YESCARTA logo and TECARTUS logo

Risk Evaluation and Mitigation Strategy (REMS)

What Is the YESCARTA and TECARTUS REMS Program?

A REMS is a program required by the United States (US) Food and Drug Administration (FDA). The FDA has determined that a REMS is necessary to ensure that the benefits of YESCARTA and TECARTUS outweigh the risks of cytokine release syndrome and neurologic toxicities. YESCARTA and TECARTUS are available only through the YESCARTA and TECARTUS REMS Program.

YESCARTA logo
TECARTUS logo

BOXED WARNING FOR YESCARTA

Cytokine Release Syndrome

  • Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with YESCARTA
  • CRS occurred in 94% (101/108) of patients with large B-cell lymphoma (LBCL) in ZUMA-1, including ≥ Grade 3 CRS in 13%
  • CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 CRS in 8% (11/146) of patients with iNHL
  • The median time to onset of CRS was 2 days (range: 1-12 days) for patients with LBCL and 4 days (range: 1-20 days) for patients with iNHL
  • The median duration of CRS was 7 days (range: 2-58 days) for patients with LBCL and 6 days (range: 1-27 days) for patients with iNHL
  • Among patients who died after receiving YESCARTA, 4 patients with LBCL and 1 patient with iNHL had ongoing CRS events at the time of death
  • Key manifestations of CRS (≥10%) in all patients combined include fever (80%), hypotension (38%), tachycardia (29%), hypoxia (21%), chills (21%), and headache (13%)
  • Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)
  • In a subsequent cohort of LBCL patients, tocilizumab and/or corticosteroids were administered for ongoing Grade 1 events
    • CRS occurred in 93% (38/41) of these patients and 2% (1/41) had Grade 3 CRS, with no patients experiencing a Grade 4 or 5 event
    • The median time to onset of CRS was 2 days (range: 1-8 days)
    • The median duration of CRS was 7 days (range: 2-16 days)
    • Key manifestations of CRS (>5%) included pyrexia, hypotension, chills, headache, nausea, tachycardia, C-reactive protein increased, fatigue, hypoxia, and vomiting

Neurologic Toxicities

  • Neurologic toxicities that were fatal or life-threatening occurred following treatment with YESCARTA
  • Neurologic toxicities occurred in 87% (94/108) of patients with LBCL, including ≥ Grade 3 cases in 31%
  • Neurologic toxicities occurred in 77% (112/146) of patients with iNHL, including ≥ Grade 3 in 21%
  • Neurologic toxicities occurred within the first 7 days of YESCARTA infusion for 89% of affected patients with LBCL and 74% of affected patients with iNHL
  • The median time to onset was 4 days (range: 1-43 days) for patients with LBCL and 6 days (range: 1-79 days) for patients with iNHL
  • The median duration was 17 days in patients with LBCL and 16 days in patients with iNHL
  • The most common neurologic toxicities (≥10%) in all patients combined included encephalopathy (53%), headache (45%), tremor (31%), dizziness (20%), delirium (16%), aphasia (15%), and insomnia (11%)
  • In a subsequent cohort of LBCL patients who received corticosteroids at the onset of Grade 1 toxicities
    • Neurologic toxicities occurred in 78% (32/41) of these patients and 20% (8/41) had Grade 3 neurologic toxicities with no patients experiencing a Grade 4 or 5 event
    • The median time to onset of neurologic toxicities was 6 days (range: 1-93 days)
    • The median duration was 8 days (range: 1-144 days)
    • The most common neurologic toxicities were consistent with the overall LBCL population treated with YESCARTA
  • Prolonged encephalopathy lasting up to 173 days was noted
  • Serious events including leukoencephalopathy and seizures occurred with YESCARTA
  • Fatal and serious cases of cerebral edema have occurred in patients treated with YESCARTA

YESCARTA AND TECARTUS REMS PROGRAM REQUIREMENTS

Hospitals and their associated clinics must be enrolled in the YESCARTA and TECARTUS REMS Program to be able to dispense YESCARTA and/or TECARTUS.

All relevant staff involved in the prescribing, dispensing, or administering of YESCARTA and/or TECARTUS are trained on the YESCARTA and TECARTUS REMS Program requirements, and must successfully complete a YESCARTA and TECARTUS REMS Program Knowledge Assessment.

Hospital Enrollment Instructions

An authorized representative must enroll in the YESCARTA and TECARTUS REMS Program on behalf of the hospital and its associated clinics. To be enrolled in the YESCARTA and TECARTUS REMS Program, the representative must:

  1. Complete the training program, which includes review of:
    • YESCARTA and TECARTUS full Prescribing Information
    • YESCARTA and TECARTUS REMS Program Training
    • YESCARTA and TECARTUS Adverse Reaction Management Guide
  2. Successfully complete the YESCARTA and TECARTUS REMS Program Knowledge Assessment.
  3. Complete the YESCARTA and TECARTUS REMS Program Hospital Enrollment Form.
  4. Oversee implementation and compliance with the YESCARTA and TECARTUS REMS Program requirements:
    • Ensure that all relevant staff involved in the prescribing, dispensing, or administering of YESCARTA and/or TECARTUS are trained on the REMS Program requirements and successfully complete the YESCARTA and TECARTUS REMS Program Knowledge Assessment. The authorized representative will determine relevant staff who require training
    • Maintain training records of staff
    • Ensure that the hospital and its associated clinics have a minimum of 2 doses of tocilizumab available on-site for each patient and are ready for immediate administration (within 2 hours)
    • Prior to patient discharge, provide patients/caregivers with the Patient Wallet Card and instruct patient to remain within close proximity (within 2 hours) of the certified administering hospital and its associated clinics for at least 4 weeks following YESCARTA or TECARTUS infusion
    • Put processes and procedures in place to ensure that relevant new staff are trained, and relevant staff are retrained if YESCARTA or TECARTUS has not been dispensed at least once annually from the date of certification in the YESCARTA and TECARTUS REMS Program

