"I love YESCARTA® (axicabtagene ciloleucel) is approved in 2 indications | HCP"

2022-06-08 04:27:24

Skip to main content Now approved for adult patients with large B-cell lymphoma that is primary refractory or relapses within 12 months of 1L chemoimmunotherapy For US Healthcare Professionals Indication and Limitations of UsePrescribing Information and Medication GuideImportant Safety InformationREMSFor Patients YESCARTA is approved for: R/R LBCL R/R Large B-Cell Lymphoma R/R Follicular Lymphoma Menu Switch Indication:R/R LBCLR/R FL- - R/R Follicular Lymphoma R/R Large B-Cell Lymphoma HOMEHow YESCARTA WorksCAR T TechnologyMechanism of ActionManufacturing ProcessPATIENT IDENTIFICATIONIdentify Patients EarlyChemo-RefractoryChemo-Nonresponsive (Transplant Intended)Early ASCT RelapseChemo-Insensitive (Transplant Ineligible)Early Relapse (Transplant Ineligible)R/R PMBCLEfficacyZUMA-1 Pivotal TrialResponse RatesDuration of ResponseOverall SurvivalSafety-Management Study DataSafetyCytokine Release Syndrome (CRS)(Pivotal Data and Safety-Management Studies)Neurologic Toxicities(Pivotal Data and Safety-Management Studies)Patient MonitoringAdverse ReactionsTreatment ProcessThe Treatment JourneyPatient IdentificationSpecialist Consultation and Timely AccessLeukapheresisCell ManufacturingLymphodepleting ChemotherapyInfusionMonitoringOngoing Care and Follow-UpGet Your Patient StartedAUTHORIZED TREATMENT CENTERSFind an Authorized Treatment CenterAuthorized Treatment Center Therapy EnrollmentSupport and ResourcesKite Konnect®Coverage SupportResourcesFrequently Asked QuestionsIndication and Limitations of UsePrescribing Information and Medication GuideImportant Safety InformationREMSFor PatientsWhat are you searching for? SINGLE-INFUSION THERAPY FOR ADULTS WITH RELAPSED/REFRACTORY (R/R) LARGE B-CELL LYMPHOMA (LBCL) AFTER ≥2 LINES OF SYSTEMIC THERAPY1 REDEFINE THEIR STORYLINE PIVOTAL ANALYSIS OBJECTIVE RESPONSE RATE 72% ORR1,2 (11.6-month median follow-up; N=101) COMPLETE REMISSION RATE 51% CR1,2 (11.6-month median follow-up; N=101) SINGLE-INFUSION THERAPY FOR ADULTS WITH RELAPSED/REFRACTORY (R/R) LARGE B-CELL LYMPHOMA (LBCL) AFTER ≥2 LINES OF SYSTEMIC THERAPY1 REDEFINE THEIR STORYLINE The tick marks represent censored patients. Patients who have not died by the cutoff date were censored at the last date known to be alive.6 PIVOTAL ANALYSIS OBJECTIVE RESPONSERATE 72% ORR1,2 (11.6-month median follow-up; N=101) COMPLETE REMISSIONRATE 51% CR1,2 (11.6-month median follow-up; N=101) OVERALL SURVIVAL 43% ALIVEAT5YRS3(25.8-month median OS in cohorts 1and2) 43% ALIVE AT5YRS3 OS was a secondary endpoint.4 OS data are descriptive and should be carefully interpreted in light of the single-arm design. OS data are not included in the Prescribing Information (PI) for YESCARTA®. Not all data continued to be captured at the 5-year follow-up. OS, investigator-assessed response, and adverse event reporting were captured.5 The KM estimate of the 5-year OS rate was 43%.3 OVERALL SURVIVAL 43% ALIVEAT5YRS3(25.8‑monthmedianOSincohorts1and2) OS was a secondary endpoint.4 OS data are descriptive and should be carefully interpreted in light of the single-arm design. OS data are not included in the Prescribing Information (PI) for YESCARTA®. Not all data continued to be captured at the 5-year follow-up. OS, investigator-assessed response, and adverse event reporting were captured.5 The KM estimate of the 5-year OS rate was 43%.3 The tick marks represent censored patients. Patients who have not died by the cutoff date were censored at the last date known to be alive.6 KM median OS: 25.8 months (95% CI: 12.8, NE).3 ZUMA-1 was a phase 2, open-label, single-arm, multicenter, pivotal trial in 101 adults with R/R LBCL.1,4,7 For FDA approval, efficacy was established on the basis of CR rate and DOR, as determined by an IRC.1 CR=complete remission; DOR=duration of response; FDA=Food and Drug Administration; IRC=independent review committee; KM=Kaplan-Meier; LBCL=large B-cell lymphoma; NE=not estimable; ORR=objective response rate; OS=overall survival; R/R=relapsed/refractory. ONLY CAR T 3500 + PATIENTSTREATED8* More than 5500 patients with R/R LBCL have already been treated with YESCARTA after ≥2 lines of systemic therapy. *Global commercial and clinical trial data in patients with R/R LBCL after ≥2linesof systemictherapy as of September,29,2021.8 Choose a YESCARTA Authorized Treatment Center Maximize your patient’s chance at receiving CART therapy by speaking with a YESCARTA Authorized Treatment Center for early consult, evaluation, and preparation. Find a treatment center CONNECT YOUR PATIENTS TO YESCARTA PROACTIVE PATIENT IDENTIFICATION PROACTIVE PATIENT IDENTIFICATIONIS CRITICAL TO OUTCOMES Start identifying and educatingyour patients proactively.9 Identify