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TECARTUS is a brand name for Brexucabtagene Autoleucel, supplied as a suspension. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: TECARTUS (brexucabtagene autoleucel suspension for intravenous infusion) 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) after two or more lines of systemic therapy including a Bruton’s…
Verbatim from this product's HC label. Tap a section to expand.
TECARTUS should be administered by experienced health professionals at specialized treatment centres (see WARNINGS AND PRECAUTIONS). 1 Dosing Considerations • For intravenous (IV) use only • Single infusion product • For autologous use only; do NOT infuse TECARTUS if the information on the patient-specific label on the infusion bag does not match the intended patient.
• Do not use a leukodepleting filter. • Do not irradiate TECARTUS. • Due to the risks associated with TECARTUS, consider delaying lymphodepleting chemotherapy and TECARTUS treatment if the patient has one or more of the following conditions: clinically significant cardiac dysfunction, pulmonary dysfunction, renal insufficiency, acute neurologic toxicity, active uncontrolled infection or inflammation, and active graft-versus-host disease (see CLINICAL TRIALS).
Serious Warnings and Precautions • Cytokine Release Syndrome (CRS), including fatal and life-threatening reactions, occurred in patients receiving TECARTUS. Do not administer TECARTUS if a patient has active uncontrolled infection or inflammatory disorders, active graft-versus-host disease (GVHD) or unresolved serious adverse reactions from prior therapies.
Monitor for CRS after treatment with TECARTUS. Provide supportive care, tocilizumab, or tocilizumab and corticosteroids, as needed (see WARNINGS AND PRECAUTIONS). • Neurologic adverse reactions, including fatal and life-threatening reactions, occurred in patients receiving TECARTUS, including concurrently with CRS or independently of CRS.
Monitor for neurologic adverse reactions after treatment with TECARTUS. Provide supportive care, tocilizumab (if with concurrent CRS), or corticosteroids, as needed (see WARNINGS AND PRECAUTIONS). • TECARTUS should be administered by experienced health professionals at specialized treatment centres (see WARNINGS AND PRECAUTIONS).
2 Recommended Dose and Dosage Adjustment Adults TECARTUS is provided as a single-dose, one-time treatment in a patient-specific infusion bag. Recommended Dosage for MCL Each single infusion bag of TECARTUS contains a suspension of anti-CD19 chimeric antigen receptor (CAR)-positive T cells in approximately 68 mL.
The target dose is 2 x 106 anti-CD19 CAR-positive viable T cells per kg body weight (range: 1 x 106 – 2 x 106 CAR-positive viable T cells/kg), with a maximum of 2 x 108 CAR-positive viable T cells for patients 100 kg and above. Recommended Dosage for ALL Each single infusion bag of TECARTUS contains a suspension of anti-CD19 CAR-positive viable T cells in approximately 68 mL.
2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. 5 × 106 anti-CD19 CAR T cells/kg) that was weight-based (see CLINICAL TRIALS). The most common non-hematological adverse reactions (in ≥ 20%) include: pyrexia (94%), CRS (91%), hypotension (57%), encephalopathy (51%), fatigue (50%), tachycardias (45%), other pathogen infections (43%), chills (41%), hypoxia (40%), cough (39%), tremor (38%), musculoskeletal pain (35%), edema (35%), headache (35%), nausea (35%), motor dysfunction (33%), constipation (29%), diarrhea (28%), decreased appetite (26%), dyspnea (26%), rash (22%), insomnia (21%), pleural effusion (21%), aphasia (20%), hypertension (20%), and renal insufficiency (20%).
Serious adverse reactions occurred in 65% of patients. The most common serious adverse reactions (≥ 2%) include: encephalopathy (26%), other pathogen infection (22%), pyrexia (20%), CRS (15%), hypoxia (9%), aphasia (6%), renal insufficiency (6%), pleural effusion (5%), respiratory failure (5%), bacterial infections (4%), dyspnea (4%), fatigue (4%), non-ventricular arrhythmia (4%), viral infections (4%), diarrhea (2%), hypertension (2%), motor dysfunction (2%), seizure (2%), tachycardia (2%), and thrombosis (2%).
