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Yescarta is a brand name for Axicabtagene Ciloleucel. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Yescarta is indicated for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy. Yescarta is indicated for the treatment of adult patients with relapsed or…
Verbatim from this product's EMA label. Tap a section to expand.
Yescarta must be administered in a qualified treatment centre by a physician with experience in the treatment of haematological malignancies and trained for administration and management of patients treated with the medicinal product.
In the event of cytokine release syndrome (CRS), at least 1 dose of tocilizumab, and emergency equipment must be available prior to infusion. The qualified treatment centre must have access to an additional dose of tocilizumab within 8 hours of each previous dose.
In the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, suitable alternative measures to treat CRS instead of tocilizumab must be available prior to infusion.
4). Treatment consists of a single dose for infusion containing a dispersion for infusion of CAR-positive viable T cells in one infusion bag. The target dose is 2 × 106 CAR-positive viable T cells per kg of body weight (within a range of 1 × 106 – 2 × 106 cells/kg), with a maximum of 2 × 108 CAR-positive viable T cells for patients 100 kg and above.
e. date of product availability for shipment). Pre-treatment (lymphodepleting chemotherapy) • A lymphodepleting chemotherapy regimen consisting of cyclophosphamide 500 mg/m2 intravenously and fludarabine 30 mg/m2 intravenously must be administered prior to infusing Yescarta.
The recommended days are on the 5th, 4th, and 3rd day before infusion of Yescarta. 5 to 25 mg intravenously or orally, or equivalent medicinal products, be administered approximately 1 hour before the infusion of Yescarta to reduce the possibility of an infusion reaction.
5). Prophylactic use of systemic corticosteroids may be considered in patients at increased risk of severe immune-mediated adverse reactions, if the potential benefit outweighs the risk and as guided by local institutional and/or national or European/international guidelines.
Monitoring • Patients must be monitored daily for the first 7 days following infusion for signs and symptoms of potential CRS, neurologic events and other toxicities. Physicians can consider hospitalisation for the first 7 days or at the first signs or symptoms of CRS and/or neurologic events.
• After the first 7 days following the infusion, the patient is to be monitored at the physician’s discretion for at least an additional 7 days. • Patients must remain within proximity of a qualified treatment centre or appropriately trained clinical facility for at least 2 weeks following infusion.
Summary of the safety profile The safety data described in this section are from a total of 397 adult patients treated with Yescarta in three multi-centre pivotal clinical studies (ZUMA-1, ZUMA-5 and ZUMA-7) and post-marketing experience.
Adverse reactions are adverse events from pivotal clinical studies and post-marketing experience medically assessed as reasonably attributed to axicabtagene ciloleucel. Relapsed or refractory DLBCL, PMBCL and DLBCL arising from follicular lymphoma after two or more lines of systemic therapy Safety data from ZUMA-1 reflects exposure to Yescarta in a Phase 1/2 study in which 108 patients received CAR-positive T cells based on a recommended dose which was weight-based.
2 months). The most significant and frequently occurring adverse reactions were CRS (93%), encephalopathy (60%), and infections (40%). Serious adverse reactions occurred in 51% of patients. The most common (≥ 5%) serious adverse reactions included encephalopathy (22%), unspecified pathogen infections (15%), bacterial infection (6%), viral infection (6%), febrile neutropenia (5%), and fever (5%).
The most common (≥ 5%) Grade 3 or higher non-haematological adverse reactions included encephalopathy (31%), unspecified pathogen infections (19%), CRS (11%), bacterial infection (9%), delirium (6%), hypertension (6%), hypotension (6%), transaminases increased (6%), and viral infection (6%).
The most common Grade 3 or higher haematological adverse reactions included lymphopenia (99%), leukopenia (96%), neutropenia (94%), anaemia (65%), and thrombocytopenia (56%). DLBCL and HGBL that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy Safety data from ZUMA-7 reflects exposure to Yescarta in a Phase 3 study in which 170 patients received CAR-positive T cells based on a recommended dose which was weight-based.
Traceability The traceability requirements of cell-based advanced therapy medicinal products must apply. To ensure traceability the name of the product, the batch number and the name of the treated patient must be kept for a period of 30 years after expiry date of the medicinal product.
5 Autologous use Yescarta is intended solely for autologous use and must not, under any circumstances, be administered to other patients. Before infusion, the patient’s identity must match the patient identifiers on the Yescarta infusion bag and cassette.
