Breyanzi · 4.8 Undesirable effects · 1

HOS-287345 · has-adverse-reaction-information · PDF-Seite 13

Summary of the safety profile LBCL Patients who received one prior line of therapy for LBCL The adverse reactions described in this section were characterised in 177 patients infused with Breyanzi from 3 pooled studies TRANSFORM [BCM-003], PILOT [017006], and TRANSCEND WORLD [JCAR017-BCM-001, Cohort 2]. The most common adverse reactions of any grade were neutropenia (71%), anaemia (45%), CRS (45%) and thrombocytopenia (43%). The most common serious adverse reactions were CRS (12%), neutropenia (3%), bacterial infectious disorders (3%), infection with an unspecified pathogen (3%), thrombocytopenia (2%), 13 febrile neutropenia (2%), pyrexia (2%), aphasia (2%), headache (2%), confusional state (2%), pulmonary embolism (2%), anaemia (1%), upper gastrointestinal haemorrhage (1%) and tremor (1%). The most common Grade 3 or higher adverse reactions included neutropenia (68%), thrombocytopenia (33%), anaemia (31%), lymphopenia (17%), leukopenia (17%), febrile neutropenia (5%) and bacterial infections (5%). Patients who received two or more prior lines of therapy for LBCL The adverse reactions described in this section were characterised in 384 patients infused with Breyanzi from 4 pooled studies (TRANSCEND [017001], TRANSCEND WORLD [JCAR017-BCM-001, Cohort 1, 3 and 7], PLATFORM [JCAR017-BCM-002] and OUTREACH [017007]. The most common adverse reactions of any grade were neutropenia (68%), anaemia (45%), CRS (38%), fatigue (37%) and thrombocytopenia (36%). The most common serious adverse reactions were CRS (18%), infection with an unspecified pathogen (6%), pyrexia (4%), encephalopathy (4%), febrile neutropenia (4%), neutropenia (3%), thrombocytopenia (3%), aphasia (3%), bacterial infectious disorders (3%), tremor (3%), confusional state (3%), anaemia (2%) and hypotension (2%). The most common Grade 3 or higher adverse reactions included neutropenia (64%), anaemia (34%), thrombocytopenia (29%), leukopenia (25%), lymphopenia (9%), infection with an unspecified pathogen (8%) and febrile neutropenia (8%). FL The adverse reactions described in this section were characterised in 130 patients infused with Breyanzi from study TRANSCEND-FL (FOL-001). The most common adverse reactions of any grade were neutropenia (68%), CRS (58%), anaemia (40%), headache (29%), thrombocytopenia (29%) and constipation (21%). The most common serious adverse reactions were CRS (9%), aphasia (4%), febrile neutropenia (3%), pyrexi

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HOS-287341 · has-contraindication-information · PDF-Seite 5

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

HOS-287340 · has-indication-information · PDF-Seite 3

Breyanzi is indicated for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL) and follicular lymphoma grade 3B (FL3B), who relapsed within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy. Breyanzi is indicated for the treatment of adult patients with relapsed or refractory DLBCL, PMBCL and FL3B, after two or more lines of systemic therapy. Breyanzi is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. Breyanzi is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy including a Bruton’s tyrosine kinase (BTK) inhibitor.

HOS-287343 · has-interaction-information · PDF-Seite 12

No interaction studies have been performed in humans. Monoclonal antibodies directed against the epidermal growth factor receptor (anti-EGFR mabs) Long-term persistence of CAR T-cells may be affected by the subsequent use of anti-EGFR mabs however, there is limited information available on the clinical use of anti-EGFR mabs in patients treated with Breyanzi. Live vaccines The safety of immunisation with live viral vaccines during or following treatment with Breyanzi 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 Breyanzi treatment, and until immune recovery following treatment.

HOS-287344 · has-pregnancy-information · PDF-Seite 12

Women of childbearing potential/Contraception in males and females Pregnancy status for women of child-bearing potential should be verified using a pregnancy test prior to starting treatment with Breyanzi. 12 See the prescribing information for fludarabine and cyclophosphamide 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 Breyanzi. Pregnancy There are no data from the use of lisocabtagene maraleucel in pregnant women. No animal reproductive and developmental toxicity studies have been conducted to assess whether it can cause foetal harm when administered to a pregnant woman (see section 5.3). It is not known if lisocabtagene maraleucel 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, Breyanzi is not recommended for women who are pregnant, or for women of childbearing potential not using contraception. Pregnant women should be advised on the potential risks to the foetus. Pregnancy after Breyanzi therapy should be discussed with the treating physician. Assessment of immunoglobulin levels and B-cells in newborns of mothers treated with should be considered. Breast-feeding It is unknown whether lisocabtagene maraleucel is excreted in human milk or transferred to the breast- feeding child. Women who are breast-feeding should be advised of the potential risk to the breast-fed child. Fertility There are no data on the effect of lisocabtagene maraleucel on fertility.

HOS-287342 · 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 after expiry date of the product. Autologous use Breyanzi is intended solely for autologous use and must not, under any circumstances, be administered to other patients. Breyanzi must not be administered if the information on the product labels and release for infusion certificate (RfIC) do not match the patient’s identity. Reasons to delay treatment Due to the risks associated with Breyanzi treatment, infusion should be delayed if a patient has any of the following conditions: • Unresolved serious adverse events (especially pulmonary events, cardiac events, or hypotension), including those after preceding chemotherapies. • Active uncontrolled infections, or inflammatory disorders. • Active graft-versus-host disease (GVHD). 5 In case of delayed Breyanzi infusion, see section 4.2. Blood, organ, tissue and cell donation Patients treated with Breyanzi must not donate blood, organs, tissues and cells for transplantation. Central nervous system (CNS) lymphoma There is no experience of use of Breyanzi in patients with primary CNS lymphoma. There is limited clinical experience of use of Breyanzi for secondary CNS lymphoma (see section 5.1). Prior treatment with an anti-CD19 therapy There is limited clinical experience with Breyanzi in patients exposed to prior CD19-directed therapy (see section 5.1). There are limited clinical data available on CD19-negative patients treated with Breyanzi. Patients with CD19-negative status by immunohistochemistry may still express CD19. The potential risks and benefits associated with treatment of CD19-negative patients with Breyanzi should be considered. Cytokine release syndrome CRS including fatal or life-threatening reactions can occur following Breyanzi infusion. For patients who received one prior line of therapy for large B-cell lymphoma (LBCL), the median time to onset was 4 days (range: 1 to 63 days, with the upper limit due to CRS onset, without fever, reported in one patient). For patients who received two or more prior lines of therapy for LBCL, the median time to onset was 4 days (range: 1 to 14 days). For patients who received Breyanzi for FL, the median time to onset was 6 days (range:

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