Screening a Targeted Panel of Genes by Next-Generation Sequencing Improves Risk Stratification in Real World Patients with Acute Myeloid Leukemia

SIMPLE SUMMARY: In this study, we prospectively analyzed a cohort of 268 newly diagnosed AML patients with the objective of assessing the clinical value of screening a targeted gene panel by next-generation sequencing (NGS). We found that access to NGS data refined risk assessment for 62 patients, corresponding to approximately 23% of the study population. We further compared clinical outcomes with prognostic stratification, and observed unexpected results associated with mutations in the FLT3 gene, highlighting the need for further improvements in current risk classification criteria. ABSTRACT: Although mutation profiling of defined genes is recommended for classification of acute myeloid leukemia (AML) patients, screening of targeted gene panels using next-generation sequencing (NGS) is not always routinely used as standard of care. The objective of this study was to prospectively assess whether extended molecular monitoring using NGS adds clinical value for risk assessment in real-world AML patients. We analyzed a cohort of 268 newly diagnosed AML patients. We compared the prognostic stratification of our study population according to the European LeukemiaNet recommendations, before and after the incorporation of the extended mutational profile information obtained by NGS. Without access to NGS data, 63 patients (23%) failed to be stratified into risk groups. After NGS data, only 27 patients (10%) failed risk stratification. Another 33 patients were re-classified as adverse-risk patients once the NGS data was incorporated. In total, access to NGS data refined risk assessment for 62 patients (23%). We further compared clinical outcomes with prognostic stratification, and observed unexpected outcomes associated with FLT3 mutations. In conclusion, this study demonstrates the prognostic utility of screening AML patients for multiple gene mutations by NGS and underscores the need for further studies to refine the current risk classification criteria.