Safety and management strategies
After your patient receives their YESCARTA infusion, monitoring will take place at the YESCARTA Authorized Treatment Center where there are approved safety protocols and physicians who are specially trained in YESCARTA administration and adverse event management. The YESCARTA Authorized Treatment Center will work with primary hematologists/oncologists to stay connected about treatment decisions, patient progress, and follow-up care. Though infusion and monitoring take place at the treatment center, long-term monitoring should continue in the community setting.
Most cytokine release syndrome and neurologic toxicity events in Cohorts 1 and 2 occurred early, were generally reversible, and were managed per established guidance1,2
Updated safety management study design
- Cohorts 1 and 2: YESCARTA was studied in a phase 2, open-label, single-arm, multicenter trial of 101 adults with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma, comprising the pivotal trial (Cohorts 1 and 2), upon which YESCARTA was FDA approved1,3-5
- Cohort 4: The first subsequent 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 YESCARTA1,4,6
- 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 toxicity on the rate and severity of CRS and neurologic toxicities1,6
- 28 patients (68%) treated with YESCARTA received bridging therapy between leukapheresis and lymphodepleting chemotherapy1
- Cohort 6: A second subsequent open-label, safety-management cohort of 39 patients with LBCL, investigating the effects of prophylactic corticosteroid and levetiracetam use + earlier corticosteroid and/or tocilizumab intervention on the incidence of Grade 1 CRS and neurologic toxicities in YESCARTA-treated patients with R/R LBCL1,4
- Following leukapheresis, patients could receive optional bridging therapy per investigator discretion; 51% of patients (20/39) received bridging therapy prior to YESCARTA7,8
- CRS and neurologic toxicity incidence and severity were assessed in Cohort 67
- 67% of patients (n=26/39) had no CRS or neurologic toxicity events within 72 hours (days 0-3) of YESCARTA infusion9*
*These data are not included in the Prescribing Information for YESCARTA.
Cytokine release syndrome (CRS)
CRS, including fatal or life-threatening reactions, occurred following treatment with YESCARTA.1
There was no incidence of Grade 4 or 5 CRS with updated management strategies (Cohorts 4 and 6)1
Management of CRS
At the Authorized Treatment Center, ensure that 2 doses of tocilizumab are available prior to infusion of YESCARTA. 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. Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension.1
If CRS is suspected, manage according to the recommendations in Section 2.3 of the full Prescribing Information.
| CRS Grade | Tocilizumab | Corticosteroids |
|---|---|---|
| Grade 1 Symptoms require symptomatic treatment only (eg, fever, nausea, fatigue, headache, myalgia, malaise). | If symptoms (eg, fever) not improving after 24 hours, consider managing as Grade 2. | If not improving after 3 days, administer 1 dose of dexamethasone 10 mg intravenously. |
|
Grade 2 Symptoms require and respond to moderate intervention. Oxygen requirement less than 40% FiO2 or hypotension responsive to fluids or low-dose of 1 vasopressor or Grade 2 organ toxicity. |
Administer tocilizumab 8 mg/kg intravenously over 1 hour (not to exceed 800 mg). If no clinical improvement in the signs and symptoms of CRS after the first dose, repeat tocilizumab every 8 hours as needed. Limit to a maximum of 3 doses in a 24-hour period; maximum total of 4 doses. If improving, discontinue tocilizumab. |
Administer dexamethasone 10 mg intravenously once daily. If improving, manage as Grade 1 above and continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as appropriate grade below. |
|
Grade 3 Symptoms require and respond to aggressive intervention. Oxygen requirement greater than or equal to 40% FiO2 or hypotension requiring high-dose or multiple vasopressors or Grade 3 organ toxicity or Grade 4 transaminitis. |
Per Grade 2. If improving, manage as appropriate grade above. |
Dexamethasone 10 mg intravenously 3 times a day. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as Grade 4. |
|
Grade 4 Life-threatening symptoms. Requirements for ventilator support, continuous veno-venous hemodialysis (CVVHD) or Grade 4 organ toxicity (excluding transaminitis). |
Per Grade 2. If improving, manage as appropriate grade above. |
Administer methylprednisolone 1000 mg intravenously once per day for 3 days. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, consider methylprednisolone 1000 mg 2-3 times a day or alternate therapy.† |
†Alternate therapy includes (but is not limited to): anakinra, siltuximab, ruxolitinib, cyclophosphamide, IVIG, and ATG.1
Patients who experience Grade ≥2 CRS (eg, hypotension not responsive to fluids or hypoxia requiring supplemental oxygenation) should be monitored with continuous cardiac telemetry and pulse oximetry. For patients experiencing severe CRS, consider performing an echocardiogram to assess cardiac function. For severe or life-threatening CRS, consider intensive-care supportive therapy.1
Neurologic toxicities
Neurologic toxicities (including immune effector cell-associated neurotoxicity syndrome [ICANS]) that were fatal or life-threatening occurred following treatment with YESCARTA.1
(n=41) Early use View Data
(n=39) Prophylactic use
View Data
| Grade ≥3 incidence 31% | Grade ≥3 incidence 20% | Grade >3 incidence 13% |
| Overall incidence 87% | Overall incidence 78% | Overall incidence 85% |
| Median time to onset 4 DAYS (range 1-43 days) | Median time to onset 6 DAYS (range: 1-93 days) | Median time to onset 6 DAYS (range: 1-274 days) |
| Median duration 17 DAYS | Median duration 8 DAYS (range: 1-144 days) | Median duration 12 DAYS |
|
Management of neurologic toxicities
When managing neurologic toxicity/ICANS at the Authorized Treatment Center, rule out other causes of neurologic symptoms. Patients who experience Grade 2 or higher neurologic toxicities/ICANS should be monitored with continuous cardiac telemetry and pulse oximetry. Provide intensive-care supportive therapy for severe or life-threatening neurologic toxicities. Consider levetiracetam for seizure prophylaxis for any grade of neurologic toxicities.1
See Section 2.3 of the full Prescribing Information for additional monitoring and management guidance relating to neurologic toxicities.
