Pharmacists Anne Black, David Caulfield and Sumantha Gabriel from Newcastle upon Tyne Hospitals have written an important new article for the Pharmaceutical Journal. It focuses on the process of implementing marketed Chimeric Antigen Receptor T-Cells (CAR-T) therapies (tisagenlecleucel and axicabtagene ciloleucel) in the UK. CAR-T cells are a type of Advanced Therapy Medicinal Product (ATMP) which is approved by the National Institute for Health and Care Excellence (NICE) to treat cancers (diffuse large B cell lymphoma and acute lymphoblastic leukaemia) in the UK.
An easy-to-follow diagram is used to illustrate how a CAR-T cell is produced. The complexity and number of steps in its manufacture demonstrates why these medicines cost in the region of £300,000 per single dose. However, clinical trial data spanning more than a decade is presented which exemplifies some of the positive responses witnessed in different patient groups across various clinical trials.
The extensive journey the patient and the cells undergo before the cells are ready for administration is described in a flow chart highlighting the various time points where the clinical pharmacist’s oversight is essential to ensure safe handling and administration. The flow diagram also emphasises how a multidisciplinary, collaborative approach is essential when delivering these medicines safely. To assist with this complex process Pharmacists from the Pan UK Pharmacy Working Group for ATMPs and the NHS Specialist Pharmacy Services have collaborated to produce checklists for each stage to ensure that the major points at each stage are covered by local systems.
Important clinical considerations are also described. This includes the various toxicities associated with CAR-T therapy, for example cytokine release syndrome (CRS) and neurotoxicity. The CRS associated side effects can be treated using defined protocols; however these can vary across clinical trials and institutions which is why it is essential for the clinical pharmacist to establish safe and practical guidance. Neurotoxicity management is illustrated with the ASTCT Immune-effector cell-associated encephalopathy tool. An example of the deterioration and improvement in handwriting in a patient with immune effector cell-associated neurotoxicity is presented in the article which demonstrates the drastic change in handwriting.
The responsibilities for pharmacists is summarised in a table to show how the implementation of CAR-T therapies has redefined the role of the chief pharmacist for ATMPs.
A link to the full article can be found here: https://www.pharmaceutical-journal.com/cpd-and-learning/cpd-article/implementing-chimeric-antigen-receptor-t-cell-therapy-in-practice/20207955.cpdarticle
