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AUCATZYL is a brand name for Obecabtagene Autoleucel. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Aucatzyl is indicated for the treatment of adult patients (≥ 18 years) with relapsed or refractory B cell precursor acute lymphoblastic leukaemia (see section 5.1).
Verbatim from this product's MHRA label. Tap a section to expand.
Aucatzyl 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 Aucatzyl. Refer to the UK Public Assessment Report on the Medicines and Healthcare products Regulatory Agency (MHRA) website for details of leukapheresis, lymphodepletion and bridging therapies used in the clinical trials for Aucatzyl.
4). The target dose of Aucatzyl is 410 × 106 CD19 CAR-positive viable T cells supplied in three or more infusion bags. 6). Bone marrow assessment A bone marrow assessment must be available from a biopsy and/or aspirate sample obtained within 7 days prior to the commencement of the lymphodepleting chemotherapy.
The bone marrow assessment is used to determine the Aucatzyl dosage regimen. The treatment regimen consists of a split dose to be administered on Day 1 and Day 10 (± 2 days). Low Tumour Burden Regimen (where lymphoblasts make up ≤ 20% of all nucleated cells in a bone marrow biopsy obtained within 7 days prior to lymphodepletion): • Day 1: 100 × 106 cells administered via bag infusion • Day 10 (± 2 days): 10 × 106 cells administered via syringe and 300 × 106 cells administered via bag infusion High Tumour Burden Regimen (where lymphoblasts make up > 20% of all nucleated cells in a bone marrow biopsy obtained within 7 days prior to lymphodepletion): • Day 1: 10 × 106 cells administered via syringe • Day 10 (± 2 days): 100 × 106 cells administered via bag infusion and 300 × 106 cells administered via bag infusion If bone marrow assessment results are inconclusive: • Repeat the biopsy or aspirate, and note that a repeat biopsy or aspirate must only be taken prior to lymphodepleting chemotherapy.
e. administration of the 10 × 106 dose on Day 1) per the Aucatzyl Dose Schedule Planner. Pretreatment conditioning (lymphodepleting chemotherapy) Confirm availability of Aucatzyl prior to starting lymphodepleting chemotherapy. Refer to the UK Public Assessment Report on the MHRA website for details of the lymphodepletion therapy used in the FELIX clinical trial for Aucatzyl.
Premedication • To minimise the risk of an infusion reaction, premedicate with paracetamol (1,000 mg orally) approximately 30 minutes prior to Aucatzyl infusion. • Avoid prophylactic use of systemic corticosteroids because this may interfere with the activity of Aucatzyl.
Summary of the safety profile The safety of Aucatzyl was evaluated in one open-label, single-arm study (study FELIX) in which 127 adult patients with relapsed or refractory B cell acute lymphoblastic leukaemia received a median dose of 410 × 106 viable CAR T cells (range: 10 to 480 × 106 viable CAR T cells).
Exposure to Aucatzyl was preceded by unstimulated leukapheresis followed by lymphodepletion with fludarabine and cyclophosphamide (safety profiles for these procedures were generally consistent with those expected with leukapheresis and lymphodepletion).
Bridging therapy was permitted. 4) months. The most common adverse reaction of any grade included cytokine release syndrome (69%), infections-pathogen unspecified (45%) and musculoskeletal pain (31%). The most common non-laboratory Grade 3 or higher adverse reactions were infections-pathogen unspecified (32%), febrile neutropenia (24%) and bacterial infectious disorders (11%).
The most common serious adverse reactions of any grade included infections- pathogen unspecified (28%), febrile neutropenia (13%) and immune effector cell- associated neurotoxicity syndrome (9%). Patients undergo leukapheresis, bridging therapy and lymphodepletion therapy prior to administration of Aucatzyl.
Refer to local / national guidance documents for information on adverse events that may occur in association with the leukapheresis procedure. Refer to the relevant summaries of product characteristics for information on adverse events that may arise subsequent to exposure to medicinal products used in the bridging and lymphodepletion therapies.
Tabulated list of adverse reactions Table 1 summarises the adverse reactions in a total of 127 patients exposed to Aucatzyl in the Phase Ib and Phase II FELIX study. These reactions are presented by MedDRA system organ class and by frequency.
