OBJECTIVES : Today’s healthcare system strives for more personalised treatments to improve patient outcomes. CAR-T cell therapy is a novel immunotherapy in which a patient’s own T cells are genetically modified to express chimeric antigen receptor (CAR), which can attach to the surface of cancer cells and destroy them. We reviewed the appraisal of this therapy in the UK.

METHODS : National Institute for Health and Care Excellence (NICE) and Scottish Medicine Consortium (SMC) health technology appraisals for CAR-T cell therapies were reviewed.

RESULTS : To date, two CAR-T cell therapies have been appraised by NICE and SMC, tisagenlecleucel and axicabtagene ciloleucel. The appraisal of tisagenlecleucel in relapsed/refractory B-cell acute lymphoblastic leukaemia in people aged ≤25 years faced a number of challenges, including high uncertainty of the data on overall survival, subsequent stem cell transplant rates and immunoglobulin usage, lack of comparator data, and high cost-effectiveness estimates. To mitigate these, tisagenlecleucel has been conditionally approved by both NICE and SMC through the Cancer Drug Fund (CDF) and Patient Access Scheme, respectively. Due to data uncertainties and high cost-effectiveness estimates, both NICE and SMC rejected the use of tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Additional negotiations lead NICE to use a managed access agreement (MAA) which allows the use of tisagenlecleucel in DLBCL under CDF while additional evidence is being collected. Axicabtagene ciloleucel was also approved by NICE for treating DLBCL and primary mediastinal large B-cell lymphoma after ≥2 systemic therapies through the use of a MAA, but not by the SMC.

CONCLUSIONS : Despite their potential benefits to patients, CAR-T cell therapies face a number of challenges during HTA appraisal in the UK, including uncertainties in clinical effectiveness and in long-term costs and benefits. Risk sharing between the NHS and manufacturers and the use of innovative payment methodologies should be further investigated.