Healthcare Utilization and Imputed Costs of Acute Myeloid Leukemia Patients By FLT3 Status and Early Midostaurin Use at a Comprehensive Cancer Center
Authors: Yoo Minkyoung , Menon Jyothi , Willis Connor , Unni Sudhir , Au Trang , Biskupiak Joseph , Ndife Briana , Joseph George J , Bonifacio Gaetano J , Stein Eytan M. , Tantravahi Srinivas K. , Shami Paul J. , Kovacsovics Tibor , Brixner Diana , Stenehjem David Dean 
Published: October 2019

Abstract
INTRODUCTION: Mutation of FLT3, a tyrosine kinase receptor, is one of the most common molecular alterations in AML. In 2017, the FDA approved midostaurin for treatment of newly diagnosed AML adult patients with FLT3 mutation. Understanding of utilization and costs associated with AML pre and post Midostaurin approval is warranted. The objectives of this study were to evaluate healthcare utilization and costs between FLT3-mutated AML patients and FLT3-wildtype AML patients, pre-midostaurin approval and among initial FLT3-mutated AML patients treated with midostaurin.
METHODS: FLT3-tested AML patients treated with 7+3 induction chemotherapy prior to midostaurin approval, were identified retrospectively from 2007-2016 at Huntsman Cancer Institute. A separate sample of FLT3-mutated patients treated with midostaurin from May 2017 to June 2018 were also identified. Healthcare charges, which are the individual list prices set by the medical facility, were computed for inpatient, outpatient and emergency services in this study. Since cost data were not available, charges were converted to imputed costs by applying the 2013 CMS charge-to-cost ratio of 0.492. Health care utilization through inpatient, outpatient and emergency room visits were also evaluated for FLT3-mutated and FLT3-wildtype patients.
RESULTS: Pre-midostaurin: One hundred patients (39 FLT3-mutated, 61 FLT3-wildtype) prior to the availability of midostaurin were identified with a median age of 53 years. Median number of AML related inpatient visits for the total sample was 5 (FLT3-mutated [5] vs FLT3-wildtype [6] p=0.1]. Median outpatient visits were 43 for the total sample (FLT-mutated [47] vs FLT3-wildtype [51], p=0.4).
Healthcare costs were categorized as AML related and all-cause related costs. AML related costs, which included transplant costs, contributed to nearly 70% of all-cause healthcare costs on an average. Approximately 38% of total AML-related costs were attributable to induction therapy among FLT3-mutated patients, while 29% of total AML-related costs among wildtype patients were related to induction (p<0.001). FLT3-mutated patients had 35% higher mean total AML-related costs (Table 1). This was mainly due to higher inpatient costs for FLT3-mutated as compared to FLT3-wildtype patients. Among types of costs, physician costs were significantly higher for FLT3-mutated patients as compared to FLT3-wildtype patients (Table 1). Facility and pharmacy costs were similar for both groups (Table 1).
Midostaurin cohort: Five FLT3-mutated patients administered midostaurin during induction treatment were identified from 2017 and 2018. No significant differences were observed in health care utilization between pre-midostaurin FLT3-mutated patients and midostaurin-treated patients. Midostaurin-treated patients and pre-midostaurin FLT3-mutated patients had similar mean AML-related healthcare costs, with a downward trend in costs among midostaurin patients (Table 1). Majority of costs in both groups were incurred during inpatient setting. Approximately 32% of costs in both groups were attributable to physician or professional costs (Table 1).
CONCLUSIONS:
No significant differences were observed in healthcare utilization or imputed costs among FLT3-mutated patients before and after midostaurin approval. Patients with FLT3 mutations historically had higher health care utilization and costs, likely due to generally poorer prognosis, increased transplant rates and higher relapse rates associated with this mutation. Inpatient costs were higher for FLT3-mutated patients, mainly due to higher physician costs.
The change in standard of care for patients with FLT3 mutations following the addition of midostaurin to 7+3 did not result in increased healthcare utilization or costs. However, the sample size for the midostaurin-treated patients was very small in this early analysis. Thus, these conclusions are preliminary in nature.
SPONSORSHIP: Funding for this study was provided by Novartis Pharmaceuticals.

Disclosures
Unni: Novartis: Research Funding. Biskupiak:Novartis: Research Funding. Ndife:Novartis: Employment. Joseph:Amgen: Equity Ownership; Novartis Pharmaceuticals Corporation: Employment; Pfizer: Equity Ownership; Express Scripts: Equity Ownership. Bonifacio:Novartis: Employment. Stein:Agios: Consultancy; Bayer: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Celgene: Consultancy. Shami:JSK Therapeutics: Employment, Other: stock ownership; Lone Star Thiotherapies: Other: stock ownership. Kovacsovics:Amgen: Honoraria, Research Funding; Abbvie: Research Funding. Brixner:University of Utah: Research Funding; Millcreek Outcomes Group: Equity Ownership; Gilead: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy; Abbott: Consultancy; BD: Consultancy. Stenehjem:Novartis: Research Funding.