Abstract
Introduction: The advancement of cell therapies, such as chimerized CAR-T cells, represents a fundamental advance for the treatment of several types of hematological conditions, as demonstrated by the great efficacy observed in clinical studies. However, the high cost of cell therapies represents a challenge for their incorporation into health systems and their economic sustainability. In 2022, three cell therapies were approved by the National Health Surveillance Agency for the treatment of conditions such as lymphomas and leukemia in Brazil. The objective of this work was to identify and characterize cost-effectiveness assessments of CAR-T therapies for their incorporation into the health system in different countries. Methods: The cost-effectiveness assessments for the incorporation of CAR-T therapies were obtained from documents from the agencies of Australia (MSAC), Canada (CADTH), France (HAS), Scotland (SMC), and the United Kingdom (NICE). Information on the type of CAR-T therapy, disease and target population, comparator, incremental cost-effectiveness ratio (ICER), and the final recommendation of the regulatory agency were collected. The searches were conducted until July/2023. Results: 29 evaluations for the incorporation of five CAR-T therapies were identified: axicabtagene ciloleucel (MSAC, CADTH, HAS, SMC, NICE), brexucabtagene autoleucel (MSAC, HAS, CADTH, SMC, NICE), ciltacabtagene autoleucel (MSAC), idecabtagene vicleucel (CADTH), and tisagenlecleucel (MSAC, CA-DTH, HAS, SMC, NICE). These therapies were evaluated for 8 types of lymphomas or leukemias, with diffuse large B-cell lymphoma (14 evaluations) and acute lymphoblastic leukemia (7 evaluations) being the most frequent conditions. The main comparators adopted for the cost-effectiveness assessment were usual care, consisting of salvage chemotherapy options and allogeneic hematopoietic stem cell transplantation. However, comparators such as tyrosine kinase inhibitors, clofarabine, lenalidomide and immunobiological technologies were also used. Twenty-three (79%) of the evaluations received a favorable opinion for incorporation. Overall, the ICER result showed wide variation between agencies. In Canada, CADTH indicated the ICER of CAR-T therapies ranging from CAD 53,269/QALY to CAD 679,053/QALY. The French agency HAS indicated an ICER value between EUR 111,649/QALY and EUR 295,406/QALY for the evaluated CAR-T cell therapies. The SMC reported a range of GBP 44,151/QALY and GBP 49,711/QALY for the cost-effectiveness outcome for CAR-T therapies. Given the uncertainty of the long-term benefit of CAR-T therapies, the analysis conducted by NICE indicated that the most plausible ICER ranges from below GBP 30,000/QALY to above GBP 50,000/QALY, but some analyses indicated a range for the ICER of GBP 46,898/QALY and GBP 72,920/QALY (brexucabtagene autoleucel) and GBP 42,991/QALY and GBP 55,403/QALY (tisagenlecleucel). The MSAC agency indicated confidentiality in the ICER result. Discussion and conclusions: This study highlighted that CAR-T cell therapies have been gaining prominence internationally, with their incorporation being evaluated by different countries. These therapies are associated with a high ICER, however, there was a favorable decision for incorporation in 79% of the analyses. The implementation of CAR-T therapies presents challenges such as their high cost, making it necessary to discuss forms of financing for the incorporation of these technologies into the Brazilian health system.
