Healthcare resource utilization and cost of molecular targeted versus non-targeted therapies in acute myeloid leukemia Free

Background Molecular targeted therapies (MTTs) have provided new treatment options for patients with Acute myeloid leukemia (AML) with molecular mutations demonstrating clinical benefits even without complete remission. However, the economic impact of MTTs in real-world settings remains uncertain. This study aims to evaluate the cost and healthcare resource utilization (HCRU) associated with MTT in AML patients with actionable mutations. Specifically, we sought to determine whether MTTs reduce HCRU, how their associated costs compare to non-targeted therapies, and whether clinical advantages justify the economic trade-offs. Specifically, we sought to determine whether MTTs reduce HCRU, how their associated costs compare to non-targeted therapies, and whether clinical advantages justify the economic trade-offs. We also examined the role of treatment setting and cost components, such as acute care, outpatient services, and pharmacy use.

Methods This retrospective cohort study utilized two data sources. The Symphony Health Integrated Dataverse, linked with genomic data, identified patients ≥45 years with ≥1 AML diagnosis (July 2018-December 2024) and ≥6 months of continuous enrollment prior to treatment initiation. The Merative MarketScan database (January 2006–December 2024) provided average reimbursed costs per HCRU event.

We examined AML-related HCRU and costs over a 12-month period following treatment initiation. Patients were categorized into two sub-cohorts: (1) those receiving MTT (ivosidenib, enasidenib, midostaurin, gilteritinib) and (2) biomarker-positive patients (IDH1, IDH2, FLT3) treated only with non-MTT. Sub-cohorts were reweighted using entropy balancing to adjust for age, sex, geographic region, insurance type, and Elixhauser Comorbidity Index.

Mean costs from the closed claims data were applied to each weighted HCRU event observed in the open claims cohort. Final per member per month (PMPM) costs were calculated for each

sub-cohort to facilitate comparison of economic burden across treatment strategies. Zero-inflated Negative Binomial and Tweedi distributions were used to determine the statistical significances of the difference in HCRU and costs between the sub-cohorts respectively.

Results Among patients identified through open claims data, 2,692 individuals diagnosed with acute myeloid leukemia (AML) received molecularly targeted therapies (MTTs), of whom 57% were male and 43% were female, with a median age of 65 years. Additionally, 548 biomarker-positive patients were treated with non-MTT regimens (53% male, 47% female; median age: 71), while 593 biomarker-positive patients did not receive any treatment.

Healthcare resource utilization (HCRU), measured as events per 1,000 patients per year, was significantly lower in the MTT cohort compared to the non-MTT cohort for both acute care episodes (MTT: 946; non-MTT: 1,084; p < 0.01) and outpatient visits (MTT: 9,865; non-MTT: 11,741; p < 0.01).

Despite reduced utilization, the mean reimbursed cost per acute care episode was higher in the MTT cohort ($116,414) compared to the non-MTT cohort ($80,356; p < 0.01). In contrast, the average cost per outpatient visit was significantly lower for MTT-treated patients ($1,245) than for those receiving non-MTT regimens ($1,496; p < 0.01).

When combining utilization rates with unit costs, total monthly acute care expenditures per 1,000 patients were $9,177,304 in the MTT group versus $7,258,870 in the non-MTT group (p < 0.01). Outpatient costs followed an inverse trend, with lower total expenditures observed in the MTT group ($1,023,831) compared to the non-MTT group ($1,463,858; p < 0.01).

Notably, AML-related monthly outpatient pharmacy costs per 1,000 patients were substantially higher among MTT recipients ($12,229,000) compared to those receiving non-MTTs ($2,576,020; p < 0.01).

Overall, total AML-related monthly costs per 1,000 patients were $22,429,905 for the MTT cohort versus $11,298,748 for the non-MTT cohort (p < 0.01), with the cost differential predominantly driven by elevated pharmacy expenditures in the MTT group.

Conclusions: For AML patients with actionable molecular mutations, treatment with MTTs results in reduced healthcare utilization but increased total costs, primarily due to drug expenses. These findings emphasize the economic trade-offs in precision oncology and highlight the necessity for strategies to enhance the cost-effectiveness of MTTs in routine care.