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Tecartus is a brand name for Brexucabtagene Autoleucel. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Mantle cell lymphoma Tecartus is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after two or more lines of systemic therapy including a Bruton’s tyrosine kinase (BTK) inhibitor. Acute lymphoblastic leukaemia Tecartus is indicated for the treatment of adult patients…
Verbatim from this product's EMA label. Tap a section to expand.
Tecartus 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 Tecartus. At least 1 dose of tocilizumab for use in the event of cytokine release syndrome (CRS) 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). Mantle cell lymphoma 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 (range: 1 × 106–2 × 106 cells/kg), with a maximum of 2 × 108 CAR-positive viable T cells for patients 100 kg and above.
Tecartus is recommended to be infused 3 to 14 days after completion of the lymphodepleting chemotherapy for MCL patients. e. date of product availability for shipment). Pre-treatment (lymphodepleting chemotherapy) for MCL patients • A lymphodepleting chemotherapy regimen consisting of cyclophosphamide 500 mg/m² intravenously and fludarabine 30 mg/m² intravenously must be administered prior to infusing Tecartus.
The recommended days are on the 5th, 4th, and 3rd day before infusion of Tecartus. Acute lymphoblastic leukaemia 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 1 × 106 CAR-positive viable T cells per kg of body weight, with a maximum of 1 × 108 CAR-positive viable T cells for patients 100 kg and above. Tecartus is recommended to be infused 2 to 14 days after completion of the lymphodepleting chemotherapy for ALL patients.
e. date of product availability for shipment). 4 Pre-treatment (lymphodepleting chemotherapy) for ALL patients A lymphodepleting chemotherapy regimen consisting of cyclophosphamide 900 mg/m2 intravenously over 60 minutes must be administered prior to infusing Tecartus.
5 × 106 anti-CD19 CAR T cells/kg) based on a recommended dose which was weight-based. The most significant and frequently occurring adverse reactions were CRS (91%), infections (55%) and encephalopathy (51%). Serious adverse reactions occurred in 56% of patients.
The most common serious adverse reactions included encephalopathy (26%), infections (28%) and cytokine release syndrome (15%). Grade 3 or higher adverse reactions were reported in 67% of patients. The most common Grade 3 or higher non-haematological adverse reactions included infections (34%) and encephalopathy (24%).
The most common Grade 3 or higher haematological adverse reactions included neutropenia (99%), leukopenia (98%), lymphopenia (96%), thrombocytopenia (65%) and anaemia (56%). 5 × 106, 1 × 106, or 2 × 106 anti-CD19 CAR T cells/kg) based on a recommended dose which was weight based.
The most significant and frequently occurring adverse reactions were CRS (91%), encephalopathy (57%), and infections (41%). Serious adverse reactions occurred in 70% of patients. The most common serious adverse reactions included CRS (25%), infections (22%) and encephalopathy (21%).
Grade 3 or higher adverse reactions were reported in 76% of patients. The most common Grade 3 or higher non-haematological adverse reactions included infections (27%), CRS (25%) and encephalopathy (22%). Tabulated list of adverse reactions Adverse reactions described in this section were identified in a total of 182 patients exposed to Tecartus in two multi-centre pivotal clinical studies, ZUMA-2 (n=82) and ZUMA-3 (n=100).
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). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
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.
Autologous use Tecartus 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 Tecartus infusion bag and cassette.
Do not infuse Tecartus if the information on the patient-specific cassette label does not match the intended patient’s identity. General Warnings and precautions of lymphodepleting chemotherapy must be considered. Reasons to delay treatment Due to the risks associated with Tecartus 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 or inflammatory disease. • 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 6 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. 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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This is recommended on the 2nd day before infusion of Tecartus. Fludarabine 25 mg/m2 intravenously over 30 minutes must be administered prior to infusing Tecartus. The recommended days are on the 4th, 3rd, and 2nd day before infusion of Tecartus.
5 to 25 mg intravenously or orally (or equivalent medicinal products) approximately 1 hour before the infusion of Tecartus. 5). Prophylactic use of systemic corticosteroids may be considered in patients at increased risk of severe immune-mediated adverse reactions, only if the potential benefit outweighs the risk and as guided by local institutional and/or national or European/international guidelines.
4- Reasons to delay treatment). 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 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.
Special populations Elderly No dose adjustment is required in patients ≥65 years of age. Patients seropositive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) There is no experience with manufacturing Tecartus for patients with a positive test for HIV, active HBV, or active HCV infection.
Therefore, the benefit/risk has not yet been established in this population. Paediatric population The safety and efficacy of Tecartus in children and adolescents aged less than 18 years have not yet been established. No data are available.
Method of administration Tecartus is for intravenous use only. Tecartus must not be irradiated. Do NOT use a leukodepleting filter. Before administration, it must be confirmed that the patient’s identity matches the unique patient information on the Tecartus infusion bag and cassette.
5 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.
• For autologous use only, verify the patient ID to match the patient identifiers on the Tecartus infusion bag. • Once tubing has been primed, infuse the entire content of the Tecartus infusion bag within 30 minutes by either gravity or a peristaltic pump.
