Socioeconomic cost of AML in Sweden—A population‐based study using multiple nation‐wide registers

Abstract Acute myeloid leukemia (AML) is associated with a high economic and clinical burden. Recently novel therapies have been added to standard treatment regimens. Here, we evaluated the economic impact of AML up until the introduction of these novel therapies. Individual data on 2954 adult patients diagnosed from 2007 to 2015 from five Swedish national population‐based registers were used, enabling analyses from diagnosis to either death or 5‐year follow‐up for survival, inpatient and outpatient costs, costs of prescribed drugs, sick leave, and early retirement. Costs per patient were stratified by age group, treatment options, and FLT3‐ITD status. The expected 5‐year costs per patient differed substantially between age groups. Patients aged 18–59 years had an expected mean cost per patient of €170,748, while age groups 60–69 years, 70–79 years, and >80 years incurred an expected mean cost of €92,252, €48,344, and €24,118, respectively, over 5 years. Patients <60 years undergoing stem cell transplantation had the highest costs (€228,525 over 5 years). About 60% of costs for these patients were from hospitalizations and 20% from sick leave and early retirement; cost per day was highest from the first admission to complete remission. This study provides a baseline for socioeconomic evaluations of novel therapies in AML in Sweden.

For many years, the cost of anti-leukemia drugs has been low due to the lack of novel therapeutics. On the other hand, the severe toxicity from intensive chemotherapy leads to long and repeated hospitalizations and the need for extensive supportive care including blood transfusions and anti-infective drugs. There are also high expenses associated with alloSCT, including searches for and cell harvests from suitable donors.
Although HMAs are more expensive, and complete remission (CR) rates and overall survival are low, their relatively low toxicity enables treatment in an outpatient setting. A significant proportion of elderly patients receive palliation only, with lower drug costs and shortened residual life span [3,8].
Recently, a number of new targeted and nontargeted oral therapies, such as FLT3 inhibitors, with low toxicity have been developed [17,18] showing efficacy as monotherapy or in combination with chemotherapies or HMAs. These drugs will likely be used in various treatment combinations, adding to costs of drug therapy, but also leading to improved outcomes for patients.
Studies addressing the cost and burden of AML are sparse; few of these report costs outside the US setting [19][20][21][22][23][24][25][26][27], and none are population based. This study provides a baseline for economic evaluations of novel therapies in AML in Sweden.

Study design
The study population in this noninterventional retrospective register study consists of adult patients diagnosed with AML in Swe- The index date was defined as the diagnosis date in the SCR, the date of the sampling of the first diagnostic test defining AML. Analyses were performed in the postindex period, which varied in length from a minimum of 6 months to a maximum of 9 years. Subjects were right-censored at end of follow-up defined as 5 years after the date of diagnosis or end of data availability, whichever occurred first.
In the analyses of costs per treatment phase, a start event (e.g., first CR) and an end event (e.g., relapse, SCT, death, or end-of-data, whichever occurred first) were defined, and total costs and mean length of the respective treatment phase were estimated.
Information on FLT3-ITD mutation was recorded in the Swedish National AML Registry (SwAMLR). It should be noted that other FLT3 mutations, such as point mutations, were not recorded.

Data sources
Data were retrieved from five national registers: the SCR, the National

Analysis
Survival was analyzed using standard Kaplan-Meier survival estima-

RESULTS
A total of 2954 adult patients aged ≥18 years were identified with an AML diagnosis in the SCR. A detailed description of the patient population, including subgroups, is presented in Table 1

Expected costs by treatment
In Figure 2

Expected costs for alloSCT and non-SCT patients up to 60 years of age
The subgroup of patients <60 years achieving first CR after highdose chemotherapy and undergoing alloSCT within the first year, and before the first relapse, was stratified by SCT status for the analysis For costs attributable to outpatient visits, prescribed medication and early retirement costs were approximately threefold for the group of patients undergoing SCT compared to those not undergoing SCT. After 24 months, the cumulative cost for SCT patients increased more than for non-SCT patients.  Table 1). Expected accumulated costs were slightly higher in the FLT3-ITD positive group (Figure 4)

Expected costs by survival time
In Figure

Costs by treatment phase
In addition to the analyses of expected accumulated cost from diagnosis until 5 years thereafter, analyses of costs in different treatment phases were performed.
The analysis from the first admission to CR included 1243 patients.
The mean number of days from first day of the first admission to CR was 45 and mean total costs during this time amounted to €23,086. For The highest total mean cost was found in patients undergoing SCT.
Patients were followed from the day of transplantation until death, end-of-data, or a maximum of 5 years for a mean of 844 days. The total mean cost incurred was estimated to €137,209 per patient.
The mean cost per day and mean number of days for the respective treatment phases are depicted in Figure 6. The area under the curve represents the total cost during the treatment phase. As expected, costs were higher during induction treatment at the beginning of the treatment course. Total costs were found to be highest when resource use and associated costs were incurred over a longer time, as observed in patients undergoing SCT.

DISCUSSION
Here

DATA AVAILABILITY STATEMENT
Data cannot be shared due to restrictions in ethical permission and data privacy regulations from the data holders.