Objectives: Adult patients with relapsed/refractory acute lymphoblastic leukemia have poor prognosis and limited treatment alternatives. Brexucabtagene autoleucel (BREXU-CEL) is the only approved CAR-T with promising outcomes in adults (≥26years). We aimed to estimate its cost-effectiveness versus blinatumomab (BLIN), inotuzumab ozogamicin (INO), and salvage chemotherapy (CHEMO) for patients ≥26 years in Greece.

Methods: A three-state partitioned-survival model was used to estimate treatment-specific health outcomes and costs over a lifetime time horizon. Patients entered the model in the pre-progression health state and could transition to progression or death. Clinical data were derived from ZUMA-3 for BREXU-CEL (median follow-up 37.3 months), TOWER for BLIN, and INO-VATE for INO and CHEMO. Matching-adjusted indirect comparisons provided efficacy data for BREXU-CEL adjusted for differences between the study populations. Standard parametric and mixture cure models were used. National data on general population mortality were applied. Utilities for the EFS and PD health state were derived from ZUMA-3. Direct medical costs of pre-treatment, drug acquisition costs (ex-factory prices), treatment administration, monitoring, allogeneic stem-cell transplant, adverse event and end-of-life costs were derived from up-to-date national sources and published literature (€, 2023). Annual discount rate of 3.5% was applied on costs and health outcomes.

Results: Compared with BLIN, INO, and CHEMO, BREXU-CEL resulted in 2.68, 3.94, and 5.32 life-years gained, and 2.25, 3.02, and 4.06 quality-adjusted life-years (QALYs) gained per patient, respectively. The incremental costs of BREXU-CEL versus BLIN, INO, and CHEMO were €131,688, €111,706, and €248,781, respectively. BREXU-CEL’s incremental cost-effectiveness ratios were €58,442/QALY versus BLIN, €36,971/QALY versus INO, and €61,248/QALY versus CHEMO. Scenario analysis showed consistent results.

Conclusions: Considering the high unmet need in this patient population due to limited survival outcomes of existing therapeutic alternatives, BREXU-CEL provides a valuable and potentially cost-effective alternative to current treatments, deriving its value from incremental survival and health-related quality of life benefits.