Tecartus · 4.8 Undesirable effects · 1

HOS-099161 · has-adverse-reaction-information · PDF-Seite 10

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 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%). 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. 10 Table 1 Adverse drug reactions identified with Tecartus S

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HOS-099157 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Contraindications of the lymphodepleting chemotherapy must be considered.

HOS-099156 · has-indication-information · PDF-Seite 3

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).

HOS-099159 · has-interaction-information · PDF-Seite 9

No interaction studies have been performed with Tecartus. Prophylactic use of systemic corticosteroids may interfere with the activity of Tecartus and is therefore not routinely recommended before infusion (see section 4.2). 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.

HOS-099160 · has-pregnancy-information · PDF-Seite 9

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. 9 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.

HOS-099158 · has-warning-information · PDF-Seite 5

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 5 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. If the post-infusion monitoring of patients takes p

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