Multi-target measurable residual disease assessed by error-corrected sequencing in patients with acute myeloid leukemia: An ALFA study. Hirsch, P., Lambert, J., Bucci, M., Deswarte, C., Boudry, A., Lambert, J., Fenwarth, L., Micol, J., Terré, C., Celli-Lebras, K., Thomas, X., Dombret, H., Duployez, N., Preudhomme, C., Itzykson, R., & Delhommeau, F. Blood Cancer Journal, 14(1):1–9, June, 2024. ![Multi-target measurable residual disease assessed by error-corrected sequencing in patients with acute myeloid leukemia: An ALFA study [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex The evaluation of measurable residual disease (MRD) in acute myeloid leukemia (AML) using comprehensive mutation analysis by next-generation sequencing (NGS) has been investigated in several studies. However controversial results exist regarding the detection of persisting mutations in DNMT3A, TET2, and ASXL1 (DTA). Benchmarking of NGS-MRD taking into account other molecular MRD strategies has to be done. Here, we performed error-corrected-NGS-MRD in 189 patients homogeneously treated in the ALFA-0702 study (NCT00932412). Persistence of non-DTA mutations (HR = 2.23 for RFS and 2.26 for OS), and DTA mutations (HR = 2.16 for OS) were associated with poorer prognosis in multivariate analysis. Persistence of at least two mutations in complete remission (CR) was associated with a higher cumulative incidence of relapse (CIR) (HR = 3.71, p \textless 0.0001), lower RFS (HR = 3.36, p \textless 0.0001) and OS (HR = 3.81, p = 0.00023) whereas persistence of only one mutation was not. In 100 analyzable patients, WT1-MRD, but not NGS-MRD, was an independent factor for RFS and OS. In the subset of 67 NPM1 mutated patients, both NPM1 mutation detection (p = 0.0059) and NGS-MRD (p = 0.035) status were associated with CIR. We conclude that detectable NGS-MRD including DTA mutations correlates with unfavorable prognosis in AML. Its integration with alternative MRD strategies in AML management warrants further investigations.
@article{hirsch_multi-target_2024,
title = {Multi-target measurable residual disease assessed by error-corrected sequencing in patients with acute myeloid leukemia: {An} {ALFA} study},
volume = {14},
copyright = {2024 The Author(s)},
issn = {2044-5385},
shorttitle = {Multi-target measurable residual disease assessed by error-corrected sequencing in patients with acute myeloid leukemia},
url = {https://www.nature.com/articles/s41408-024-01078-8},
doi = {10.1038/s41408-024-01078-8},
abstract = {The evaluation of measurable residual disease (MRD) in acute myeloid leukemia (AML) using comprehensive mutation analysis by next-generation sequencing (NGS) has been investigated in several studies. However controversial results exist regarding the detection of persisting mutations in DNMT3A, TET2, and ASXL1 (DTA). Benchmarking of NGS-MRD taking into account other molecular MRD strategies has to be done. Here, we performed error-corrected-NGS-MRD in 189 patients homogeneously treated in the ALFA-0702 study (NCT00932412). Persistence of non-DTA mutations (HR = 2.23 for RFS and 2.26 for OS), and DTA mutations (HR = 2.16 for OS) were associated with poorer prognosis in multivariate analysis. Persistence of at least two mutations in complete remission (CR) was associated with a higher cumulative incidence of relapse (CIR) (HR = 3.71, p {\textless} 0.0001), lower RFS (HR = 3.36, p {\textless} 0.0001) and OS (HR = 3.81, p = 0.00023) whereas persistence of only one mutation was not. In 100 analyzable patients, WT1-MRD, but not NGS-MRD, was an independent factor for RFS and OS. In the subset of 67 NPM1 mutated patients, both NPM1 mutation detection (p = 0.0059) and NGS-MRD (p = 0.035) status were associated with CIR. We conclude that detectable NGS-MRD including DTA mutations correlates with unfavorable prognosis in AML. Its integration with alternative MRD strategies in AML management warrants further investigations.},
language = {en},
number = {1},
urldate = {2024-06-18},
journal = {Blood Cancer Journal},
author = {Hirsch, Pierre and Lambert, Jérôme and Bucci, Maxime and Deswarte, Caroline and Boudry, Augustin and Lambert, Juliette and Fenwarth, Laurene and Micol, Jean-Baptiste and Terré, Christine and Celli-Lebras, Karine and Thomas, Xavier and Dombret, Hervé and Duployez, Nicolas and Preudhomme, Claude and Itzykson, Raphael and Delhommeau, Francois},
month = jun,
year = {2024},
keywords = {Acute myeloid leukaemia, Cancer genetics, Customer myeloid solution, DDM},
pages = {1--9},
}
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However controversial results exist regarding the detection of persisting mutations in DNMT3A, TET2, and ASXL1 (DTA). Benchmarking of NGS-MRD taking into account other molecular MRD strategies has to be done. Here, we performed error-corrected-NGS-MRD in 189 patients homogeneously treated in the ALFA-0702 study (NCT00932412). Persistence of non-DTA mutations (HR = 2.23 for RFS and 2.26 for OS), and DTA mutations (HR = 2.16 for OS) were associated with poorer prognosis in multivariate analysis. Persistence of at least two mutations in complete remission (CR) was associated with a higher cumulative incidence of relapse (CIR) (HR = 3.71, p \\textless 0.0001), lower RFS (HR = 3.36, p \\textless 0.0001) and OS (HR = 3.81, p = 0.00023) whereas persistence of only one mutation was not. In 100 analyzable patients, WT1-MRD, but not NGS-MRD, was an independent factor for RFS and OS. In the subset of 67 NPM1 mutated patients, both NPM1 mutation detection (p = 0.0059) and NGS-MRD (p = 0.035) status were associated with CIR. We conclude that detectable NGS-MRD including DTA mutations correlates with unfavorable prognosis in AML. 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