Background: FLT3-ITD mutations in acute myeloid leukemia (AML) confer a high risk of relapse following initial remission. While post–allogeneic hematopoietic cell transplantation (HCT) maintenance with FLT3 inhibitors is increasingly used in clinical practice, particularly in patients with measurable residual disease (MRD), the cost-effectiveness of this strategy remains uncertain. The BMT CTN 1506 (MORPHO) trial (Levis et al) evaluated gilteritinib maintenance versus placebo after HCT and showed improved relapse-free survival (RFS) among patients post-HCT MRD-positive FLT3-ITD AML, but no benefit in those without detectable MRD post-HCT. Given the high cost and potential toxicities of gilteritinib, we present a value-based assessment of gilteritinib maintenance in the MRD-positive FLT3-ITD AML post-HCT population.

Objective: To determine the cost-effectiveness of gilteritinib maintenance therapy versus placebo in patients with MRD-positive FLT3-ITD AML following HCT.

Methods: We developed a state-transition microsimulation model to estimate health and economic outcomes in a target population of adults with MRD-positive FLT3-ITD AML who are relapse-free after allogeneic HCT. The model simulated three post-HCT health states, which were: relapse-free survival, relapse, and death. Transition probabilities for overall survival and relapse incidence were derived from the MORPHO trial. Relapse incidence for salvage regimens were derived from other trials and observational studies. Salvage therapies were taken from ADMIRAL trial (Perl et al) and included Fludarabine/Cytarabine/G-CSF/Idarubicin (FLAG-Ida), Mitoxantrone/Etoposide/Cytarabine (MEC) (MEC), FLT3 inhibitors (gilteritinib), donor lymphocyte infusion (DLI), and second HCT. Where data were unavailable, probabilities were derived from institutional data and expert opinion. Costs were estimated from a U.S. health care sector perspective using publicly available sources, including the Federal Supply Schedule for pharmaceutical pricing. Utility weights were drawn from literature on AML, including the MORPHO trial (Hamilton et al), and post-HCT quality of life. With 1 being a perfect health state and 0 being equivalent to death, the median post-HCT health state utility value was 0.8 in the relapse-free survival state and 0.6 in the relapsed state. Disutility values were used to account for adverse effects related to salvage chemotherapy, DLI, and second HCT. The time horizon of 36 months post-HCT was selected to reflect the high amount of censoring in the MORPHO trial data after that time point. A 3.0% annual discount rate was applied for both costs and quality-adjusted life-years. The primary outcomes were the incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (iNMB), expressed in 2025 U.S. dollars per quality-adjusted life-year. These outcomes were evaluated at a willingness-to-pay threshold of $100,000 per QALY that was selected based on standard modeling practices in the U.S. context. Sensitivity analyses were performed to validate the model.

Results: In the base case analysis, patients receiving gilteritinib maintenance for post-HCT MRD-positive FLT3-ITD AML gained an average of 1.93 quality-adjusted life-years (QALYs) over 3 years at a cost of $376,825 compared to 1.75 QALYs at a cost of $152,393 for patients not receiving post-HCT maintenance therapy. The ICER was $1,209,667 per QALY and the iNMB was -$205,879. Given that the ICER was greater than the willingness-to-pay threshold of $100,000 per QALY and the iNMB was less than zero, post-HCT gilteritinib maintenance therapy was determined to not be cost-effective.

In a probabilistic sensitivity analysis, gilteritinib maintenance was cost-effective in 0 of 1,000 simulations. The maximum price for monthly gilteritinib to be cost-effective was $1,326, compared to a federal contract rate of $19,756. Patients gained a net 0.19 QALYs (approximately 2.3 full-quality months of life) with gilteritinib maintenance. At current prices, patients receiving gilteritinib maintenance would need to gain 2.24 QALYs more than patients not receiving Gilteritinib maintenance to be cost-effective.Conclusions: We found that gilteritinib maintenance was not cost-effective in a population with post-HCT MRD-positive FLT3-ITD AML. There was a large discrepancy in nets costs and effectiveness, suggesting that gilteritinib prices could be lowered to better reflect the incremental improvement in clinical outcomes.

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2025
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