4.1. Therapeutic indications

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 26 years of age and above with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL).

4.2. Posology and method of administration

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 MHRA Central Alerting System, suitable alternative measures to treat CRS instead of tocilizumab must be available prior to infusion.

Posology

Tecartus is intended for autologous use only (see section 4.4).

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 x 106–2 x 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. The availability of the treatment must be confirmed prior to starting the lymphodepleting regimen (i.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. The availability of the treatment must be confirmed prior to starting the lymphodepleting regimen (i.e. date of product availability for shipment).

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. 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.

Mantle cell lymphoma and acute lymphoblastic leukaemia

Pre-medication

• To minimise potential acute infusion reactions, it is recommended that patients be pre‑medicated with paracetamol 500 to 1,000 mg given orally and diphenhydramine 12.5 to 25 mg intravenously or orally (or equivalent medicinal products) approximately 1 hour before the infusion of Tecartus.

• Prophylactic use of systemic corticosteroids is not recommended (see section 4.5).

Monitoring prior to infusion

• In some patient groups at risk, a delay of the Tecartus infusion may be indicated (see section 4.4 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.

• Patients must remain within proximity of a qualified treatment centre for at least 4 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.

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 MHRA Central Alerting System, 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 6.6.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Contraindications of the lymphodepleting chemotherapy must be considered.

4.4. Special warnings and precautions for use

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. If the infusion is delayed for more than 2 weeks after the patient has received the lymphodepleting chemotherapy, lymphodepleting chemotherapy regimen must be administered again (see section 4.2)

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.

Patients must remain within proximity of a qualified treatment centre for at least 4 weeks following infusion and seek immediate medical attention should signs or symptoms of CRS or neurological adverse reactions occur. Monitoring of vital signs and organ functions must be considered depending on the severity of the reaction.

Serological testing

Screening for HBV, HCV, and HIV must be performed before collection of cells for manufacturing of Tecartus (see section 4.2).

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). Patients must be closely monitored for signs or symptoms of these events, such as high fever, hypotension, hypoxia, chills, tachycardia and headache (see section 4.8

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. In the exceptional case where tocilizumab is not available due to a shortage that is listed in the MHRA Central Alerting System, the treatment centre 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.

CRS has been known to be associated with end organ dysfunction (e.g., 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 lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) is to be considered in patients with severe or unresponsive CRS. HLH/MAS should be managed per local institutional and/or national or European/international clinical guidelines.

Tecartus continues to expand and persist following administration of tocilizumab and corticosteroids. Tumour necrosis factor (TNF) antagonists are not recommended for management of Tecartus‑associated CRS.

Neurologic adverse reactions

Severe neurologic adverse reactions, also known as immune effector cell-associated neurotoxicity syndrome (ICANS), have been observed in patients treated with Tecartus, which could be life-threatening or fatal. The median time to onset was 7 days (range: 1 to 262 days) following Tecartus infusion (see section 4.8).

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.

Infections and febrile neutropenia

Severe infections, which could be life‑threatening, were very commonly observed with Tecartus (see section 4.8).

Patients must be monitored for signs and symptoms of infection before, during and after infusion and treated appropriately. Prophylactic antibiotics must be administered according to standard institutional guidelines.

Febrile neutropenia has been observed in patients after Tecartus infusion (see section 4.8) 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, life‑threatening and fatal opportunistic infections including disseminated fungal infections and viral reactivation (e.g., HHV‑6 and progressive multifocal leukoencephalopathy) have been reported. The possibility of these infections should be considered in patients with neurologic events and appropriate diagnostic evaluations must be performed.

Viral reactivation

Viral reactivation, e.g. Hepatitis B virus (HBV) reactivation, can occur in patients treated with medicinal products directed against B cells and could result in fulminant hepatitis, hepatic failure, and death.

Prolonged cytopenias

Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Tecartus infusion and must be managed according to standard guidelines. Grade 3 or higher prolonged cytopenias following Tecartus infusion occurred very commonly and included thrombocytopenia, neutropenia, and anaemia (see section 4.8). Patient blood counts must be monitored after Tecartus infusion.