Grade 3 or higher adverse reactions were reported in 65% of patients. The most common Grade 3 or higher non-haematological adverse reactions included infections (32%) 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%).
Please see the SERIOUS WARNINGS AND PRECAUTIONS BOX at the beginning of Part I:
Health Professional Information. TECARTUS (brexucabtagene autoleucel) Page 9 of 44 General TECARTUS should be administered in a treatment facility with personnel trained in handling and administering TECARTUS and in the management of patients treated with TECARTUS, including monitoring and managing cytokine release syndrome and neurologic adverse reactions.
The facility should have immediate access to appropriate emergency equipment and intensive care unit. TECARTUS is intended solely for autologous use and should under no 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 label does not match the intended patient (see DOSAGE AND ADMINISTRATION). Patients with central nervous system (CNS) involvement were excluded from the pivotal ZUMA-2 (MCL) and ZUMA-3 (ALL) studies.
Therefore, the safety and efficacy of TECARTUS have not been established in these populations. Patients who had received a prior allogeneic stem cell transplant were excluded from the pivotal ZUMA-2 study due to the potential risk for TECARTUS to aggravate graft-versus-host disease (GvHD).
In ZUMA-3, 37% of ALL patients had received prior allogeneic stem cell transplant prior to TECARTUS infusion and GvHD was observed after TECARTUS infusion in 6% of patients (2/55 patients in Phase 2 and 3/23 patients in Phase 1). For other patient selection criteria, see CLINICAL TRIALS.
Patients treated with TECARTUS should not donate blood, organs, tissues and cells for transplantation. Secondary Malignancies Patients treated with TECARTUS may develop secondary hematological malignancies. T-cell malignancies have occurred following treatment with genetically modified autologous T-cell immunotherapies and may present as soon as weeks following infusion.
TECARTUS is contraindicated in patients who are hypersensitive to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
TECARTUS (brexucabtagene autoleucel) Page 5 of 44
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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The target dose is 1 × 106 anti-CD19 CAR-positive viable T cells per kg body weight, with a maximum of 1 × 108 CAR-positive viable T cells for patients 100 kg and above. Pediatrics (< 18 years of age) Health Canada has not authorized an indication for pediatric use.
Geriatrics (≥ 65 years of age) No dose adjustments are required for patients 65 years of age or older. 3 Reconstitution Not applicable. 4 Administration TECARTUS is for autologous use only. The patient’s identity must match the patient identifiers on the TECARTUS cassette and infusion bag.
Do NOT infuse TECARTUS if the information on the patient-specific label does not match the intended patient. Ensure that 4 doses of tocilizumab and access to emergency equipment are available prior to infusion and during the recovery period (see WARNINGS AND PRECAUTIONS).
Preparing Patient for TECARTUS Infusion Confirm availability of TECARTUS prior to starting the lymphodepleting chemotherapy regimen.
Pre-treatment (lymphodepleting chemotherapy) • MCL:
Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m2 intravenously and fludarabine 30 mg/m2 intravenously on the 5th, 4th, and 3rd day before infusion of TECARTUS.
TECARTUS (brexucabtagene autoleucel) Page 7 of 44 • ALL:
Administer a lymphodepleting chemotherapy regimen of fludarabine 25 mg/m2 intravenously over 30 minutes on the 4th, 3rd, and 2nd day and cyclophosphamide 900 mg/m2 intravenously over 60 minutes on the 2nd day before infusion of TECARTUS.
5 to 25 mg intravenously or 25 mg orally approximately 1 hour before TECARTUS infusion. • AVOID prophylactic use of systemic corticosteroids, as it may interfere with the activity of TECARTUS. Preparation of TECARTUS for Infusion • Coordinate the timing of TECARTUS thaw and infusion.
Confirm the infusion time in advance, and adjust the start time of TECARTUS thaw such that it will be available for infusion when the patient is ready. • Confirm patient identity: Prior to TECARTUS preparation, match the patient’s identity with the patient identifiers on the TECARTUS cassette.
