Treatment Patterns and Healthcare Resource Utilization in Patients with Relapsed/Refractory Acute Myeloid Leukemia and a Subset with IDH1-Mutation: A United States Medical Chart Review Study

Introduction: In the United States (US), acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Patients with relapsed or refractory AML (R/R) have a particularly poor prognosis, and more effective and less toxic treatments are urgently needed. The gene encoding isocitrate dehydrogenase 1 (IDH1) is mutated in 6-10% of AML patients. Drugs that target the altered enzyme have shown significant clinical activity in the R/R setting, with the first such agent, ivosidenib, recently receiving FDA approval. We conducted a retrospective chart review to evaluate current treatments and healthcare resource use in an R/R AML population, with a sub-analysis focusing on the population with IDH1 mutations (mIDH1). Findings from this study will help to better understand the future impact of targeted IDH1 inhibitors in this difficult-to-treat patient population.

Methods:US-based hematologists and oncologists were recruited from existing physician panels to extract information from eligible patients' medical charts. Each physician extracted information, including patient demographics, medical history, AML treatment, and AML-related healthcare resource use. Eligible patients must have been initially diagnosed with R/R AML and tested for mIDH1 between January 2012 and June 2017. Patients were excluded if they had ever been enrolled in a clinical trial for an IDH1 inhibitor. The index date was defined as the date of initial R/R diagnosis and information was collected through end of follow-up, defined as the end date of care, date of death, or date of data collection, whichever occurred first. Patient characteristics, treatments, and AML-related healthcare resource use were described. mIDH1 patients were oversampled to achieve the targeted sample size of 300 patient charts, evenly split between mIDH1-positive and IDH1 wild type (wt) patients. As a result, findings reported for the overall patient population were reweighted to reflect an 8.0% prevalence of mIDH1.

Results:Data were collected from 182 oncologists/hematologists, providing chart information for 304 patients (154 mIDH1-positivepatients and 150 mIDH1-negativepatients). Median follow-up time for all patients was 11.1 months. After reweighting, the mean age for the overall patient population was 57.7 years old and most patients were first diagnosed with de novoAML (92.8%), as opposed to secondary AML (7.2%). The population had a higher percentage of relapsed patients than primary refractory patients (73.7% versus 26.3%) and a higher percentage of patients treated in a community-based setting than an academic-based setting (64.2% versus 35.8%).

After the initial diagnosis of R/R AML, 90.9% of all patients received some type of active treatment, with intensive chemotherapy being the most common initial treatment (65.0%), followed by less-intensive chemotherapy regimens (19.3%), and hypomethylating agents (14.9%). 44.8% and 11.0% of patients also received a second- or third-line treatment regimen, respectively. 10.4% of patients received a stem cell transplant during the follow-up period.

There was significant health resource utilization in this population. 82.0% of patients had at least one inpatient admission during the follow-up period, with the overall population averaging 0.28 admissions per-patient-per-month. The most common reason for AML-related inpatient admissions was chemotherapy administration. 66.4% of patients were hospitalized for treatment administration, 31.8% for infections, and 27.1% for febrile neutropenia. In addition, 39.6% of patients had at least one emergency room (ER) visit and 14.2% of patients had at least one intensive care unit (ICU) admission. The treatment and healthcare resource use burden was similarly high for the subset of mIDH1-positive patients. No significant differences were found between the mIDH1-positive and IDH1 wtpatients.

Conclusions:Using retrospective medical chart data, this study highlights current treatment and healthcare resource use for adult patients with R/R AML. There is a high burden associated with R/R AML due to the health issues associated with rapidly progressive disease and the toxicity of available treatments, which require inpatient admissions. As more targeted drugs become available for patients in the R/R setting, such as ivosidenib, it will be of interest to re-evaluate the burden and clinical outcomes in the R/R AML population.