Hypogammaglobulinaemia

B‑cell aplasia leading to hypogammaglobulinaemia can occur in patients receiving treatment with Tecartus. Hypogammaglobulinaemia was very commonly observed in patients treated with Tecartus (see section 4.8). Hypogammaglobulinaemia predisposes patients to have infections. Immunoglobulin levels should be monitored after treatment with Tecartus and managed using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement in case of recurrent infections and must be taken according to standard guidelines.

Hypersensitivity reactions

Serious hypersensitivity reactions including anaphylaxis, may occur due to DMSO or residual gentamicin in Tecartus.

Secondary malignancies including of T cell and myeloid origin

Patients treated with Tecartus may develop secondary malignancies. T-cell malignancies have been reported following treatment of haematological malignancies with a BCMA- or CD19-directed CAR T-cell therapy. T-cell malignancies, including CAR-positive malignancies, have been reported within weeks and up to several years following administration of a CD19- or BCMA-directed CAR T-cell therapy. There have been fatal outcomes. In the event that a secondary malignancy occurs, contact the company to obtain instructions on patient samples to collect for testing.

Myelodysplastic syndrome and acute myeloid leukaemia, including cases with fatal outcomes, have occurred in patients following treatment with Tecartus.

Patients must be monitored life-long for secondary malignancies.

Tumour lysis syndrome (TLS)

TLS, which may be severe, has occasionally been observed. To minimise risk of TLS, patients with elevated uric acid or high tumour burden should receive allopurinol, or an alternative prophylaxis, prior to Tecartus infusion. Signs and symptoms of TLS must be monitored, and events managed according to standard guidelines.

Prior stem cell transplantation (GvHD)

It is not recommended that patients who underwent an allogeneic stem cell transplant and suffer from active acute or chronic GvHD receive treatment because of the potential risk of Tecartus worsening GvHD.

Prior treatment with anti‑CD19 therapy

Tecartus is not recommended if the patient has relapsed with CD19‑negative disease after prior anti‑CD19 therapy.

CD19-negative acute lymphoblastic leukaemia disease

Tecartus is not recommended for patients who have CD19-negative disease or an unconfirmed CD19 status.

Sodium content

This medicinal product contains 300 mg sodium per infusion, equivalent to 15% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Long-term follow up

Patients are expected to enrol in a registry in order to better understand the long‑term safety and efficacy of Tecartus.

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed with Tecartus.

Prophylactic use of systemic corticosteroids may interfere with the activity of Tecartus. Prophylactic use of systemic corticosteroids is therefore not recommended before infusion (see section 4.2).

Administration of corticosteroids as per the toxicity management guidelines does not impact the expansion and persistence of CAR T cells.

Live vaccines

The safety of immunisation with live viral vaccines during or following Tecartus treatment has not been studied. As a precautionary measure, vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Tecartus treatment, and until immune recovery following treatment.

4.6. Fertility, pregnancy and lactation

Women of childbearing potential/Contraception in males and females

The pregnancy status of women of childbearing potential must be verified before starting Tecartus treatment.

See the prescribing information for lymphodepleting chemotherapy for information on the need for effective contraception in patients who receive the lymphodepleting chemotherapy.

There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with Tecartus.

Pregnancy

There are no available data with Tecartus use in pregnant women. No reproductive and developmental toxicity animal studies have been conducted with Tecartus to assess whether it can cause foetal harm when administered to a pregnant woman (see section 5.3).

It is not known if Tecartus has the potential to be transferred to the foetus. Based on the mechanism of action, if the transduced cells cross the placenta, they may cause foetal toxicity, including B‑cell lymphocytopenia. Therefore, Tecartus is not recommended for women who are pregnant, or for women of childbearing potential not using contraception. Pregnant women must be advised on the potential risks to the foetus. Pregnancy after Tecartus therapy must be discussed with the treating physician.

Assessment of immunoglobulin levels and B‑cells in newborn infants of mothers treated with Tecartus must be considered.

Breast-feeding

It is unknown whether Tecartus is excreted in human milk or transferred to the breast‑feeding child. Breast‑feeding women must be advised of the potential risk to the breast‑fed child.

Fertility

No clinical data on the effect of Tecartus on fertility are available. Effects on male and female fertility have not been evaluated in animal studies.

4.7. Effects on ability to drive and use machines

Tecartus has major influence on the ability to drive and use machines.