• Do NOT remove the TECARTUS product bag from the cassette if the information on the patient- specific label does not match the intended patient. • Once patient identification is confirmed, remove the TECARTUS product bag from the cassette and check that the patient information on the cassette label matches the bag label.
• Inspect the infusion bag for any breaches of container integrity such as breaks or cracks before thawing. If the bag is compromised, follow the local guidelines (or call Kite Konnect at 1-833- 236-5483). • Place the infusion bag inside a second sterile bag or per local guidelines.
• Thaw the infusion bag at approximately 37°C using either a water bath or dry thaw method until there is no visible ice in the infusion bag. • Gently mix the contents of the bag to disperse clumps of cellular material. If visible cell clumps remain, continue to gently mix the contents of the bag.
Small clumps of cellular material should disperse with gentle manual mixing. Do NOT wash, spin down, and/or re-suspend TECARTUS in new media prior to infusion. Thawing should take approximately 3-5 minutes. • Once thawed, TECARTUS should be administered within 30 minutes but may be stored at room temperature […]
Grade 5 (fatal) adverse events were reported in 3 patients and included organizing pneumonia, staphylococcal bacteremia, and cardiac arrest. In ZUMA-2, 70% of patients received prophylactic allopurinol for TLS and 73% of patients received tocilizumab and/or corticosteroids for the treatment of adverse reactions (including CRS and neurologic adverse reactions), including 51% who required 2 or more doses of tocilizumab.
Table 4 summarizes the adverse reactions that occurred in at least 10% of patients treated with TECARTUS. 2 months. TECARTUS (brexucabtagene autoleucel) Page 19 of 44 Table 4 Summary of Adverse Reactions Observed in at Least 10% of Patients Treated with TECARTUS in ZUMA-2 Adverse Reaction Any Grade n (%) N = 82 Grade 3 or Higher n (%) N= 82 Blood and Lymphatic System Disorders Coagulopathy a 8 (10) 2 (2) Cardiac Disorders Tachycardias b 37 (45) 0 Bradycardias c 9 (11) 0 Non-ventricular arrhythmias d 8 (10) 3 (4) Gastrointestinal Disorders Nausea 29 (35) 1 (1) Constipation 24 (29) 0 Diarrhea 23 (28) 4 (5) Oral pain e 14 (17) 0 Abdominal pain f 13 (16) 0 Vomiting g 11 (13) 0 Dysphagia 8 (10) 2 (2) General Disorders and Administration Site Conditions Pyrexia 77 (94) 13 (16) Fatigue h 41 (50) 1 (1) Chills 34 (41) 0 Edema i 29 (35) 2 (2) Pain j 14 (17) 2 (2) Immune System Disorders Cytokine release syndrome 75 (91) 12 (15) Hypogammaglobulinemia k 13 (16) 1 (1) Infections and Infestations Other pathogen infections 35 (43) 21 (26) Viral infections 15 (18) 3 (4) Bacterial infections 11 (13) 5 (6) Fungal infections 8 (10) 0 Metabolism and Nutrition Disorders Decreased appetite 21 (26) 0 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain l 30 (37) 2 (2) Motor dysfunction m 27 (33) 5 (6) Nervous System Disorders Encephalopathy n 42 (51) 20 (24) Tremor 31 (38) 2 (2) Headache o 29 (35) 1 (1) Aphasia p 16 (20) 6 (7) Dizziness q 15 (18) 5 (6) Neuropathy r 11 (13) 2 (2) Psychiatric Disorders TECARTUS (brexucabtagene autoleucel) Page 20 of 44 Adverse Reaction Any Grade n (%) N = 82 Grade 3 or Higher n (%) N= 82 Insomnia 17 (21) 0 Delirium s 15 (18) 4 (5) Anxiety 14 (17) 0 Renal and Urinary Disorders Renal insufficiency t 16 (20) 6 (7) Urine output decreased u 9 (11) 1 (1) Respiratory, Thoracic and Mediastinal Disorders Hypoxia 33 (40) 16 (20) Cough v 32 (39) 0 Dyspnea w 21 (26) 5 (6) Pleural effusion 17 (21) 4 (5) Skin and Subcutaneous Tissue Disorders Rash x 18 (22) 3 (4) Vascular Disorders Hypotension y 47 (57) 23 (28) Hypertension 16 (20) 9 (11) Thrombosis z 14 (17) 3 (4) a.
