Abecma

HOS-287243 · has-adverse-reaction-information · PDF-Seite 13

Summary of the safety profile The safety data described in this section reflect the exposure to Abecma in the KarMMa, CRB-401 and KarMMa-3 studies in which 409 patients with relapsed and refractory multiple myeloma received Abecma. In KarMMa (N = 128) and CRB-401 (N = 56), the median duration of follow-up (from 13 Abecma infusion to data cutoff date) was 20.8 months. In KarMMa-3 (N = 225), the median duration of follow-up was 29.3 months. The most common adverse reactions (≥ 20%) included CRS (84.6%), neutropenia (80.0%), anaemia (63.6%), thrombocytopenia (55.0%), infections - pathogen unspecified (43.8%), hypophosphataemia (33.3%), diarrhoea (33.0%), leukopenia (32.8%), hypokalaemia (32.0%), fatigue (29.8%), nausea (28.1%), lymphopenia (26.9%), pyrexia (24.7%), infections - viral (23.2%), headache (22.5%), hypocalcaemia (22.0%), hypomagnesaemia (21.3%), and arthralgia (20.0%); other common adverse events occurring at lower frequency and considered clinically important included hypotension (18.6%), upper respiratory tract infection (15.6%), hypogammaglobulinemia (13.7%), febrile neutropenia (11.2%), pneumonia (11.0%), tremor (5.6%), somnolence (5.6%), encephalopathy (3.4%), syncope (3.2%), and aphasia (2.9%). Serious adverse reactions occurred in 57.2% of patients. The most common serious adverse reactions (≥ 5%) included CRS (10.3%), and pneumonia (7.1%); other serious adverse events occurring at lower frequency and considered clinically important include febrile neutropenia (4.2%), pyrexia (3.7%), neutropenia (2.7%), sepsis (2.7%), confusional state (2.4%), haemophagocytic lymphohistiocytosis (1.7%), thrombocytopenia (1.5%), encephalopathy (1.5%), dyspnoea (1.5%), seizure (1.0%), mental status changes (1.0%), hypoxia (0.7%) and disseminated intravascular coagulation (0.5%). The most common Grade 3 or 4 adverse reactions (≥ 5%) were neutropenia (77.3%), anaemia (50.9%), thrombocytopenia (42.5%), leukopenia (31.5%), lymphopenia (25.9%), hypophosphataemia (19.8%), infections - pathogen unspecified (15.2%), febrile neutropenia (10.5%), infections - viral (7.6%), pneumonia (6.8%), hypertension (6.6%), hypocalcaemia (5.6%) and infections - bacterial (5.4%). Grade 3 or 4 adverse reactions were more often observed within the initial 8 weeks post-infusion (93.2%) compared to after 8 weeks post-infusion (58.1%). The most frequently reported Grade 3 or 4 adverse reactions reported within the first 8 weeks a

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HOS-287239 · has-contraindication-information · PDF-Seite 4

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-287238 · has-indication-information · PDF-Seite 2

Abecma is indicated for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. 2

HOS-287241 · has-interaction-information · PDF-Seite 12

No interaction studies have been performed. The co-administration of agents known to inhibit T cell function has not been formally studied. The co-administration of agents known to stimulate T cell function has not been investigated and the effects are unknown. Tocilizumab or siltuximab and corticosteroid use Some patients required tocilizumab or siltuximab and/or corticosteroid for the management of CRS (see section 4.8). The use of tocilizumab or siltuximab and/or corticosteroids for CRS management was more common in patients with higher cellular expansion. In the KarMMa-3 study, patients with CRS treated with tocilizumab or siltuximab had higher Abecma cellular expansion levels, as measured by 3.1-fold and 2.9-fold higher median Cmax (N = 156) and AUC0-28 days (N = 155), respectively, compared to patients who did not receive tocilizumab or siltuximab (N = 64 for Cmax and N = 63 for AUC0-28 days). Patients with CRS treated with corticosteroids had higher Abecma cellular expansion levels, as measured by 2.3-fold and 2.4-fold higher median Cmax (N = 60) and AUC0-28 days (N = 60), respectively, compared to patients who did not receive corticosteroids (N = 160 for Cmax and N = 158 for AUC0-28 days). Similarly, in the KarMMa study, patients with CRS treated with tocilizumab had higher Abecma cellular expansion levels, as measured by 1.4-fold and 1.6-fold higher median Cmax (N = 66) and AUC0-28 days (N = 65), respectively, compared to patients who did not receive tocilizumab (N = 61 for Cmax and N = 60 for AUC0-28 days). Patients with CRS treated with corticosteroids had higher Abecma cellular expansion levels, as measured by 1.7-fold and 2.2-fold higher median Cmax (N = 18) and AUC0-28 days (N = 18), respectively, compared to patients who did not receive corticosteroids (N = 109 for Cmax and N = 107 for AUC0-28 days). Live vaccines The safety of immunisation with live viral vaccines during or following treatment with Abecma 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 Abecma treatment and until immune recovery following treatment. 12

HOS-287242 · has-pregnancy-information · PDF-Seite 13

Women of childbearing potential/Contraception in males and females Pregnancy status for women of childbearing potential should be verified using a pregnancy test prior to starting treatment with Abecma. 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 Abecma. Pregnancy There are no data from the use of idecabtagene vicleucel in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with idecabtagene vicleucel to assess whether it can cause foetal harm when administered to a pregnant woman (see section 5.3). It is not known if idecabtagene vicleucel 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 plasma cell aplasia or hypogammaglobulinaemia. Therefore, Abecma 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 Abecma therapy should be discussed with the treating physician. Assessment of immunoglobulin levels in newborn infants of mothers treated with Abecma should be considered. Breast-feeding It is unknown whether idecabtagene vicleucel cells are excreted in human milk or transferred to the breast-feeding child. A risk to the breast-fed infant cannot be excluded. 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 idecabtagene vicleucel on fertility. Effects of idecabtagene vicleucel on male and female fertility have not been evaluated in animal studies.

HOS-287240 · 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 product. Autologous use Abecma is intended solely for autologous use and must not, under any circumstances, be administered to other patients. Abecma must not be administered if the information on the product labels and the release for infusion certificate (RfIC) do not match the patient’s identity. 4 Rapidly progressing disease Before selecting patients for Abecma treatment, physicians should consider the impact of high-risk cytogenetic abnormalities, Revised International Staging System (R-ISS) stage III, presence of extramedullary plasmacytoma or high tumour burden, particularly for patients who have rapidly progressing disease that may affect their ability to receive CAR T infusion in due time. For these patients, optimising bridging therapy may be particularly important. Some patients may not benefit from Abecma treatment due to potential increased risk of early death (see section 5.1). Reasons to delay treatment Due to the risks associated with Abecma treatment, infusion should be delayed up to 7 days 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 infections or inflammatory disorders (including pneumonitis, myocarditis or hepatitis). • Active graft-versus-host disease (GVHD). Concomitant disease Patients with active central nervous system (CNS) disorder or inadequate renal, hepatic, pulmonary or cardiac function are likely to be more vulnerable to the consequences of the adverse reactions described below and require special attention. Central nervous system pathology There is no experience of use of Abecma in patients with CNS involvement of myeloma or other pre- existing, clinically relevant CNS pathologies. Prior allogeneic stem cell transplantation It is not recommended that patients receive Abecma within 4 months after an allogeneic stem cell transplant (SCT) because of the potential risk of Abecma worsening GVHD. Leukapheresis for Abecma manufacturing should be performed at least 12 weeks after allogeneic SCT. Prior treatment with an anti-BCM

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