Yescarta must not be administered if the information on the patient-specific infusion bag and cassette label does not match the patient’s identity. General Warnings and precautions of lymphodepleting chemotherapy must be considered.
Reasons to delay treatment Due to the risks associated with Yescarta treatment, infusion must be delayed if a patient has any of the following conditions: • Unresolved serious adverse reactions (especially pulmonary reactions, cardiac reactions, or hypotension) including from preceding chemotherapies.
• Active uncontrolled infection. • Active graft-versus-host disease (GvHD). In some cases, the treatment may be delayed after administration of the lymphodepleting chemotherapy regimen. 2) Monitoring after infusion Patients must be monitored daily for the first 7 days following infusion for signs and symptoms of potential CRS, neurologic events and other toxicities.
Physicians can consider hospitalisation for the first 7 days or at the first signs or symptoms of CRS and/or neurologic events. After the first 7 days following infusion, the patient is to be monitored at the physician’s discretion for at least an additional 7 days.
Patients and caregivers should be informed about the potential late onset of CRS or neurologic events and instructed to seek immediate medical attention if patients experience any signs or symptoms of CRS or neurologic events. Patients must remain within proximity of a qualified treatment centre or appropriately trained clinical facility for at least 2 weeks following infusion and seek immediate medical attention should signs or symptoms of CRS or neurological adverse reactions occur.
1 or to gentamicin (a possible trace residue). Contraindications of the lymphodepleting chemotherapy must be considered.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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4 Special populations Patients with human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infection There is limited clinical experience in patients with active HIV, HBV or HCV infection. Elderly No dose adjustment is required in patients ≥ 65 years of age.
Paediatric population The safety and efficacy of Yescarta in children and adolescents below 18 years of age have not yet been established. No data are available. Method of administration Yescarta is to be administered via intravenous infusion.
Yescarta must not be irradiated. A leukodepleting filter must not be used. Before administration, it must be confirmed that the patient’s identity matches the unique patient information on the Yescarta infusion bag and cassette. Administration • A leukodepleting filter must not be used.
• Tocilizumab and emergency equipment must be available prior to infusion and during the monitoring period. In the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, suitable alternative measures to treat CRS instead of tocilizumab must be available prior to infusion.
• Yescarta is intended for autologous use only, it must be confirmed that the patient’s identity matches the patient identifiers on the Yescarta infusion bag. • Once the tubing has been primed, the entire content of the Yescarta infusion bag must be infused within 30 minutes by either gravity or a peristaltic pump.
6.
3 months). The most significant and frequently occurring adverse reactions were CRS (92%), encephalopathy (49%), and infections (45%). Serious adverse reactions occurred in 54% of patients. The most common (≥ 5%) serious adverse reactions included CRS (17%), encephalopathy (16%), unspecified pathogen infections (8%), fever (6%) and viral infection (5%).
The most common (≥ 5%) Grade 3 or higher non-haematological adverse reactions included encephalopathy (19%), unspecified pathogen infections (8%), CRS (6%), and bacterial infection (5%). The most common Grade 3 or higher haematological adverse reactions included lymphopenia (99%), leukopenia (95%), neutropenia (94%), anaemia (41%), and thrombocytopenia (26%).
Follicular lymphoma after three or more lines of systemic therapy Safety data from ZUMA-5 reflects exposure to Yescarta in a Phase 2 study in which 119 patients with relapsed/refractory FL, received CAR-positive T cells based on a recommended dose which was weight-based.
3 months). The most significant and frequently occurring adverse reactions were CRS (77%), infections (59%), and encephalopathy (47%). 11 Serious adverse reactions occurred in 45% of patients. The most common (≥ 5%) serious adverse reactions included encephalopathy (16%), unspecified pathogen infections (12%), CRS (12%), and bacterial infection (5%).
The most common (≥ 5%) Grade 3 or higher non-haematological adverse reactions included encephalopathy (14%), unspecified pathogen infections (11%), CRS (6%), and bacterial infection (5%). The most common Grade 3 or higher haematological adverse reactions included lymphopenia (99%), leukopenia (94%), neutropenia (92%), thrombocytopenia (34%), and anaemia (33%).