| Grading Assessment‡ | Concurrent CRS | No Concurrent CRS |
|---|---|---|
| Grade 1 |
Administer tocilizumab per CRS Grading and Management table above for management of Grade 1 CRS. In addition, administer 1 dose of dexamethasone 10 mg intravenously. If not improving after 2 days, repeat dexamethasone 10 mg intravenously. |
Administer 1 dose of dexamethasone 10 mg intravenously. If not improving after 2 days, repeat dexamethasone 10 mg intravenously. |
| Consider levetiracetam for seizure prophylaxis. | ||
| Grade 2 |
Administer tocilizumab per CRS Grading and Management table above for management of Grade 2 CRS. In addition, administer dexamethasone 10 mg intravenously 4 times a day. If improving, continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as appropriate grade below. |
Administer dexamethasone 10 mg intravenously 4 times a day. If improving, continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as appropriate grade below. |
| Consider levetiracetam for seizure prophylaxis. | ||
| Grade 3 |
Administer tocilizumab per CRS Grading and Management table above for management of Grade 2 CRS. In addition, administer methylprednisolone 1000 mg intravenously once daily. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, manage as Grade 4. |
Administer methylprednisolone 1000 mg intravenously once daily. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, manage as Grade 4. |
| Consider levetiracetam for seizure prophylaxis. | ||
| Grade 4 |
Administer tocilizumab per CRS Grading and Management table above for management of Grade 2 CRS. In addition, administer methylprednisolone 1000 mg intravenously twice per day. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, consider 1000 mg of methylprednisolone intravenously 3 times a day or alternate therapy.§ |
Administer methylprednisolone 1000 mg intravenously twice per day. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, consider 1000 mg of methylprednisolone intravenously 3 times a day or alternate therapy.§ |
| Consider levetiracetam for seizure prophylaxis. | ||
‡Severity based on Common Terminology Criteria for Adverse Events.1
§Alternate therapy includes (but is not limited to): anakinra, siltuximab, ruxolitinib, cyclophosphamide, IVIG, and ATG.1
Patient monitoring at Authorized Treatment Centers1
Monitoring takes place at the YESCARTA Authorized Treatment Centers where there are approved safety protocols and physicians who are specially trained in YESCARTA administration and adverse event management. Long-term monitoring should continue in the community setting.
7days
Patients will be monitored at least daily for 7 days at the Authorized Treatment Center following infusion for signs and symptoms of CRS and neurologic toxicities.
4weeks
Patients will be instructed to remain within proximity of the Authorized Treatment Center for at least 4 weeks following infusion. Monitor patients for signs or symptoms of CRS or neurologic toxicities for 4 weeks after infusion. Patients will be counseled to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicities occur at any time.
Adverse reactions1
The most common adverse reactions (incidence ≥20%) 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.
Serious adverse reactions occurred in 52% of patients. The most common serious adverse reactions (>2%) included encephalopathy, fever, lung infection, febrile neutropenia, cardiac arrhythmia, cardiac failure, urinary tract infection, renal insufficiency, aphasia, cardiac arrest, Clostridium difficile infection, delirium, hypotension, and hypoxia.
The most common (≥10%) Grade 3 or higher reactions included febrile neutropenia, fever, CRS, encephalopathy, infections with pathogen unspecified, hypotension, hypoxia, and lung infections.
This is not a complete list of adverse events associated with YESCARTA. For additional information, please see Important Safety Information.
