizumab for Grade 1 CRS or neurologic toxicities1,6
  • Optional bridging chemotherapy was permitted1
    • 28 patients (68%) treated with YESCARTA received bridging therapy between leukapheresis and lymphodepleting chemotherapy
  • Median age of patients in Cohort 4: 61 (range: 19-77)6

Cohort 6: Mangement with prophylactic steroids and/or tocilizumab

Cohort 6 study design

  • A second subsequent open-label, safety-management cohort of 39 patients with LBCL, investigating the effects of prophylactic corticosteroid and levetiracetam use plus earlier corticosteroid and/or tocilizumab intervention on the incidence of CRS and neurologic toxicities in YESCARTA-treated patients with R/R LBCL1,7
  • Response rate and DOR analysis evaluated 40 YESCARTA patients, including 1 patient who only received 1 dose of the 3-day prophylactic regimen of corticosteroids.7 The safety analysis (n=39) consisted of patients who received the full prophylactic treatment with corticosteroids1
  • Following leukapheresis, patients could receive optional bridging therapy per investigator discretion7
    • 53% of patients (21/40) received bridging therapy prior to YESCARTA7
  • The 2-year follow-up analysis reported updated safety outcomes for 40 patients with LBCL in Cohort 6, with a median follow-up time of 26.9 months8*
    • No new CRS events were reported at the 2-year follow-up8
    • 1 patient experienced Grade 5 neurologic toxicity8
  • Median age of patients in Cohort 6: 64.5 (range: 37-85)7

*The 2-year follow-up analysis reported safety outcomes for 40 YESCARTA patients, including 1 patient who received only 1 dose of the 3-day prophylactic regimen of corticosteroids.7,8

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See real-world evidence in patients with R/R LBCL after ≥2 lines of systemic therapy

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2L=second line; 3L=third line; AE=adverse event; CR=complete response; CAR=chimeric antigen receptor; CI=confidence interval; CRS=cytokine release syndrome; DLBCL=diffuse large B-cell lymphoma; DOR=duration of response; ECOG PS=Eastern Cooperative Oncology Group performance status; HDT=high-dose therapy; HGBCL=high-grade B-cell lymphoma; ICU=intensive care unit; IRC=independent review committee; KM=Kaplan-Meier; LBCL=large B-cell lymphoma; NE=not estimable; ORR=objective response rate; PMBCL=primary mediastinal large B-cell lymphoma; R/R=relapsed/refractory; TFL=transformed follicular lymphoma.

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. Kuhnl A, Roddie C, Kirkwood AA, et al. A national service for delivering CD19 CAR-T in large B-cell lymphoma - The UK real-world experience. Br J Haematol. 2022;198(3):492-502. 6. Topp MS, van Meerten T, Houot R, et al. Earlier corticosteroid use for adverse event management in patients receiving axicabtagene ciloleucel for large B-cell lymphoma. Br J Haematol. 2021;195(3):388-398. 7. Oluwole OO, Bouabdallah K, Muñoz J, et al. Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma. Br J Haematol. 2021;194(4):690-700. 8. Oluwole OO, Forcade E, Muñoz J, et al. Long-term outcomes of patients with large B-cell lymphoma treated with axicabtagene ciloleucel and prophylactic corticosteroids. Bone Marrow Transplant. 2024;59(3):366-372.