Etuvetidigene autotemcel

There are no data on the effects of etuvetidigene autotemcel on human fertility. Effects on male and female fertility have not been evaluated in animal studies. Data are available on the risk of infertility with myeloablative conditioning. It is therefore advised to consider fertility preservation options such as cryopreservation of semen or ova before treatment if possible.

Etuvetidigene autotemcel has not been studied in patients with evidence of myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome and acute myeloid leukemia, or other serious hematological disorders. Treatment with etuvetidigene autotemcel is not recommended in these patients.

There are no clinical data from the use of etuvetidigene autotemcel in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with etuvetidigene autotemcel.

A negative serum pregnancy test must be confirmed prior to the start of each mobilisation cycle and re-confirmed prior to myeloablative conditioning.

Women of childbearing potential and men capable of fathering a child must use effective method of contraception from start of mobilisation through at least 6 months after administration of myeloablative conditioning. Please also refer to the Summary of Product Characteristics for the mobilization, pre-treatment, and myeloablative conditioning medicinal products.

It is unknown whether etuvetidigene autotemcel is excreted in human milk or transferred to the breast-feeding child. There are no data available.

Breast-feeding should be discontinued during conditioning and etuvetidigene autotemcel administration because of the potential risks associated with conditioning.

The decision to breast-feed after etuvetidigene autotemcel treatment should be discussed with the treating physician, taking into account the benefit of breast-feeding for the child versus any potential adverse events from etuvetidigene autotemcel or from the underlying condition.

Fertility

There are no data on the effects of etuvetidigene autotemcel on human fertility. Effects on male and female fertility have not been evaluated in animal studies. Data are available on the risk of infertility with myeloablative conditioning. It is therefore advised to consider fertility preservation options such as cryopreservation of semen or ova before treatment if possible.

Etuvetidigene autotemcel has no influence on the ability to drive and use machines. The effect of the mobilisation agents and the conditioning agents on the ability to drive or use machines must be considered.

Summary of the safety profile

Treatment with etuvetidigene autotemcel is preceded by medical interventions, namely haematopoietic stem cell collection through peripheral blood mobilisation with G-CSF with plerixafor followed by apheresis, pre-treatment with rituximab (anti-CD20 monoclonal antibody) and reduced intensity conditioning, which carry their own risks. When assessing the safety of a treatment with etuvetidigene autotemcel, the safety profile and product information of the medicinal products used for peripheral blood mobilisation, pre-treatment and reduced intensity conditioning should be considered, in addition to the risks linked to the gene therapy

Adverse reactions were attributed to pre-treatment (including mobilisation/leukapheresis) conditioning regimen and administration site conditions (device related infection, catheter site haemorrhage very commonly reported).

Tabulated list of adverse reactions

The safety of etuvetidigene autotemcel was evaluated in 28 patients with WAS. The median duration of the follow up was 5.67 years (range: 0.37–13.26 years).

Given the small patient population, adverse reactions in the table below do not provide a complete perspective on the nature and frequency of these events.

Adverse reactions are listed by MedDRA body system organ class and by frequency. Frequencies are defined as: very common (≥1/10), and common (≥1/100 and <1/10).

Table 1. Adverse reactions attributed to mobilisation/apheresis and pre-treatment (G-CSF ± plerixafor, rituximab):

Table 2. Adverse reactions attributed to reduced intensity conditioning regimen (busulfan and fludarabine):

Administration site conditions very commonly reported were: device related infections and catheter site haemorrhage.