Treatment Patterns and Healthcare Resource Utilization (HRU) in Patients with Relapsed/Refractory (R/R) FLT3-Mutated (FLT3mut) and FLT3-Wild Type (FLT3wt) Acute Myeloid Leukemia (AML): A Multi-Country Medical Chart Study
Authors: Griffin James D. , Shah Manasee V , Song Yan , Yang Hongbo 
Published: October 2019

Abstract
Background: Salvage therapy for patients with R/R AML has long relied on chemotherapy as a bridge to hematopoietic stem cell transplantation (HSCT). With the advent of treatments targeted to biomarkers, such as fms-like tyrosine kinase 3 (FLT3), there is a need to understand current treatment patterns and HRU. This multi-country study utilized real-world evidence (RWE) collected from medical charts to evaluate treatment patterns and HRU among patients with R/R AML by FLT3 mutation status.
Methods: Hematologists/oncologists were recruited from 10 countries (US, Canada, UK, France, Germany, Italy, Spain, Netherlands, Japan, and South Korea). Patients with AML who were classified as relapsed or refractory to initial treatment between January 1, 2013 and December 31, 2015 were eligible for inclusion. Eligible patients with R/R AML were randomly selected by physicians and were categorized into one of two cohorts: FLT3mut or FLT3wt patients. Stratified recruitment was used to ensure that an equal ratio of FLT3mut and FLT3wt patients were enrolled. The index dates were defined as the dates of R/R classification and data collection until the date of last follow-up or death.
Results: The study included both FLT3mut (n=181) and FLT3wt (n=182) patients. Of the FLT3mut patients, 53.6% (n=97) had only an internal tandem duplication (ITD) mutation, 15.5% (n=28) had both ITD and tyrosine kinase domain (TKD) mutations, and 30.9% (n=56) only had a TKD mutation. Other mutations (eg, NPM1, IDH1/2, CEBPA, KIT, AXL) were seen in both cohorts; all other mutations were more common in FLT3mut patients. Compared with FLT3wt patients, FLT3mut patients were significantly younger at the event date (53.2 ± 15.2 vs 56.8 ± 14.6, P<.05) and more had an Eastern Cooperative Oncology Group score ≥2 (36.9% vs 33.0%; P<.01). FLT3mut patients were also more likely to have dysplasia-related AML (22.8% vs 12.6%; P<.01) and genetic abnormalities (38.9% vs 16.1%; P<.01) than FLT3wt patients.
Despite treatment guidelines, which recommend specific chemotherapy-based regimens according to patient age and health status, nearly one-third of patients with R/R AML received only best supportive care (BSC) after being classified as R/R AML; more FLT3mut patients received BSC (39.8%) than FLT3wt patients (24.7%). While few patients received a FLT3 inhibitor (eg, midostaurin), this is most likely due to limited availability outside of a clinical trial. Overall, 20.8% of patients with R/R AML received some type of transplant; the rate of HSCT was similar between cohorts.
Patients with R/R AML were high utilizers of healthcare resources. In the post-event period, patients averaged 0.52 hospital visits per month with a mean length of stay (LOS) of 16.6 days/visit and a mean LOS of 6.8 days/month; there was no significant difference between FLT3mut and FLT3wt cohorts. The mean number of pre-event intensive care unit (ICU) visits was 0.03 ± 0.15 with a mean LOS/visit of 10.8 ± 9.6. In the post-event period, the mean number of ICU visits was 0.16 ± 1.3 with a mean LOS of 7.5 ± 6.5 days/visit. In total, 30.1% of all patients with R/R AML had hospice care in the post-event period; the mean number of days in hospice was 4.1 ± 8.7 days (4.5 ± 9.7 days [FLT3mut] vs 3.8 ± 7.7 [FLT3wt]). In some instances in the pre-event period, patients with FLT3mut were higher users of healthcare resources. Compared with FLT3wt, patients with FLT3mut had a longer hospital LOS/visit (29.6 days vs 21.8 days; P<.05) and had significantly higher utilization of all types of outpatient visits, including: total outpatient, hematologist, nurse, and general practitioner (all P<.001).
Conclusions: Utilizing RWE, these data reveal that patients with FLT3mut AML are diagnosed at an earlier age and utilize more healthcare resources than patients with FLT3wt AML. Further, for patients with R/R AML, regardless of mutation status and despite the availability of effective therapies, the most common treatment was BSC - a divergence from accepted treatment guidelines. Additionally, the breadth of treatments being used suggests that there is no real standard of care for patients with R/R AML. The availability of targeted agents (ie, FLT3 inhibitors) may provide treatment options for patients.

Disclosures
Griffin: Novartis Pharma: Other: Grant, Patents & Royalties: Royalties ; Sun Pharmaceuticals: Consultancy; Lilly Pharmaceuticals: Other: Grant; Myeloproliferative Neoplasia Foundation: Other: Grant ; Analysis Group: Consultancy; RXi Pharmaceuticals: Consultancy; Astellas Pharma: Consultancy. Shah:Astellas Pharma: Employment. Song:Astellas Pharma: Consultancy. Yang:Astellas Pharma: Consultancy.