The GoCART Coalition: Guidance for pharmacists

Guidance on the provision of CAR T and cellular therapy services in hospital pharmacy has been published by the GoCART Coalition to harmonise implementation across Europe. Here, Tiene Bauters PharmD PhD, Pharmacy, Department of Pediatric Hemato-Oncology & Stem Cell Transplantation at Ghent University Hospital in Belgium, shares an overview of the involvement of the pharmacist in CAR T-cell services. 

Cancer is one of the leading causes of death globally, and improving therapeutic strategies in haematology and oncology remains a priority in healthcare. In the last decade, immunotherapies that treat cancers using the patient’s immune system to recognise, attack and kill malignant cells have reached the market.

A significant breakthrough in this field has been the advent of chimeric antigen receptor (CAR) T-cell therapy. In CAR T-cell therapy, which is classified as an advanced therapy medicinal product, autologous T-cells are genetically engineered ex vivo to express CARs that direct the patient’s lymphocytes to kill the tumour cells. The engineered cells are expanded in a dedicated production facility and then administered via infusion to the patient.^1,2

CAR T-cell products, such as tisagenlecleucel and axicabtagene ciloleucel, have been available on the European market for clinical use since 2018^3-5 and are used to treat patients who have not responded to other first-line therapies.

CAR T-cells have achieved unprecedented success in haematological cancers, especially in relapsed/refractory B-cell malignancies in adults and children, and are currently licensed for lymphoma, leukaemia and myeloma.^5,6 However, the associated side effects, such as cytokine release syndrome and neurologic toxicities, can be extremely serious and potentially life-threatening.² Clinical research is ongoing to expand the therapeutic window to target solid tumours using CAR T-cell platforms.^6,7

As CAR T-cells are biological drugs, they are more complex than conventional medicines, resulting in many challenges around implementation in clinical practice. Challenges include complex supply chains, the management of severe side effects, the accreditation for facilities performing CAR T-cell therapy, regulatory requirements and reimbursement, and appropriate education of qualified staff.⁸

The GoCART Coalition

In 2020, the European Society of Blood and Marrow Transplantation and the European Hematology Association joined forces and launched GoCART – a multi-stakeholder coalition in the field of gene and cellular therapies manufactured from cells and tissues of haematopoietic origin.

GoCART aims to promote patient access to novel cellular therapies, bringing together different stakeholders, including healthcare professionals, health authorities, pharmaceutical companies, patient representatives, health technology assessment bodies, reimbursement agencies and medical non-profit organisations.^8,9

Of the many stakeholders involved in CAR T therapy, pharmacists are crucial.¹⁰ Once the CAR T-cells are manufactured, they are delivered to hospital pharmacies, making pharmacists central in ensuring appropriate governance and management.^11,12

In addition, due to the complexity of these therapies, pharmacists must ensure adequate training during their implementation, management and monitoring of toxicities and adverse events, and effective collaboration with all members of the multidisciplinary team.¹¹

Many documents and checklists detail every stage of the pathway in preparing CAR T. One example is the ‘Institutional Readiness for Marketed CAR T therapy: Guidance for Chief Pharmacists’, edited by Anne Black.¹⁰ This outlines key areas in which (chief) pharmacists should focus their pharmaceutical expertise prior to an organisation implementing CAR T therapy.

The document presents a helpful flow diagram outlining a stepwise approach to CAR T covering: governance; approval of the order; apheresis and manufacture; product receipt and storage; issue and transportation to the clinical area; preparation, administration and monitoring; pharmacy aseptic services; and practical aspects of medicines management. Checklists and a standard operating procedure for the various steps are also included.¹⁰

Similarly, representatives of the Sociedad Espanola de Farmacia Hospitalaria (Spanish Society of Hospital Pharmacy) have developed a CAR T Medicines Management Procedure, and the Society’s oncology group has published a document detailing hospital pharmacists’ roles and responsibilities with CAR T medicines.^13,14

GoCART Coalition guidance

In August 2023, an expert group of European hospital pharmacists in the GoCART Coalition published ‘Implementation and operational management of marketed CAR T-cell therapies, a guidance by the GoCART Coalition Pharmacist Working Group’.¹²

The document aims to harmonise the implementation of hospital pharmacy CAR T services. It provides practical guidance and supports the implementation and safe operational use of marketed CAR T-cell products within hospital pharmacies, primarily throughout Europe. It also outlines the key areas that pharmaceutical expertise should focus on and the key considerations for the hospital pharmacy. The guidance is divided into two sections.

