A closer look at who may be appropriate for 2L YESCARTA
CAR T therapy
Information below is not from actual patients and does not encompass all characteristics for YESCARTA eligibility.
Michael, 73 years old:
early relapsed
- Achieved CR in 1L with 6 cycles of R-CHOP
- Relapsed 8 months after
1L chemoimmunotherapy - Stage III DLBCL
- ECOG PS: 0
Mary, 60 years old:
primary refractory*
- Achieved PR as best response
with 6 cycles of R-CHOP - Stage III DLBCL
- ECOG PS: 1
*In ZUMA-7, refractory disease was defined as no CR to 1L therapy.1
NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.
Your role is essential in the YESCARTA treatment journey
Whether it’s before, during, or after treatment, the collaboration between the primary hematologist/oncologist and the YESCARTA Authorized Treatment Center (ATC) is critical to help give your patients the best possible care.
Before
Treatment
(PRIMARY HEM/ONC)
Patient Identification
Early patient identification is critical to patient outcomes.3
It’s important to know when to consider YESCARTA because once a patient has been identified, specialist consultation can begin.
Learn which patient types are potentially eligible for treatment.
Specialist Consultation and Timely Access
Early consultation with a lymphoma specialist at an ATC allows for collective assessment of treatment options.3
Find a YESCARTA ATC to begin the consultation discussion.
If YESCARTA is right for the patient, the ATC may begin treatment.
Collaboration between primary hematologist/oncologist and the ATC ensures the best possible care.
During
Treatment
(ATCs)
Leukapheresis
~3 to 4 hours4: Lymphocytes are collected from the patient and then shipped to the manufacturing site.5
Cell Manufacturing
~18 days*: The patient’s T cells are isolated and engineered ex vivo at a state-of-the-art Kite facility to become CAR T cells.5
*Data reflect results from the ZUMA-7 pivotal trial. The median time from leukapheresis to product delivery.5
Lymphodepleting Chemotherapy
3 days (starting 5 days before YESCARTA infusion): The patient receives a lymphodepleting chemotherapy regimen.5
Infusion
~30 minutes: A single infusion of YESCARTA is administered to the patient at the YESCARTA ATC.5
Monitoring
The patient is monitored at least daily for 7 days by the YESCARTA ATC for signs and symptoms of cytokine release syndrome, neurologic toxicities, and any other side effects.5
For at least 4 weeks after infusion: The patient should stay within 2 hours of the YESCARTA ATC.5,6
After
Treatment
(PRIMARY HEM/ONC)
Ongoing Care and Follow-up
As your patient returns home after their CAR T therapy, they will require your long-term support and ongoing care. Follow-up appointments track the patient’s progress and monitor for adverse reactions. The primary hematologist/oncologist and ATC should remain in contact regarding the patient’s progress.5
For 8 weeks after infusion: the patient should not drive, operate heavy machinery, or do other dangerous things because the treatment can cause sleepiness, confusion, weakness, and temporary memory and coordination problems.5
In addition to other adverse events, monitoring should include5:
- Prolonged cytopenias
- Hypogammaglobulinemia
- Secondary malignancies
- Serious infections
See full Prescribing Information for additional monitoring recommendations.
STEP 1
PROACTIVE PATIENT IDENTIFICATION
PROACTIVE PATIENT IDENTIFICATION IS CRITICAL TO OUTCOMES
While YESCARTA is indicated after 1 line of systemic therapy, you can start identifying and educating your patients proactively in order to accelerate time between potential systemic treatment failure and CAR T treatment.3,5
STEP 2
EARLY SPECIALIST CONSULTATION
CONSULT WITH A CAR T SPECIALIST AT AN AUTHORIZED TREATMENT CENTER THAT MEETS YOUR PATIENT’S NEEDS
Early consultation helps determine if YESCARTA is right for your patient and maximizes their chance at receiving therapy. The optimal time for a consultation may be as soon as first relapse to help ensure optimal access to all available treatment options.3 Consider telemedicine consultations, which may be covered by a patient’s insurance. Always check with the patient’s plan to confirm coverage.
YESCARTA is available only at Authorized Treatment Centers with specialized CAR T healthcare teams trained on how to administer, monitor, and care for patients.5 Choice of an Authorized Treatment Center is within the sole discretion of the treating physician and patient. Kite does not endorse any individual Authorized Treatment Center.
STEP 3
TIMELY ACCESS
MAXIMIZE YOUR PATIENT’S CHANCE AT RECEIVING YESCARTA
As soon as first-line treatment failure or relapse, patients can be evaluated for CAR T therapy at an Authorized Treatment Center. Positioning CAR T treatment later in the disease course runs the risk of patients becoming too frail as the result of advanced disease or side effects of prior treatments.3 Once assessed by the CAR T team, your qualified second-line patients can begin YESCARTA therapy.
Rapid and reliable manufacturing5
- End-to-end manufacturing in the United States
†Two patients received nonconformal products in ZUMA-7 study.5
1L=first line; 2L=second line; 3L=third line; CAR=chimeric antigen receptor; CAR T=chimeric antigen receptor T cell; CR=complete response; DLBCL=diffuse large B-cell lymphoma; ECOG PS=Eastern Cooperative Oncology Group performance status; LBCL=large B-cell lymphoma; NCCN=National Comprehensive Cancer Network; PR=partial response; R-CHOP=rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; R/R=relapsed/refractory.
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. 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. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.2.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed February 8, 2023. To view the most recent and complete version of the guidelines, go online to NCCN.org. 3. Jacobson CA, Farooq U, Ghobadi A. Axicabtagene ciloleucel, an anti-CD-19 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. 4. Roberts ZJ, Better M, Bot A, et al. Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL. Leuk Lymphoma. 2018;59(8):1785-1796. 5. YESCARTA® (axicabtagene ciloleucel). Prescribing information. Kite Pharma, Inc; 2022. 6. YESCARTA® and TECARTUS® REMS Patient Wallet Card. REMS-CTF-0026. April 2021. 7. Data on file. Kite Pharma, Inc; 2022.