Refer to the UK Public Assessment Report on the MHRA website for details of leukapheresis, lymphodepletion and bridging therapies used in the FELIX clinical trial for Aucatzyl. 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 the expiry date of the product. Autologous use Aucatzyl is intended solely for autologous use and must not, under any circumstances, be administered to other patients.
Aucatzyl must not be administered if the information on the product labels and Release for Infusion Certificate do not match the patient’s identity. Monitoring • Patients must be monitored daily for 14 days after the first infusion for signs and symptoms of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and other toxicities.
• Frequency of monitoring after the first 14 days may be carried out at the physician’s discretion and continued for at least 4 weeks after the first infusion. • Patients must be instructed to remain within proximity of the qualified treatment centre for at least 4 weeks following the first infusion.
Reasons to delay treatment Delay Aucatzyl treatment if there are unresolved serious adverse reactions from preceding chemotherapies, if the patient is experiencing severe intercurrent infection, or has active graft-versus-host disease.
If the patient requires supplementary oxygen, Aucatzyl should only be infused, if considered appropriate, based on the treating physician’s benefit / risk assessment. Reasons to delay the second split dose Dosage delays or discontinuation may be required after the first split dose to manage adverse reactions.
Patients with Grade 2 cytokine release syndrome and / or Grade 1 immune effector cell- associated neurotoxicity syndrome following the first split dose may receive the second dose on Day 10 (± 2 days) up to Day 21 only if cytokine release syndrome has resolved to Grade 1 or less and immune effector cell-associated neurotoxicity syndrome has completely resolved.
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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Special populations Elderly No dose adjustment is required in patients over 65 years of age. Twenty percent of patients treated with Aucatzyl in the safety set (25/127) were 65 years of age and over. 2. Renal and hepatic impairment There is no clinical experience in patients with renal or hepatic impairment.
Patients with a history of renal or hepatic impairment are likely to be more vulnerable to the consequences of the adverse reactions described below and require special attention, and consideration on a case-by-case basis. Paediatric population The safety and efficacy of Aucatzyl in children and adolescents below 18 years of age have not yet been established.
Method of administration Aucatzyl is for autologous and intravenous use only. 6. Strictly follow Administration Instructions to minimise dosing errors.
Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 1:
Adverse drug reactions identified with Aucatzyl System Organ Class (SOC) Frequency Adverse reaction Infections and infestations Very Common Infections – pathogen unspecified Bacterial infectious disorders COVID-19 Viral infectious disorders excluding COVID-19 Fungal infectious disorders Blood and lymphatic system disorders Very Common Neutropeniaa Leukopeniaa Lymphopeniaa Thrombocytopenia a Anaemiaa Febrile neutropenia Coagulopathy Immune system disorders Very Common Cytokine release syndrome Common Hypogammaglobulinaemia Haemophagocytic lymphohistiocytosis Metabolism and nutrition disorders Very Common Decreased appetite Psychiatric disorders Common Delirium Nervous system disorders Very Common Headache Immune effector cell-associated neurotoxicity syndrome Encephalopathy Dizziness Common Tremor Cardiac disorders Very Common Tachycardia Common Arrhythmia Cardiac Failure Palpitations Vascular disorders Very Common Hypotension Haemorrhage Respiratory, thoracic and mediastinal disorders Very Common Cough Gastrointestinal disorders Very Common Nausea Diarrhoea Vomiting Abdominal Pain Constipation Common Stomatitis Skin and subcutaneous tissue disorders Very Common Rash Musculoskeletal and connective tissue disorders Very Common Musculoskeletal pain General disorders and administration site conditions Very Common Pyrexia Pain Fatigue Oedema Common Chills Investigations Very Common Alanine aminotransferase increaseda Weight decreased Hyperferritinaemia Aspartate aminotransferase increaseda Injury, poisoning and procedural complications Common Infusion related reaction a Frequency based on Grade 3 or higher laboratory parameter.
Description of selected adverse reactions Cytokine release syndrome Cytokine release syndrome was reported in 69% (87/127) of patients, including Grade 3 cytokine release syndrome in 2% (3/127) of patients. There were no reported Grade 4 or 5 events.
The median time to onset of cytokine release syndrome of any grade was 8 days (range: 1 to 23 days) with a median duration 5 days (range: 1 to 21 days). The most common manifestations of cytokine release syndrome among patients who experienced cytokine release syndrome included fever (69%), hypotension (25%) and hypoxia (13%).