Due to the potential for neurologic events, including altered mental status or seizures, patients must not drive or operate heavy or potentially dangerous machines until at least 8 weeks after infusion or until resolution of neurologic adverse reactions.

4.8. Undesirable effects

Summary of the safety profile

Mantle cell lymphoma

The safety data described in this section reflect exposure to Tecartus in ZUMA‑2, a Phase 2 study in which a total of 82 patients with relapsed/refractory MCL received a single dose of CAR‑positive viable T cells (2 × 106 or 0.5 × 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 CRS (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%).

Acute lymphoblastic leukaemia

The safety data described in this section reflect exposure to Tecartus in ZUMA‑3, a Phase 1/2 study in which a total of 100 patients with relapsed/refractory B-cell precursor ALL received a single dose of CAR-positive viable T cells (0.5 × 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.

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

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

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

Eye Disorders

Common

Visual impairment

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. See section 4.4 for monitoring and management guidance.

Neurologic events and adverse reactions

Neurologic adverse reactions occurred in 69% of patients. Thirty‑two percent (32%) of patients experienced Grade 3 or higher (severe or life‑threatening) adverse reactions. The median time to onset was 7 days (range: 1 to 262 days). Neurologic events resolved for 113 out of 125 patients (90.4%) with a median duration of 12 days (range: 1 to 708 days). Three patients had ongoing neurologic events at the time of death, including one patient with the reported event of serious encephalopathy and another patient with the reported event of serious confusional state. The remaining unresolved neurologic events were Grade 2. Ninety-three percent of all treated patients experienced the first CRS or neurological event within the first 7 days after Tecartus infusion.

The most common neurologic adverse reactions including ICANS represented tremor (32%), confusional state (27%), encephalopathy (27%), aphasia (21%), and agitation (11%). Serious adverse reactions including encephalopathy (15%), aphasia (6%), confusional state (5%) and serious cases of cerebral oedema which may become fatal have occurred in patients treated with Tecartus. See section 4.4 for monitoring and management guidance.

Febrile neutropenia and infections

Febrile neutropenia was observed in 12% of patients after Tecartus infusion. Infections occurred in 87% of the 182 patients treated with Tecartus in ZUMA‑2 and ZUMA-3. Grade 3 or higher (severe, life‑threatening or fatal) infections occurred in 30% of patients including unspecified pathogen, bacterial, fungal and viral infections in 23%, 8%, 2% and 4% of patients respectively. See section 4.4 for monitoring and management guidance.

Prolonged cytopenias

Cytopenias are very common following prior lymphodepleting chemotherapy and Tecartus therapy.

Prolonged (present on or beyond Day 30 or with an onset at Day 30 or beyond) Grade 3 or higher cytopenias occurred in 48% of patients and included neutropenia (34%), thrombocytopenia (27%) and anaemia (15%). See section 4.4 for management guidance.

Hypogammaglobulinaemia

Hypogammaglobulinaemia occurred in 12% of patients. Grade 3 or higher hypogammaglobulinemia occurred in 1% of patients. See section 4.4 for management guidance.

Immunogenicity

The immunogenicity of Tecartus has been evaluated using an enzyme‑linked immunosorbent assay (ELISA) for the detection of binding antibodies against FMC63, the originating antibody of the anti‑CD19 CAR. To date, no anti‑CD19 CAR T‑cell antibody immunogenicity has been observed in MCL patients. Based on an initial screening assay, 17 patients in ZUMA-2 at any time point tested positive for antibodies; however, a confirmatory orthogonal cell‑based assay demonstrated that all 17 patients in ZUMA-2 were antibody negative at all time points tested. Based on an initial screening assay, 16 patients in ZUMA-3 tested positive for antibodies at any timepoint. Among patients with evaluable samples for confirmatory testing, two patients were confirmed to be antibody-positive after treatment. One of the 2 patients had a confirmed positive antibody result at Month 6. The second patient had a confirmed positive antibody result at retreatment Day 28 and Month 3. There is no evidence that the kinetics of initial expansion, CAR T‑cell function and persistence of Tecartus, or the safety or effectiveness of Tecartus, were altered in these patients.

Secondary malignancies

There have been cases of the following adverse effect(s) reported after treatment with other CAR T-cell products, which might also occur after treatment with Tecartus: secondary malignancy of T-cell origin.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

There are no data regarding the signs of overdose with Tecartus.