Abstract 2204: Predicting survival outcomes in patients with acute myeloid leukemia: medium-sized versus large next-generation sequencing panels
Cancer Research(2023)
摘要
Abstract Background: Next-generation sequencing (NGS) multigene panels allow the identification of genetic variants in patients with acute myeloid leukemia (AML). This study assessed the effect of the NGS panel size on positivity rate and clinic utility in helping predict survival outcomes. Design: This is a retrospective study of AML patients (n=76) who underwent both diagnostic and post-treatment testing with a large 220-gene NGS assay. Mutation profiles and measurable residual disease (MRD) status were assessed with the large panel or a subset of the genes on the panel (i.e., a medium-sized panel with 42 genes); MRD assessment excluded DTA mutations (i.e., mutations in preleukemic genes DNMT3A, TET2 and ASXL1). Kaplan-Meier method was used to compare overall survival between MRD positive and negative patients. Results: The 76 patients evaluated were diagnosed with de novo AML (n=69) or secondary AML (n=7). The median age at diagnosis was 57 (interquartile range [IQR], 49-66) years; 37 (49%) were women; and the median follow-up was 273 (IQR, 174-473) days. At diagnosis, the medium-sized panel detected 276 somatic variants in 35 genes (average 3.6 variants per patient) whereas the large panel detected 351 somatic variants in 74 genes (average 4.6 variants per patient). These variants were frequently detected in methylation and epigenetic genes (25%), signaling genes (20%) and transcription factors (12%). After treatment, MRD-negativity was indicated in 27 patients by the medium-sized panel versus 23 patients by the large panel; MRD-positivity was indicated in 49 patients by the medium-sized panel versus 53 patients by the large panel. Shorter overall survival was associated with MRD-positivity as determined by both panels: medium-sized panel (hazard ratio [HR], 3.00; 95% CI, 1.01-8.93; P<.05), large panel (HR, 3.41; 95% CI, 1.00-11.57; P<.05). Conclusion: A medium-sized NGS panel detected fewer somatic mutations than large NGS panel but both panels, when used as MRD markers, are similarly predictive of overall survival in AML patients. Citation Format: Yonghong Li, Jose Solis-Ruiz, Frederick K. Racke, Richard D. Press. Predicting survival outcomes in patients with acute myeloid leukemia: medium-sized versus large next-generation sequencing panels [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2204.
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关键词
acute myeloid leukemia,survival outcomes,medium-sized,next-generation
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