• Considerations for implementation

Section 1 outlines considerations for hospital pharmacists in implementing CAR T-cell services. The different roles and steps to be undertaken by hospital pharmacists are clearly described. Topics including regulation and governance, agreements with manufacturers, collaborative agreements with cell storage facilities and training, and competence requirements are described.

• Operational considerations

Section 2 highlights operational considerations in the patient and product pathway. It covers:

• Patient eligibility and approval of treatment
• Leukapheresis
• Manufacturing bridging therapy (managed in line with hospital standards and pharmacy processes for chemotherapy)
• Product receipt and storage (even when pharmacists are not directly involved, they must oversee the process)
• Clinical verification of lymphodepleting conditioning regimens and CAR T-cell prescription
• Post-infusion monitoring and pharmacovigilance.

Interestingly, the different stages of the process where direct pharmacist clinical intervention is required are detailed, as well as the processes that they are only required to oversee or where no involvement is needed.

Conclusion

Pharmacists are essential in the provision of CAR T and cellular therapies. The GoCART Coalition Pharmacist Working Group’s mission is to develop standards of care to advance the field of cellular therapies in Europe, and their recent publication provides practical education and recommendations on the implementation and safe use of marketed CAR T-cell products within hospital pharmacies that can be adapted to local requirements.

References

1. Feins S et al. An introduction to chimeric antigen receptor (CAR) T-cell immunotherapy for human cancer. Am J Hematol 2019;94:S3–S9.
2. Larson R. Treatment of relapsed or refractory acute lymphoblastic leukemia in adults. In: UpToDate, Lowenberg, Rosmarin, UpToDate, Waltham, MA, 2023.
3. Kymriah. Summary of Product Characteristics.
4. Yescarta. Summary of Product Characteristics.
5. Maude SL et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med 2018;378(5):439–48.
6. Khan AN et al. CAR-T cell therapy in hematological malignancies: Where are we now and where are we heading for? Eur J Haematol 2023; Aug 7.
7. Watanabe K et al. Expanding the Therapeutic Window for CAR T Cell Therapy in Solid Tumors: The Knowns and Unknowns of CAR T Cell Biology. Front Immunol 2018;9:2486.
8. Terwel SR et al. GoCART. In: Kröger N et al (eds). The EBMT/EHA CAR-T Cell Handbook [Internet]. Cham (CH): Springer; 2022: Chapter 43.
9. GoCART Coalition.
10. Black A. Pharmacy institutional readiness for marketed CAR-T therapy: guidance for chief pharmacists V4 (updated January 2020) 2018.
11. Galassi M, Moreno-Martínez ME. Role of Pharmacists. In: Kröger N et al (eds) The EBMT/EHA CAR-T Cell Handbook [Internet]. Cham (CH): Springer; 2022: Chapter 41.
12. Nezvalova-Henriksen K et al. Implementation and operational management of marketed chimeric antigen receptor T cell (CAR-T Cell) therapy – a guidance by the GoCART Coalition Pharmacist Working Group. Bone Marrow Transpl 2023; Aug 1.
13. Moreno-Martínez ME et al. Hospital pharmacists’ roles and responsibilities with CAR-T medicines. Farm Hosp 2020;44(1):26–31.
14. Sociedad Española de Farmacia Hospitalaria. Procedimiento de gestión de medicamentoss CAR-T. 2019.