S312: is brexucabtagene autoleucel a cost-effective treatment for refractory/relapsed acute lymphoblastic leukemia? a pharmacoeconomic analysis in the perspective of the public healthcare system.

Topic: 36. Ethics and health economics Background: Acute Lymphoblastic Leukemia (ALL) is a rare aggressive neoplasm incurring in about 2/100,000 adults per year, but less than half of them are projected to survive 5 years after diagnosis. Expected overall survival (OS) is particularly poor (i.e. less than 12 months) in patients relapsing or not responding after/to frontline therapy (R/R) despite being offered standard of care (SOC) with Blinatumomab, Inotuzumab Ozogamicin, tyrosin kinase inhibitors and/or chemotherapy, possibly followed by allogeneic stem cell-transplantation (aSCT). Brexucabtagene autoleucel (BA) is a chimeric antigen receptor (CAR) T-cell therapy that allowed 56% of R/R LLA patients to achieve a durable complete response and a median OS of 25.4 months. Aims: The present study aimed at comparing the clinical and economic outcomes of R/R LLA patients aged >25 years treated with BA versus SOC in the Italian Healthcare System. Methods: We developed a partitioned-survival model to extrapolate event-free, overall survival and healthcare costs of R/R LLA patients and intended to receive BA or SOC. The source of safety and survival data for BA was the mITT cohort of ZUMA-3 trial, while other trial data (e.g. INO-VATE, PACE and TOWER) were used for SOC. Long-term OS and EFS were estimated using mixture cure modelling methods: log-logistic and log-normal parametrization of OS and EFS curves was usually employed, respectively. Moreover, consolidation aSCT was modelled in 23.48% of patients achieving a response to SOC and in 18% of the patients treated with BA, based on trial data. Patients whose disease had not progressed after 2 years were assumed to experience long-term remission. Patients’ quality of life (i.e. utilities) were driven from ZUMA-3 trial and the published literature. Resource consumption was based on trial data and published literature. Unit costs were estimated from an Italian National Healthcare System perspective and based on national charges, ex-factory drug costs and published economic analyses. Costs and health outcomes were discounted at 3% per year. Sensitivity analyses were performed to test model robustness. Results: Median estimated survival for BA was 9.68 life years (LY), while it was 2.78-4.98 LYs for SOC. Discounted and quality-adjusted life expectancy was 4.98 quality-adjusted years (QALY) for BA versus 1.34-3.04 for SOC (Table). Cumulative discounted costs in the 50-year time horizon were €390,269 for patients intended-to-receive BA, versus €118,618-278,293 for SOC, which corresponded to a cost of €46,415-76,384 per QALY gained. At a willingness-to-pay threshold of 100,000/QALY probabilistic sensitivity analysis demonstrated that BA had a probability higher than 85% of being cost-effective versus SOC. The most influential model parameters were patients’ quality of life, BA acquisition cost, and the proportion of patients receiving HSCT. The results were also sensitive to the time horizon of the analysis. Summary/Conclusion: Brexucabtagene autoleucel is a potentially cost-effective alternative to SOC for with R/R LLA, allowing to spare aSCT in >5% of patients and should therefore be incorporated into the optimal treatment sequence for such patients. Table. Incremental cost-effectiveness of brexucabtagene autoleucel (BA) versus standard of care (SOC), namely Inotuzumab (INO), Ponatinib (PONA), Chemoimmunotherapy (CIT), or Blinatumomab (BLINA).Keywords: Cost effectiveness, CAR-T, Acute lymphoblastic leukemia, Clinical outcome