patients EARLY SPECIALISTCONSULTATION CONSULT WITH A CAR T SPECIALIST ATTHE AUTHORIZED TREATMENT CENTERTHAT MEETS YOUR PATIENT’S NEEDS The optimal time for a consultation may be as soon as first relapse for potential third-line candidacy.9 Find a treatment center TIMELYACCESS MAXIMIZE YOUR PATIENT’S CHANCEAT RECEIVING YESCARTA Once assessed by the CAR T team, your qualified third-line patients can begin YESCARTA therapy.1 See the process Live National Broadcast program about the new indication. Sign up. Broadcast Registration In light of COVID-19, we remain committed to delivering YESCARTA to patients safely, rapidly, and reliably. There is currently no supply disruption. Learn about our ongoing COVID-19 response. COVID-19 Update WHAT IS YESCARTA? Find out what CAR T therapy is and how YESCARTA works. FIND OUT WHO IS RIGHT FOR YESCARTA? Learn about the variety of patient types potentially eligible for YESCARTA. LEARN MORE HOW WAS THE PIVOTAL TRIAL DESIGNED? Read about the ZUMA-1 pivotal trial in adult patients with relapsed/refractory large B-cell lymphoma. READ MORE HOW DO I GET MY PATIENT STARTED? Find a YESCARTA Authorized Treatment Center to begin your patient’s YESCARTAjourney. LEARN HOW INDICATIONS 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. 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 ≥Grade3 in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including ≥Grade3 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 2days following infusion (range: 1-12days) and the median duration was 7days (range: 2-58days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3days following infusion (range: 1-10days) and the median duration was 7days (range: 2-43days). CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade3 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 4days (range: 1-20days) and median duration was 6days (range: 1-27days) 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 2days (range: 1-8days) and the median duration of CRS was 7days (range: 2-16days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3days 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 5days (range: 1-15days) and the median duration of CRS was 4days (range: 1-10days). 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 7days 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 4days (range: 1-43days) and the median duration was 17days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5days (range: 1-133days) and median duration was 15days 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 6days (range: 1-79days) and the median duration was 16days. 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 7days 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 173days 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 6days (range: 1-93days) with a median duration of 8days (range: 1-144days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3days 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 6days (range: 1-274days) with a median duration of 12days (range: 1-107days). 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 7days 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 MALIGNANCIESSecondary 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 MACHINESDue 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. Please see accompanying full Prescribing Information, including BOXED WARNING and Medication Guide. INDICATIONS 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. 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 ≥Grade3 in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including ≥Grade3 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 2days following infusion (range: 1-12days) and the median duration was 7days (range: 2-58days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3days following infusion (range: 1-10days) and the median duration was 7days (range: 2-43days). CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade3 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 4days (range: 1-20days) and median duration was 6days (range: 1-27days) 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 2days (range: 1-8days) and the median duration of CRS was 7days (range: 2-16days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3days 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 5days (range: 1-15days) and the median duration of CRS was 4days (range: 1-10days). 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 7days 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 4days (range: 1-43days) and the median duration was 17days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5days (range: 1-133days) and median duration was 15days 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 6days (range: 1-79days) and the median duration was 16days. 