Tabulated list of adverse reactions Adverse reactions described in this section were identified in patients exposed to Yescarta in ZUMA-1 (n=108), ZUMA-5 (n=119), and ZUMA-7 (n=170) and from post-marketing reports. These reactions are presented by system organ class and by frequency.
Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥1/10 000 to < 1/1 000). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Table 1:
Adverse drug reactions identified with Yescarta System Organ Class (SOC) Frequency Adverse reactions Infections and infestations Very common Unspecified pathogen infections Viral infection Bacterial infection Common Fungal infection Neoplasms benign, malignant and unspecified (including cysts and polyps) Uncommon Secondary malignancy of T-cell origin Blood and lymphatic system disorders Very common Febrile neutropenia# Neutropenia# Lymphopenia# Leukopenia# Anaemia# Thrombocytopenia# Common Coagulopathya Immune system disorders Very common Cytokine Release Syndrome Immunoglobulins decreasedb Common Hypersensitivity Uncommon Haemophagocytic lymphohistiocytosis* Metabolism and nutrition disorders Very common Hyponatraemia# Hypophosphataemia# Hyperuricemia#** Hyperglycaemia# Decreased appetitec Common Hypokalaemia# Hypocalcaemia# Hypoalbuminaemia# Dehydrationd Weight decreased Psychiatric disorders Very common Deliriume Insomnia Common Anxiety Affective disorderf 12 System Organ Class (SOC) Frequency Adverse reactions Nervous system disorders Very common Encephalopathyg Tremorh Headachei Dizzinessj Common Ataxiak Seizures, including status epilepticus Hemiparesis Facial paralysisl Neuropathy peripheralm Myoclonus Uncommon Quadriplegia Spinal cord oedema Myelitis Dyscalculia Eye disorders Common Visual impairmentn Cardiac disorders Very common Tachycardiao Arrhythmiap Common Cardiac arrest Cardiac failureq Vascular disorders Very common Hypotensionr Hypertension […]
If the post-infusion monitoring of patients takes place in an appropriately trained clinical facility that is not the treatment center, it must meet the same requirements as the qualified treatment centre regarding the availability of emergency equipment and tocilizumab.
Vital signs and organ function must be monitored depending on the severity of the reaction. Transmission of an infectious agent Although Yescarta is tested for sterility and mycoplasma, a risk of transmission of infectious agents exists.
Healthcare professionals administering Yescarta must, therefore, monitor patients for signs and symptoms of infection after treatment and treat appropriately, if needed. 2). 6 Blood, organ, tissue and cell donation Patients treated with Yescarta must not donate blood, organs, tissues, or cells for transplantation.
Concomitant disease Patients with active central nervous system (CNS) disorder or inadequate renal, hepatic, pulmonary, or cardiac function are likely to be more vulnerable to the consequences of the adverse reactions described below and require special attention.
Primary CNS lymphoma There is no experience of use of Yescarta in patients with primary CNS lymphoma. Therefore, the risk/benefit of Yescarta has not been established in this population. Cytokine release syndrome Nearly all patients experienced some degree of CRS.
8). Diagnosis of CRS requires excluding alternate causes of systemic inflammatory response, including infection. Management of cytokine release syndrome associated with Yescarta At least 1 dose per patient of tocilizumab, an interleukin 6 (IL 6) receptor inhibitor, must be on site and available for administration prior to Yescarta infusion.
The qualified treatment centre must have access to an additional dose of tocilizumab within 8 hours of each previous dose. If the post-infusion monitoring of patients takes place in an appropriately trained clinical facility, it must also adhere to the same requirements regarding the availability of tocilizumab.
In the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicine Agency shortage catalogue, the treatment centre /clinical facility must have access to suitable alternative measures instead of tocilizumab to treat CRS.
The management of patients should be conducted based on the patient’s clinical presentation and in accordance with applicable local institutional and/or national or European/international clinical guidelines. Physicians are advised to exercise clinical judgment consistent with these standards.
Yescarta must not be administered to patients with active infections or inflammatory disease until these conditions have resolved. , hepatic, renal, cardiac, and pulmonary). In addition, worsening of underlying organ pathologies can occur in the setting of CRS.
Patients with medically significant cardiac dysfunction must be managed by standards of critical care and measures such as echocardiography are to be considered. Evaluation for haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) is to be considered in patients with severe or unresponsive CRS.
HLH/MAS should be managed […]