For detailed instructions on preparation, administration, accidental exposure and disposal of Tecartus, see section […]
11 Table 1 Adverse drug reactions identified with Tecartus System Organ Class (SOC) Frequency Adverse reactions Infections and infestations Very common Unspecified pathogen infections Bacterial infections Fungal infections Viral Infections Blood and lymphatic system disorders Very common Leukopeniaa Neutropeniaa Lymphopeniaa Thrombocytopeniaa Anaemiaa Febrile neutropenia Common Coagulopathy Immune system disorders Very common Cytokine Release Syndromeb Hypogammaglobulinaemia Common Hypersensitivity Haemophagocytic lymphohistiocytosis Metabolism and nutrition disorders Very common Hypophosphataemiaa Decreased appetite Hypomagnesaemia Hyperglycaemiaa Common Hypoalbuminemiaa Dehydration Psychiatric disorders Very common Delirium Anxiety Insomnia Nervous system disorders Very common Encephalopathy Tremor Headache Immune effector cell-associated neurotoxicity syndrome (ICANSb, c) Aphasia Dizziness Neuropathy Common Seizures, including status epilepticus Ataxia Increased intracranial pressure Eye Disorders Common Visual impairment Cardiac disorders Very common Tachycardias Bradycardias Common Non-ventricular arrhythmias Vascular disorders Very common Hypotension Hypertension Haemorrhage Common Thrombosis Respiratory, thoracic and mediastinal disorders Very common Cough Dyspnoea Pleural effusion 12 System Organ Class (SOC) Frequency Adverse reactions Hypoxia Common Respiratory failure Pulmonary oedema Gastrointestinal disorders Very common Nausea Diarrhoea Constipation Abdominal pain Vomiting Oral pain Common Dry mouth Dysphagia Skin and subcutaneous tissue disorders Very common Rash Skin disorder Musculoskeletal and connective tissue disorders Very common Musculoskeletal pain Motor dysfunction Renal and urinary disorders Very common Renal insufficiency Common Urine output decreased General disorders and administration site conditions Very common Oedema Fatigue Pyrexia Pain Chills Common Infusion related reaction Investigations Very common Alanine aminotransferase increaseda Blood uric acid increaseda Aspartate aminotransferase increaseda Hypocalcaemiaa Hyponatraemiaa Direct bilirubin increaseda Hypokalaemiaa Common Bilirubin increaseda Only cytopenias that resulted in (i) new or worsening clinical sequelae or (ii) that required therapy or (iii) adjustment in current therapy are included in Table 1.
a Frequency based on Grade 3 or higher laboratory parameter. b See section Description of selected adverse reactions. c The frequency of ICANS has been estimated from events reported in the post-marketing setting. ZUMA-2 data cutoff: 24 July 2021; ZUMA-3 data cutoff: 23 July 2021 Description of selected adverse reactions from ZUMA-2 and ZUMA-3 (n=182), and from post marketing reporting Cytokine release syndrome CRS occurred in 91% of patients.
Twenty percent (20%) of patients experienced Grade 3 or higher (severe or life-threatening) CRS. The median time to onset was 3 days (range: 1 to 13 days) and the median duration was 9 days (range: 1 to 63 days). Ninety-seven percent (97%) of patients recovered from CRS.
The most common signs or symptoms associated with CRS among the patients who experienced CRS included pyrexia (94%), hypotension (64%), hypoxia (32%), chills (31%), tachycardia (27%), sinus tachycardia (23%), headache (22%), fatigue (16%), and nausea (13%).
Serious adverse reactions that may be associated with CRS included hypotension (22%), pyrexia (15%), hypoxia (9%), tachycardia (3%), dyspnoea (2%) and sinus tachycardia (2%). 4 for monitoring and management guidance. 13 Neurologic events and adverse reactions Neurologic adverse reactions occurred in 69% […]
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.
Monitoring of vital signs and organ functions must be considered depending on the severity of the reaction. 2). Blood, organ, tissue and cell donation Patients treated with Tecartus must not donate blood, organs, tissues, or cells for transplantation.
Active central nervous system (CNS) lymphoma There is no experience of use of this medicinal product in patients with active CNS lymphoma defined as brain metastases confirmed by imaging. In ALL, asymptomatic patients with a maximum of CNS-2 disease (defined as white blood cells <5/μL in cerebral spinal fluid with presence of lymphoblasts) without clinically evident neurological changes were treated with Tecartus, however, data is limited in this population.
Therefore, the benefit/risk of Tecartus has not been established in these populations. Concomitant disease Patients with a history of or active CNS disorder or inadequate renal, hepatic, pulmonary, or cardiac function were excluded from the studies.
These patients are likely to be more vulnerable to the consequences of the adverse reactions described below and require special attention. Cytokine release syndrome Nearly all patients experienced some degree of CRS. Severe CRS, which can be fatal, was observed with Tecartus with a median time to onset of 3 days (range: 1 to 13 days).
8). Diagnosis of CRS requires excluding alternate causes of systemic inflammatory response, including infection. Management of cytokine release syndrome associated with Tecartus 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 Tecartus 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 Medicines Agency shortage catalogue, the treatment centre /clinical facility must have access to suitable alternative measures instead of tocilizumab to treat CRS.
7 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.
, 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 is to be considered.
In some cases, macrophage activation syndrome (MAS) and haemophagocytic lymphohistiocytosis (HLH) may occur in the setting of CRS. Evaluation for haemophagocytic […]