Indication

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

  • 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.
    Limitation of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.
  • Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

BOXED WARNING FOR TECARTUS

Cytokine Release Syndrome

  • Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with TECARTUS
  • CRS occurred in 91% (75/82) of patients with MCL, including ≥ Grade 3 (Lee grading system1) CRS in 18% of patients. CRS occurred in 92% (72/78) of patients with ALL, including ≥ Grade 3 (Lee grading system1) CRS in 26% of patients
  • Among the patients with MCL who died after receiving TECARTUS, one had a fatal CRS event. Three patients with ALL had ongoing CRS events at the time of death
  • The median time to onset of CRS was 3 days (range: 1-13 days), and the median duration of CRS was 10 days (range: 1-50 days) for patients with MCL. The median time to onset of CRS was 5 days (range: 1-12 days) and the median duration of CRS was 8 days (range: 2-63 days) for patients with ALL
  • Key manifestations of CRS (>10%) were similar in MCL and ALL and included fever (93%), hypotension (62%), tachycardia (59%), chills (32%), hypoxia (31%), headache (21%), fatigue (20%), and nausea (13%)
  • Serious events associated with CRS in MCL and ALL combined (≥2%) included hypotension, fever, hypoxia, tachycardia, and dyspnea

1Lee DW et al (2014). Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 Jul 10; 124(2): 188-195.

Neurologic Toxicities

  • Neurologic events, including those that were fatal or life-threatening, occurred following treatment with TECARTUS
  • The median time to onset for neurologic events was 6 days (range: 1-32 days) with a median duration of 21 days (range: 2-454 days) in patients with MCL. The median time to onset for neurologic events was 7 days (range: 1-51 days) with a median duration of 15 days (range: 1-397 days) in patients with ALL
  • Neurologic events occurred in 81% (66/82) of patients with MCL, including ≥ Grade 3 in 37% of patients. Neurologic events occurred in 87% (68/78) of patients with ALL, including ≥ Grade 3 in 35% of patients
  • Nine patients (3 patients with MCL and 6 patients with ALL) had ongoing neurologic events at the time of death
  • Neurologic events resolved for 119 out of 134 (89%) of all patients treated with TECARTUS
  • Ninety-one percent of all treated patients experienced the first CRS or neurological event within the first 7 days after TECARTUS infusion
  • The most common neurologic events (>10%) were similar in MCL and ALL and included encephalopathy (57%), headache (37%), tremor (34%), confusional state (26%), aphasia (23%), delirium (17%), dizziness (15%), anxiety (14%), and agitation (12%)
  • Serious events (≥ 2%) including encephalopathy, aphasia, confusional state, and seizures occurred after treatment with TECARTUS

YESCARTA AND TECARTUS REMS PROGRAM REQUIREMENTS

Hospitals and their associated clinics must be enrolled in the YESCARTA and TECARTUS REMS Program to be able to dispense YESCARTA and/or TECARTUS.

All relevant staff involved in the prescribing, dispensing, or administering of YESCARTA and/or TECARTUS are trained on the YESCARTA and TECARTUS REMS Program requirements, and must successfully complete a YESCARTA and TECARTUS REMS Program Knowledge Assessment.

Hospital Enrollment Instructions

An authorized representative must enroll in the YESCARTA and TECARTUS REMS Program on behalf of the hospital and its associated clinics. To be enrolled in the YESCARTA and TECARTUS REMS Program, the representative must:

  1. Complete the training program, which includes review of:
    • YESCARTA and TECARTUS full Prescribing Information
    • YESCARTA and TECARTUS REMS Program Training
    • YESCARTA and TECARTUS Adverse Reaction Management Guide
  2. Successfully complete the YESCARTA and TECARTUS REMS Program Knowledge Assessment.
  3. Complete the YESCARTA and TECARTUS REMS Program Hospital Enrollment Form.
  4. Oversee implementation and compliance with the YESCARTA and TECARTUS REMS Program requirements:
    • Ensure that all relevant staff involved in the prescribing, dispensing, or administering of YESCARTA and/or TECARTUS are trained on the REMS Program requirements and successfully complete the YESCARTA and TECARTUS REMS Program Knowledge Assessment. The authorized representative will determine relevant staff who require training
    • Maintain training records of staff
    • Ensure that the hospital and its associated clinics have a minimum of 2 doses of tocilizumab available on-site for each patient and are ready for immediate administration (within 2 hours)
    • Prior to patient discharge, provide patients/caregivers with the Patient Wallet Card and instruct patient to remain within close proximity (within 2 hours) of the certified administering hospital and its associated clinics for at least 4 weeks following YESCARTA or TECARTUS infusion
    • Put processes and procedures in place to ensure that relevant new staff are trained, and relevant staff are retrained if YESCARTA or TECARTUS has not been dispensed at least once annually from the date of certification in the YESCARTA and TECARTUS REMS Program

Indication

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

  • Adult patients with relapsed or refractory mantle cell lymphoma (MCL). This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
  • Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).