OBJECTIVES: Provide an overview of CAR-T cells clinical trials under development, analyze the methodology of HTA (health technology assessments) currently published, and identify challenges related to CAR-T cells compared to existing treatments that may impact the CEA (cost-effectiveness analysis).

METHODS: A search of phase 2 and 3 CAR-T cells clinical trials under development was performed on ClinicalTrials™ database. Results were crossed check with findings from other databases. Secondly, a targeted literature review was conducted to identify publicly available information from HTA appraisals related to curative and innovative therapies. As a final step, a comparison of methodologies and issues raised in these HTA appraisals were analyzed.

RESULTS: A total of 182 clinical trials were identified, including 90% phase 2 studies. Two CAR-T cells therapies have recently been approved by the FDA and two CEAs report have been published. In both studies, a payer perspective and a life time horizon were chosen, but different modelling structures and assumptions related to data extrapolation were used. Despite a significant health gain and an ICER (incremental cost-effectiveness ratio) which fell below the range normally considered cost-effective, HTA bodies raised concern around uncertainty surrounding survival data extrapolation, mainly due to the lack of long-term data and the phase 2 study design. In addition, given the specific cycle of administration for CAR-T cells, a lack of experience of using the treatment, the absence of a regulatory framework, valorization of costs and extrapolation of clinical data remain uncertain.

CONCLUSIONS: Many CAR-T cells clinical trials are currently ongoing in different therapeutic areas. Among available CAR-T cell CEAs, the same challenges seem to be encountered. Majority of trials are single arms, with a small sample size and a limited follow-up limiting comparability of data and adding a large uncertainty around data extrapolation. Valorization of resources is also difficult given the limited experience of use.