Treatment Patterns and Healthcare Resource Utilization in Patients with FLT3-Mut and FLT3-Wt Acute Myeloid Leukemia: A Multi-Country Medical Chart Study

Introduction: FLT3 is a frequently mutated gene in acute myeloid leukemia (AML) with two main types of mutations: internal tandem duplication (ITD) and point mutations in the tyrosine kinase domain (TKD). FLT-mut AML is associated with poor prognosis. With the development of new therapies in AML, especially those targeting FLT3-mut, there is a need to understand the current treatment (tx) patterns and healthcare resource utilization (HRU) among AML patients. The current study used real-world data from medical records to evaluate tx patterns and HRU among adult AML patients.

Methods: Hematologists and oncologists were recruited from 10 countries (US, Canada, UK, France, Germany, Italy, Spain, Netherlands, Japan, and South Korea) from an established physician panel. Eligible patients were randomly selected by physicians and were categorized into 6 cohorts: 1) newly diagnosed (ND) FLT3-mut patients <65, 2) ND FLT3-mut patients ≥65, 3) ND FLT3-wild type (FLT3-wt) patients <65, 4) ND FLT3-wt patients ≥65, 5) relapsed/refractory (R/R) FLT3-mut patients, and 6) R/R FLT3-wt patients. The index date was defined as the date of initiation of first AML therapy for ND patients, and the date of R/R classification for R/R patients. FLT3-mut was based on the genetic test closest to the index date. FLT3-mut and FLT3-wt patients may harbor mutations in other genes. Baseline characteristics, tx patterns, and AML-related HRU were collected and described for each cohort.

Results: The study included 1,027 AML patients-183 FLT3-mut and 186 FLT3-wt ND patients <65, 136 and 159 ND patients ≥65, and 181 and 182 R/R patients. Mean age was 48.2 and 72.3 for ND patients <65 and ≥65; among R/R patients, mean age of FLT3-mut patients was younger than FLT3-wt patients (53.2 vs. 56.8). Among FLT3-mut patients, 70.0% had ITD and 42.4% had TKD mutations. The study identified substantial heterogeneity in tx pattern for AML. Among ND patients <65, the most common initial tx was standard-to-intermediate dose cytarabine (SDAC)-based therapies (43.2 and 55.9% for FLT3-mut and FLT3-wt), followed by hypomethylating agent (HMA)-based therapies (13.7 and 11.8%). Among ND patients ≥65, the most common initial tx were HMA-based therapies (36.0 and 47.2%), followed by SDAC-based therapies (30.1 and 30.8%). Among R/R patients, the most common initial tx after R/R was BSC only (39.8 and 24.7%), followed by SDAC-based therapies (12.7 and 19.2%), HMA-based therapies (9.4 and 16.5%), and low dose cytarabine-based therapies (9.4 and 15.4%). About 20-60% ND patients and 40% R/R patients received non-guideline recommended tx. Among ND patients, tx for FLT3-mut patients tended to be more aggressive than for FLT3-wt patients. For patients <65, FLT3-mut patients used more high-dose cytarabine-based therapies than FLT3-wt patients (13.7 vs 9.7%); for patients ≥65, fewer FLT3-mut patients used HMA-based therapies than FLT3-wt patients (36.0 vs 47.2%). The proportion of patients who received stem cell transplant was higher in FLT3-mut vs. FLT3-wt patients (ND<65: 29.2 vs. 24.3%; ND≥65: 13.6 vs. 8.5%; R/R: 23.6 vs. 18.1%). In addition, this study demonstrated that AML patients had extensive HRU. The average rate of hospitalization across all cohorts during the event-free period (i.e., the period free of R/R for ND cohorts or before next R/R for R/R cohorts) was 0.27 hosp/mo (5.4 d/mo), while the rate during the post-event period was 0.52 hosp/mo (6.5 d/mo). The average number of days of intensive care unit stays was 0.28 d/mo for the event-free period and 0.50 d/mo for the post-event period. For emergency department visits, the average rate was 0.23 visits/mo during the event-free period and 0.54 visits/mo during the post-event period. During both event-free and post-event periods, patients across all cohorts also experienced frequent outpatient visits, blood transfusions, and received extensive tx for infections.

Conclusions: Using real-world data of AML patients in multiple countries, this study reveals a considerable amount of heterogeneity of tx pattern, including many tx not consistent with tx guidelines. FLT3-mut patients tended to receive more aggressive tx, consistent with fact that the mutation confers a poor prognosis. It also demonstrates extensive HRU among these patients, particularly among R/R cohorts. The study provides timely evidence to understand the current tx landscape and to highlight the substantial unmet needs among AML patients.