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 7days 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 173days 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 6days (range: 1-93days) with a median duration of 8days (range: 1-144days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3days 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 6days (range: 1-274days) with a median duration of 12days (range: 1-107days). 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 7days 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 MALIGNANCIESSecondary 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 MACHINESDue 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. Please see accompanying full Prescribing Information, including BOXED WARNING and Medication Guide. INDICATIONS 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. 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 ≥Grade3 in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including ≥Grade3 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 2days following infusion (range: 1-12days) and the median duration was 7days (range: 2-58days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3days following infusion (range: 1-10days) and the median duration was 7days (range: 2-43days). CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade3 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 4days (range: 1-20days) and median duration was 6days (range: 1-27days) 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 2days (range: 1-8days) and the median duration of CRS was 7days (range: 2-16days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3days 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 5days (range: 1-15days) and the median duration of CRS was 4days (range: 1-10days). 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 7days 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 4days (range: 1-43days) and the median duration was 17days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5days (range: 1-133days) and median duration was 15days 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 6days (range: 1-79days) and the median duration was 16days. 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 7days 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 173days 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 6days (range: 1-93days) with a median duration of 8days (range: 1-144days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3days 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 6days (range: 1-274days) with a median duration of 12days (range: 1-107days). 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 7days 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 MALIGNANCIESSecondary 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 MACHINESDue 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. Please see accompanying 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.LockeFL, GhobadiA, JacobsonCA, etal. Durability of response in ZUMA-1, the pivotal phase 2 study of axicabtagene ciloleucel (Axi-Cel) in patients (Pts) with refractory large B-cell lymphoma. Presented at: 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL. Abstract 3003. 3.Data on file [1]. Kite Pharma, Inc; 2021. 4.LockeFL, GhobadiA, JacobsonCA, etal. 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. 5.Data on file [1]. Kite Pharma, Inc; 2019. 6.Data on file [2]. Kite Pharma, Inc; 2019. 7.Neelapu SS, Jacobson CA, Oluwole OO, et al. Outcomes of older patients in ZUMA-1, a pivotal study of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2020;135(23):2106-2109. 8.Data on file [2]. Kite Pharma, Inc; 2021. 9.Jacobson CA, Farooq U, Ghobadi A. Axicabtagene ciloleucel, an anti-CD19 chimeric antigen receptor T-cell therapy for relapsed or refractory large B-cell lymphoma: practical implications for the community oncologist. Oncologist. 2020;25(1):e138-e146. doi:10.1634/theoncologist.2019-0395 Terms and ConditionsPrivacy PolicyContact UsSite MapSite MapThis website is intended for US healthcare professionals only. The content on this site may not apply to non-US audiences as regulatory control, legal requirements, and/or medical practices may vary in other countries.YESCARTA, the Yescarta Logo, TECARTUS, KITE KONNECT, the Kite Konnect Logo, KITE, and the Kite Logo are trademarks of Kite Pharma, Inc.GILEAD is a trademark of Gilead Sciences, Inc.All other trademarks referenced herein are the property of their respective owners.© 2022 Kite Pharma, Inc. All rights reserved. | US-YESP-0126 04/2022 You are now leaving YESCARTAHCP.com. The National Broadcast program is intended for US healthcare professionals only. Select CANCEL to return or CONTINUE to proceed. Cancel Continue