Real-World Patterns of Molecular Genetic Testing Among Patients with Acute Myeloid Leukemia in US Community Oncology Settings

Introduction: Molecular genetic testing is essential to inform disease diagnosis, prognosis, and treatment selection for patients with acute myeloid leukemia (AML). The standard treatment is induction chemotherapy followed by post-remission consolidation therapy including chemotherapy and allogeneic hematopoietic stem cell transplantation. Since May 2017, targeted therapies such as midostaurin, ivosidenib, enasidenib, and gemtuzumab ozogamicin were introduced for the treatment of AML. The use of targeted therapies is driven in part by the results of molecular genetic testing. The aim of this study was to determine molecular genetic testing utilization among patients with AML before and after the introduction of targeted therapies in May 2017 within community oncology clinics.

Methods: A retrospective observational cohort study was conducted using de-identified data from The US Oncology Network iKnowMed electronic health record database and chart review. The iKnowMed is an oncology-specific system that captures outpatient practice encounter history for patients under care, including (but not limited to) laboratory tests, diagnosis, therapy administration, line of therapy, staging, and performance status information. These structured data were supplemented by targeted chart review to capture unstructured data. All patients aged 18 years or older with newly diagnosed or relapsed/refractory AML who received treatment in The US Oncology Network from January 2014 through February 2019 were included in the study cohort. Patients enrolled in clinical trials were excluded. Patients were classified into two groups: those who received treatment prior to May 2017 and those who received it after May 2017. Molecular genetic testing included IDH1, IDH2, FLT3-ITD, FLT3-TDK and CD33 genes. We assessed the proportion of newly diagnosed or relapsed/refractory AML patients who received molecular genetic testing in the inpatient setting, outpatient setting and prior to treatment initiation before and after May 2017.

Results: The study population consisted of 434 patients diagnosed with AML, of whom 313 had newly diagnosed and 121 had relapsed/refractory AML. The median age of the study cohort was 73 (interquartile range: 63.0, 79.0) years. Most of the study cohort were male (57.6%, n=250) and Caucasian (77.0%, n=334). Approximately 75% (235/313) of newly diagnosed patients (75.1%; 235/313) and 81.0% (98/121) of patients with relapsed/refractory AML had molecular genetic testing. The proportion of patients who had molecular genetic testing before and after May 2017 were similar for newly diagnosed AML patients (72.2% vs. 78.1%; p=0.2260) and relapsed/refractory AML patients (80.0% vs. 83.9%; p=0.6357). The proportion of newly diagnosed AML patients who received molecular genetic testing in the inpatient setting (18.5% vs. 23.8%; p=0.3403) and outpatient setting (49.4% vs. 51.0%; p=0.4223) did not change before and after May 2017. Likewise, among patients with relapsed/refractory AML, the proportion of molecular genetic testing in the inpatient setting (31.1% vs. 35.5%; p=0.8523) and outpatient setting (44.4% vs. 51.6%; p=0.7749) were similar before and after May 2017. In addition, the proportion of newly diagnosed AML patients (55.6% vs. 62.9%; p=0.3835) and relapsed/refractory AML patients (45.6% vs. 61.3%; p=0.3063) who received molecular genetic testing prior to AML treatment initiation did not change before and after May 2017. Time from test order date to test result availability was not significantly different before [mean (SD) =9.3 days (16.8)] and after May 2017 [mean (SD)=9.0 days (9.9)].

Conclusion: Introduction of targeted therapies for AML did not increase molecular genetic testing rates nor improve the turnaround time for test result availability in newly diagnosed and relapsed refractory AML patients by February 2019. Two out of 5 patients did not have molecular genetic testing performed prior to initiation of AML therapy after May 2017 when targeted therapies became available. Patients age, comorbidities and drug access issues may have contributed to under-utilization of molecular genetic testing. Further research is needed to identify barriers to molecular genetic testing in patients with AML.