Detaljerad miljöinformation

Breyanzi® (lisocabtagene maraleucel) is an immunocellular therapy product composed of genetically modified autologous CD8+ and CD4+ T cells that express a CD19-specific chimeric antigen receptor (CAR). Lisocabtagene maraleucel is produced ex vivo using a third-generation, replication incompetent, self-inactivating, lentiviral viral vector (LVV) encoding an anti-CD19 CAR. Lisocabtagene maraleucel is intended 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. It is also used for the treatment of adult patients with relapsed or refractory DLBCL, PMBCL and FL3B, after two or more lines of systemic therapy.

Risk mitigation measures are employed to prevent release of lisocabtagene maraleucel into the environment. Breyanzi is administered in qualified controlled treatment centers.  Therapy is initiated under the strict direction and supervision of an experienced healthcare professional. All standard cleaning and sanitization procedures are applied, and access is restricted. A lisocabtagene maraleucel Product Administration Manual is provided and the appropriate medical personnel are trained in handling and administration of the drug product, and product accountability procedures.  Any partially used or unused lisocabtagene maraleucel, the absorbent barrier pads, any supplies used in the preparation and administration process, including the IV administration set, must be disposed of in accordance with the institution’s biohazard disposal policy and local regulatory requirements for the disposal of a genetically modified product.   No internal transport of product waste and potentially contaminated materials is foreseen other than from the site of administration to the institution’s facility for biohazard disposal. Materials will be transported in closed containers and according to the safety measures in place in accordance with the institution’s policy for disposal of potentially infectious patient material.  In case of accidental spill of product, surfaces must be disinfected to decontaminate surfaces and all contaminated material, including personal protective equipment.  No further product-specific measures are needed as the T-cells do not survive outside the human body.

Lisocabtagene maraleucel is not intended for direct release into the environment and it is not expected to be released into the environment.  T cells cannot survive outside of the human body and can neither propagate in exposed persons (except for the patient from whom the cells were derived), nor in the environment.  Therefore, a potential negative impact of lisocabtagene maraleucel on people or the environment is not expected. Any potential contact of the product with the healthcare providers during administration would be extremely limited and would not be expected to result in the expansion of the product in the exposed person.

T cells are a terminally differentiated cell type and are unable to proliferate or survive outside of the human body unless they are in highly controlled, tissue culture conditions (e.g., in the presence of specific cytokines in a defined cell culture medium with antigen-receptor stimulation).  These cells have stringent nutritional and metabolic requirements for survival, can be rapidly killed by physical inactivation/disinfectants, are therefore not viable in the environment.  The cells do not compete with other species in the natural environment. Patients treated with lisocabtagene maraleucel are informed not to donate blood, bone marrow, tissue, cells or organs in order to prevent transplantation of lisocabtagene maraleucel cells to immunodeficient patients.  CAR-positive T cells are devoid of any competitive advantage.  Since T cells do not survive outside of the body, horizontal gene transfer is unlikely if lisocabtagene maraleucel was released into the environment.  Additionally, lisocabtagene maraleucel is manufactured using a third-generation, replication incompetent, self-inactivating lentiviral vector, which carries minimal risk of horizontal and/or vertical lentivirus transmission, including to persons that handle or administer the gene therapy product, those involved in patient care, relatives, and others.  Each lot of LVV is tested for replication competent lentivirus (RCL) and the result must be negative prior to use in lisocabtagene maraleucel manufacturing. 

Based on these considerations, no negative consequences to the environment are expected.  Therefore, use of lisocabtagene maraleucel has been considered to result in insignificant environmental risk.

References

1. Environmental classification of pharmaceuticals at www.fass.se. Guidance for pharmaceutical companies, 2012

2. Breyanzi (lisocabtagene maraleucel) - Environmental risk assessment lisocabtagene maraleucel (Lisocabtagene maraleucel). Celgene, 2020

3. EPAR - Product Information for Breyanzi (lisocabtagene maraleucel). Available from: URL: https://www.ema.europa.eu/en/documents/product-information/breyanzi-epar-product-information_en.pdf Accessed 2 October 2024.