Sixty-four percent (56/87) of patients experienced cytokine release syndrome after the first, but prior to the second infusion of Aucatzyl. In the study, 80% (70/87) of patients who experienced cytokine release syndrome had a high tumour burden at the time of lymphodepleting treatment (≥ 5% lymphoblasts in the bone marrow), with 39% (34/87) of patients presenting with > 75% lymphoblast in their bone marrow.
The primary treatment for cytokine release syndrome was tocilizumab (76%; 66/87), with patients also receiving corticosteroids (23%; 20/87) and other anti cytokine therapies (14%; 12/87). Haemophagocytic Lymphohistiocytosis / Macrophage Activation Syndrome Haemophagocytic lymphohistiocytosis / macrophage activation syndrome, including severe and life threatening reactions may occur following treatment with Aucatzyl.
Haemophagocytic lymphohistiocytosis / macrophage activation syndrome was reported in 2% (2/127) of patients and included Grade 3 and Grade 4 events with a time of onset at Day 22 and Day 41, respectively. One patient experienced a concurrent immune effector cell-associated neurotoxicity syndrome event after Aucatzyl infusion.
Immune Effector Cell-Associated Neurotoxicity Syndrome Immune effector cell-associated neurotoxicity syndrome, which may be severe, life-threatening or fatal, occurred in 23% (29/127) of patients, including Grade ≥ 3 in 7% (9/127) of patients following treatment with Aucatzyl.
In clinical studies, 90% (26/29) of patients who experienced immune effector cell- associated neurotoxicity syndrome and all patients who experienced Grade ≥ 3 immune effector cell-associated […]
For patients with Grade ≥ 3 (i) severe infection at the time of infusion of Aucatzyl or (ii) requirement for supplementary oxygen or (iii) other clinically relevant adverse reactions following the first split dose: consider postponing Aucatzyl up to Day 21 to allow the situation to resolve.
In addition, the second split dose is not to be administered if ≥ Grade 3 cytokine release syndrome, ≥ Grade 2 immune effector cell-associated neurotoxicity syndrome and / or ≥ Grade 3 pulmonary or cardiac toxicities are observed following the first split dose.
0. Cytokine release syndrome Refer to local institutional / national guidelines for advice on monitoring and management of cytokine release syndrome. Evaluation for haemophagocytic lymphohistiocytosis / macrophage activation syndrome is to be considered in patients with severe or unresponsive cytokine release syndrome.
Treatment should be administered per institutional standards. Availability of tocilizumab Treatment centres must have 24-hour immediate access to tocilizumab and emergency equipment must be available prior to infusion. In the exceptional case where tocilizumab is not available owing to a shortage, then alternatives to tocilizumab to treat cytokine release syndrome must be available prior to infusion.
Shortages of tocilizumab may be checked for in the MHRA Central Alerting System. Immune Effector Cell-associated Neurotoxicity Syndrome Patients should be monitored for signs and symptoms of immune effector cell- associated neurotoxicity syndrome.
Refer to local institutional / national guidelines for advice on monitoring and management of immune effector cell-associated neurotoxicity syndrome. Prolonged Cytopenias Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Aucatzyl infusion and should be managed according to institutional guidelines.
Patient blood counts must be monitored after Aucatzyl infusion. Severe infections Aucatzyl should not be administered to patients with clinically significant active systemic infections. 8). 8) and may be concurrent with cytokine release syndrome.
Patients with human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infection There is no clinical experience in patients with a positive test for HIV, active HBV, or active HCV infection. Screening for HBV, HCV, HIV and other infectious agents must be performed in accordance with clinical guidelines before collection of cells for manufacturing.
Leukapheresis material from patients with active HIV, active HBV, or active HCV infection will not be accepted for manufacturing. , HBV reactivation, can occur in patients treated with medicinal products directed against B cells and could result in fulminant hepatitis, hepatic failure, and death.
Hypogammaglobulinaemia Hypogammaglobulinaemia is caused by B cell aplasia and has been seen as a consequence of depletion of normal B cells by CAR T cell therapy. 8). Hypogammaglobulinaemia predisposes patients to become more susceptible to infections.
Immunoglobulin levels should be monitored after treatment with Aucatzyl and managed per institutional guidelines including infection precautions, antibiotics or antiviral prophylaxis and immunoglobulin replacement. Prior stem cell transplantation (graft versus host disease) It is recommended that patients do not receive Aucatzyl within 3 […]