Coagulopathy includes coagulopathy, disseminated intravascular coagulation, international normalised ratio increased. b. Tachycardias includes tachycardia, sinus tachycardia. c. Bradycardias includes bradycardia, sinus bradycardia. d. Non-ventricular arrhythmias includes atrial fibrillation, atrial flutter, cardiac flutter, palpitations, supraventricular tachycardia.
e. Oral pain includes oral pain, gingival pain, lip pain, oral mucosal erythema, oropharyngeal pain. f. Abdominal pain includes abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness. g. Vomiting includes vomiting, retching.
h. Fatigue includes fatigue, lethargy, malaise. i. Edema includes eyelid edema, face edema, generalised edema, localised edema, edema, edema peripheral, periorbital edema, peripheral […]
There have been fatal outcomes. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact the company for reporting and to obtain instructions on collection of patient samples for testing of secondary malignancies of T-cell origin.
Driving and Operating Machinery Due to the potential for neurologic events, including altered mental status or seizures, patients receiving TECARTUS are at risk for altered or decreased consciousness or coordination in the 8 weeks following TECARTUS 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. Endocrine and Metabolism Tumour lysis syndrome (TLS) TLS may occur in patients treated with TECARTUS.
To minimize the risk of TLS, patients with elevated uric acid or high tumour burden should receive prophylactic treatment (allopurinol, or an alternative prophylaxis) prior to TECARTUS infusion. TECARTUS (brexucabtagene autoleucel) Page 10 of 44 Immune Cytokine release syndrome (CRS) CRS, including fatal and life-threatening reactions, occurred following treatment with TECARTUS.
CRS occurred in 91% (75/82) of patients with MCL, including ≥ Grade 3 (Lee grading system) CRS in 15% of patients. Among the patients with MCL who died after receiving TECARTUS, one patient had a fatal CRS event. The median time to onset of CRS was 3 days (range: 1 to 13 days) and the median duration of CRS was 10 days (range: 1 to 50 days) for patients with MCL.
CRS occurred in 92% (72/78) of patients with ALL, including ≥ Grade 3 (Lee grading system) CRS in 26% of patients. The incidence of CRS (first occurrence) within the first seven days after TECARTUS infusion was 83% (68/82) in patients with MCL.
Three patients with ALL had ongoing CRS events at the time of death. 5 days (range: 1 to 12 days) and the median duration of CRS was 8 days (range: 2 to 63 days) for patients with ALL. The incidence of CRS (first occurrence) within the first seven days after TECARTUS infusion was 90% (70/78) in patients with ALL.
Among all MCL and ALL patients with CRS, key manifestations (>10%) included pyrexia (96%), hypotension (65%), tachycardia (50%), chills (33%), hypoxia (32%), headache (22%), fatigue (17%) and nausea (14%). Serious adverse reactions associated with CRS included hypotension, fever, hypoxia, dyspnea, and tachycardia (see ADVERSE REACTIONS).
Ensure that 4 doses of tocilizumab are available for each patient prior to TECARTUS infusion. Monitor patients daily for at least 7 days at the specialized healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion.
Counsel patients to remain within proximity of a specialized clinical facility for at least 4 weeks and to seek immediate medical attention, should signs or symptoms of CRS occur at any time (see Monitoring and Laboratory Tests, WARNINGS AND PRECAUTIONS).
An algorithm has been developed to guide the management of CRS in patients treated with TECARTUS (Table 2). At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.
Management of CRS Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, manage according to the recommendations in Table 2. Patients with Grade 1 CRS should be managed with vigilant supportive care and monitored for infection and fluid balance.
, 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 […]