| Adverse Reaction | Any grade (%) | Grade ≥3 (%) |
|---|---|---|
| Blood and lymphatic system disorders | ||
| Febrile neutropenia | 34 | 31 |
| Cardiac disorders | ||
| Tachycardiaa | 57 | 2 |
| Arrhythmiab | 23 | 7 |
| Gastrointestinal disorders | ||
| Diarrhea | 38 | 4 |
| Nausea | 34 | 0 |
| Vomiting | 26 | 1 |
| Constipation | 23 | 0 |
| Abdominal painc | 14 | 1 |
| Dry mouth | 11 | 0 |
| General disorders and administration site conditions | ||
| Feverd | 86 | 16 |
| Fatiguee | 46 | 3 |
| Chills | 40 | 0 |
| Edemaf | 19 | 1 |
| Immune system disorders | ||
| Cytokine release syndrome | 94 | 13 |
| Hypogammaglobulinemiag | 15 | 0 |
| Infections and infestations | ||
| Infections with pathogen unspecified | 26 | 16 |
| Viral infections | 16 | 4 |
| Bacterial infections | 13 | 9 |
| Investigations | ||
| Decreased appetite | 44 | 2 |
| Weight decreased | 16 | 0 |
| Dehydration | 11 | 3 |
| Musculoskeletal and connective tissue disorders | ||
| Motor dysfunctionh | 19 | 1 |
| Pain in extremityi | 17 | 2 |
| Back pain | 15 | 1 |
| Muscle pain | 14 | 1 |
| Arthralgia | 10 | 0 |
| Nervous system disorders | ||
| Encephalopathyj | 57 | 29 |
| Headachek | 45 | 1 |
| Tremor | 31 | 2 |
| Dizzinessl | 21 | 1 |
| Aphasiamm | 18 | 6 |
| Psychiatric disorders | ||
| Deliriumn | 17 | 6 |
| Respiratory, thoracic, and mediastinal disorders | ||
| Hypoxiao | 32 | 11 |
| Coughp | 30 | 0 |
| Dyspneaq | 19 | 3 |
| Pleural effusion | 13 | 2 |
| Renal and urinary disorders | ||
| Renal insufficiency | 12 | 5 |
| Vascular disorders | ||
| Hypotensionr | 57 | 15 |
| Hypertension | 15 | 6 |
| Thrombosiss | 10 | 1 |
The following events were also counted in the incidence of CRS: tachycardia, arrhythmia, fever, chills, hypoxia, renal insufficiency, and hypotension.
aTachycardia includes tachycardia and sinus tachycardia.
bArrhythmia includes arrhythmia, atrial fibrillation, atrial flutter, atrioventricular block, bundle branch block right, electrocardiogram QT prolonged, extra-systoles, heart rate irregular, supraventricular extra systoles, supraventricular tachycardia, ventricular arrhythmia, and ventricular tachycardia.
cAbdominal pain includes abdominal pain, abdominal pain lower, and abdominal pain upper.
dFever incudes fever and febrile neutropenia.
eFatigue includes fatigue and malaise.
fEdema includes face edema, generalized edema, local swelling, localized edema, edema, edema genital, edema peripheral, periorbital edema, peripheral swelling, and scrotal edema.
gHypogammaglobulinemia includes hypogammaglobulinemia, blood immunoglobulin D decreased, and blood immunoglobulin G decreased.
hMotor dysfunction includes muscle spasms and muscular weakness.
iPain in extremity includes pain not otherwise specified and pain in extremity.
jEncephalopathy includes cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, encephalopathy, hypersomnia, leukoencephalopathy, memory impairment, mental status changes, paranoia, somnolence, and stupor.
kHeadache includes headache, head discomfort, sinus headache, and procedural headache.
lDizziness includes dizziness, presyncope, and syncope.
mAphasia includes aphasia and dysphasia.
nDelirium includes agitation, delirium, delusion, disorientation, hallucination, hyperactivity, irritability, and restlessness.
oHypoxia includes hypoxia and oxygen saturation decreased.
pCough includes cough, productive cough, and upper-airway cough syndrome.
qDyspnea includes acute respiratory failure, dyspnea, orthopnea, and respiratory distress.
rHypotension includes diastolic hypotension, hypotension, and orthostatic hypotension.
sThrombosis includes deep vein thrombosis, embolism, embolism venous, pulmonary embolism, splenic infarction, splenic vein thrombosis, subclavian vein thrombosis, thrombosis, and thrombosis in device.
DLBCL=diffuse large B-cell lymphoma; HGBCL=high-grade B-cell lymphoma; LBCL=large B-cell lymphoma; PMBCL=primary mediastinal large B-cell lymphoma; R/R=relapsed/refractory; TFL=transformed follicular 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 ≥ 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 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.
INDICATIONMORE
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.
Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.
Please see full Prescribing Information, including BOXED WARNING and Medication Guide.
Authorized Treatment Centers are independent facilities certified to dispense Kite CAR T therapies. Choice of an Authorized Treatment Center is within the sole discretion of the physician and patient. Kite does not endorse any individual treatment sites.
References: 1. YESCARTA® (axicabtagene ciloleucel). Prescribing information. Kite Pharma, Inc; 2022. 2. Data on file. Kite Pharma, Inc; 2018. 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. Oluwole OO, Forcade E, Muñoz J, et al. Prophylactic corticosteroid use with axicabtagene ciloleucel in patients with relapsed/refractory large B-cell lymphoma: one-year follow-up of ZUMA-1 Cohort 6. Presented at: 63rd ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 2832. 5. Locke FL, Ghobadi A, Jacobson CA, et al. 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. 6. Topp MS, van Meerten T, Houot R, et al. Earlier steroid use with axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory large B cell lymphoma. Presented at: 61st ASH Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 243. 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. Data on file [1]. Kite Pharma, Inc; 2022. 9. Data on file [2]. Kite Pharma, Inc; 2022.
