Cost-Effectiveness of Midostaurin in the Treatment of Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia in the United States

Introduction

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and is fatal if left untreated. Patients with FLT3-mutated AML account for approximately one-third of all AML patients and have a poorer prognosis than patients with FLT3 wild-type AML. Midostaurin has been shown to effectively improve overall survival (OS) and event-free survival (EFS) compared to existing regimens among newly diagnosed FLT3-mutated AML patients in the Phase III randomized controlled RATIFY trial. The current study aimed to assess the cost-effectiveness of midostaurin + cytarabine + daunorubicin (midostaurin arm) versus placebo + cytarabine + daunorubicin (placebo arm), considering direct medical costs and treatment benefits, in the treatment of adult patients newly diagnosed with FLT3-mutated AML who are eligible for standard cytarabine + daunorubicin chemotherapy from a US third-party payer perspective.

Methods

Costs and benefits associated with the midostaurin arm and the placebo arm were estimated based on a partitioned survival model with four health states (active disease, complete remission [CR], relapse, and death) over a lifetime. Efficacy inputs (time to CR or death, time to relapse or death, and OS) for the two treatment arms were estimated using the RATIFY trial data. OS rates were adjusted using natural US mortality rates. Treatment costs (including drug and drug administration costs and hospitalization costs for induction and consolidation therapies), drug monitoring costs, stem cell transplant (SCT) procedure costs, adverse event (AE) costs, and medical costs associated with health states were obtained from publicly available databases, literature, and real-world database analysis. All costs were inflated to 2016 USD. Health state utilities were estimated based on a de novo utility study and expert opinions. Incremental costs per quality-adjusted life year (QALY) and life year (LY) gained were estimated comparing the midostaurin versus placebo arm. Deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of the model.

Results

Compared to the placebo arm, patients in the midostaurin arm incurred higher total direct costs ($4,043,470 vs. $3,959,741) over a lifetime. Specifically, the midostaurin arm was associated with higher treatment and monitoring costs ($251,883 vs. $187,282), higher medical costs associated with health states (due to longer OS; $3,523,343 vs. $3,500,095), lower SCT procedure costs (due to lower cumulative SCT rate in the midostaurin arm vs. the placebo arm in the RATIFY trial; $155,794 vs. $157,423), lower terminal care costs ($57,239 vs. $61,389), and higher AE costs ($55,210 vs. $53,551). Modeling efficacy based on the RATIFY trial, the midostaurin arm was associated with more LYs (11.44 vs. 9.85), and more QALYs (7.30 vs. 5.94) over a lifetime. In the model, when cost and effectiveness outcomes were combined, the midostaurin arm led to an incremental cost per LY gained of $52,596, and an incremental cost per QALY gained of $61,167 compared to the placebo arm over a lifetime. DSA results showed that the estimated incremental cost-effectiveness ratio (ICER) was generally consistent with the base case result. The model was most sensitive to the methods used to estimate efficacy outcomes, but not sensitive to the variations in midostaurin drug costs, other treatment costs, medical costs, and utility values. Results from the PSA based on the base case scenario showed that the probability of the midostaurin arm to be cost-effective compared to the placebo arm was 69.0% at a willingness to pay (WTP) of $175,000. In scenario analyses where cost effectiveness was modeled under the assumption that midostaurin was not used in the post-consolidation setting, midostaurin continued to be cost-effective compared to the placebo arm. In fact, it was shown to be the dominant strategy (i.e., the midostaurin arm was associated with lower costs and better effectiveness).

Conclusions

Compared to the placebo arm, the midostaurin arm has a relatively low ICER over a lifetime, and thus should be considered as a cost-effective strategy in the treatment of adult patients with newly diagnosed FLT3-mutated AML from a US third-party payer perspective.