Yescarta · 4.8 Undesirable effects · 1

HOS-098391 · has-adverse-reaction-information · PDF-Seite 10

Summary of the safety profile The safety data described in this section are from a total of 397 adult patients treated with Yescarta in three multi-centre pivotal clinical studies (ZUMA-1, ZUMA-5 and ZUMA-7) and post-marketing experience. Adverse reactions are adverse events from pivotal clinical studies and post-marketing experience medically assessed as reasonably attributed to axicabtagene ciloleucel. Relapsed or refractory DLBCL, PMBCL and DLBCL arising from follicular lymphoma after two or more lines of systemic therapy Safety data from ZUMA-1 reflects exposure to Yescarta in a Phase 1/2 study in which 108 patients received CAR-positive T cells based on a recommended dose which was weight-based. The data described are from the 54-month follow-up analysis where the median actual duration of follow-up was 23.5 months (range: 0.3 to 68.2 months). The most significant and frequently occurring adverse reactions were CRS (93%), encephalopathy (60%), and infections (40%). Serious adverse reactions occurred in 51% of patients. The most common (≥ 5%) serious adverse reactions included encephalopathy (22%), unspecified pathogen infections (15%), bacterial infection (6%), viral infection (6%), febrile neutropenia (5%), and fever (5%). The most common (≥ 5%) Grade 3 or higher non-haematological adverse reactions included encephalopathy (31%), unspecified pathogen infections (19%), CRS (11%), bacterial infection (9%), delirium (6%), hypertension (6%), hypotension (6%), transaminases increased (6%), and viral infection (6%). The most common Grade 3 or higher haematological adverse reactions included lymphopenia (99%), leukopenia (96%), neutropenia (94%), anaemia (65%), and thrombocytopenia (56%). DLBCL and HGBL that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy Safety data from ZUMA-7 reflects exposure to Yescarta in a Phase 3 study in which 170 patients received CAR-positive T cells based on a recommended dose which was weight-based. The data described are from an analysis where the median actual duration of follow-up was 23.2 months (range: 1.5 to 41.3 months). The most significant and frequently occurring adverse reactions were CRS (92%), encephalopathy (49%), and infections (45%). Serious adverse reactions occurred in 54% of patients. The most common (≥ 5%) serious adverse reactions included CRS (17%), encephalopathy (16%), unspecified pathogen infections (8%), fever (6%) and viral infection (5%). The

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HOS-098387 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to gentamicin (a possible trace residue). Contraindications of the lymphodepleting chemotherapy must be considered.

HOS-098386 · has-indication-information · PDF-Seite 2

Yescarta is indicated for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy. Yescarta is indicated for the treatment of adult patients with relapsed or refractory (r/r) DLBCL and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy. 2 Yescarta is indicated for the treatment of adult patients with r/r follicular lymphoma (FL) after three or more lines of systemic therapy.

HOS-098389 · has-interaction-information · PDF-Seite 8

No interaction studies have been performed with Yescarta. Prophylactic use of systemic corticosteroids may interfere with the activity of Yescarta and is therefore not routinely recommended before infusion (see section 4.2). 8 Live vaccines The safety of immunisation with live viral vaccines during or following treatment with Yescarta has not been studied. As a precautionary measure, vaccination with live vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta treatment, and until immune recovery following treatment.

HOS-098390 · has-pregnancy-information · PDF-Seite 9

Women of childbearing potential/Contraception in males and females The pregnancy status of women of child bearing potential must be verified before starting Yescarta 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 Yescarta. Pregnancy There are no available data with Yescarta use in pregnant women. No reproductive and developmental toxicity animal studies have been conducted with Yescarta to assess whether it can cause foetal harm when administered to a pregnant woman (see section 5.3). It is not known if Yescarta 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, Yescarta 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 Yescarta therapy must be discussed with the treating physician. Assessment of immunoglobulin levels and B-cells in newborns of mothers treated with Yescarta must be considered. Breast-feeding It is unknown whether Yescarta is excreted in human milk or transferred to the breast-feeding child. A risk to the breast-fed infant cannot be excluded. Breast-feeding women must be advised of the potential risk to the breast-fed child. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Yescarta therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. Fertility No clinical data on the effect of Yescarta on fertility are available. Effects on male and female fertility have not been evaluated in animal studies.

HOS-098388 · has-warning-information · PDF-Seite 4

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 expiry date of the medicinal product. 4 Autologous use Yescarta 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 Yescarta infusion bag and cassette. Yescarta must not be administered if the information on the patient-specific infusion bag and cassette label does not match the patient’s identity. General Warnings and precautions of lymphodepleting chemotherapy must be considered. Reasons to delay treatment Due to the risks associated with Yescarta 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. • 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 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

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