OBJECTIVES: To understand how payers around the world have been appraising CAR T-cell therapies, identify evidence gaps in the assessments and how these were overcome in order to allow patient access, with the aim of informing future development of CAR T-cell therapies.

METHODS: We conducted an online, worldwide search for evidence of HTA appraisals of tisagenlecleucel and axicabtagene ciloleucel. We then reviewed the evidence, consisting mostly of HTA appraisals and press releases, looking for the outcome of each appraisal, the rationale behind the decision and whether any solutions were implemented to ensure patient access.

RESULTS: To date, we identified 24 HTA sources detailing individual appraisal outcomes of these drugs in acute lymphoblastic leukaemia (ALL) or diffuse large B-cell lymphoma (DLBCL), mostly from European countries. The most frequently mentioned evidence gaps were a comparator arm in the trials (14 sources), followed by longer-term data (11 sources), larger sample sizes and intention-to-treat reporting (5 sources each). Despite low level of evidence, the high unmet need in ALL led to perceived clinical benefit that was high (e.g. Denmark), moderate (e.g. France) or even unquantifiable (e.g. Germany), with reimbursement generally approved due to low budget impact. The cost-effectiveness of CAR T-cell therapy in DLBCL appears to be lower and the budget impact higher than in ALL, which has led to reimbursement denials (e.g. Netherlands, Scotland). Proposed solutions to allow sustainable patient access range from patient access schemes in the form of rebates (e.g. England, Scotland), coverage with evidence development (e.g. France, Germany, US) or performance-based arrangements (e.g. Spain, Israel, Japan, Australia).

CONCLUSIONS: Manufacturers could invest in longer, more robust trials with a comparator arm and RWE capture, engaging early-on with payers in order to discuss funding agreements and where data and financial trade-offs can be agreed, with the goal of enabling sustainable patient access.