NGS-defined measurable residual disease (MRD) after initial chemotherapy as a prognostic biomarker for acute myeloid leukemia
Abstract Treated AML patients often have measurable residual disease (MRD) due to persisting low-level clones. This study assessed whether residual post-treatment somatic mutations, detected by NGS, were significantly prognostic for subsequent clinical outcomes. AML patients (n = 128) underwent both...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-04-01
|
| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-023-00833-7 |
| _version_ | 1797836627934969856 |
|---|---|
| author | Yonghong Li Jose Solis-Ruiz Fei Yang Nicola Long Carmen H. Tong Felicitas L. Lacbawan Frederick K. Racke Richard D. Press |
| author_facet | Yonghong Li Jose Solis-Ruiz Fei Yang Nicola Long Carmen H. Tong Felicitas L. Lacbawan Frederick K. Racke Richard D. Press |
| author_sort | Yonghong Li |
| collection | DOAJ |
| description | Abstract Treated AML patients often have measurable residual disease (MRD) due to persisting low-level clones. This study assessed whether residual post-treatment somatic mutations, detected by NGS, were significantly prognostic for subsequent clinical outcomes. AML patients (n = 128) underwent both pre-and post-treatment testing with the same 42-gene MRD-validated NGS assay. After induction, 59 (46%) patients were mutation-negative (0.0024 VAF detection limit) and 69 (54%) had ≥1 persisting NGS-detectable mutation. Compared with NGS-negative patients, NGS-positive patients had shorter overall survival (17 months versus median not reached; P = 0.004; hazard ratio = 2.2 [95% CI: 1.3–3.7]) and a shorter time to relapse (14 months versus median not reached; P = 0.014; HR = 1.9 [95% CI: 1.1–3.1]). Among 95 patients with a complete morphologic remission (CR), 43 (45%) were MRD-positive by NGS and 52 (55%) were MRD-negative. These MRD-positive CR patients had a shorter overall survival (16.8 months versus median not reached; P = 0.013; HR = 2.1 [95% CI: 1.2–3.9]) than did the MRD-negative CR patients. Post-treatment persisting MRD positivity, defined by the same NGS-based test used at diagnosis, is thus a more sensitive biomarker for low-level leukemic clones compared to traditional non-molecular methods and is prognostic of subsequent relapse and death. |
| first_indexed | 2024-04-09T15:11:59Z |
| format | Article |
| id | doaj.art-939cb0f1782d47228774cf7d70a357d2 |
| institution | Directory Open Access Journal |
| issn | 2044-5385 |
| language | English |
| last_indexed | 2024-04-09T15:11:59Z |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj.art-939cb0f1782d47228774cf7d70a357d22023-04-30T11:07:56ZengNature Publishing GroupBlood Cancer Journal2044-53852023-04-011311910.1038/s41408-023-00833-7NGS-defined measurable residual disease (MRD) after initial chemotherapy as a prognostic biomarker for acute myeloid leukemiaYonghong Li0Jose Solis-Ruiz1Fei Yang2Nicola Long3Carmen H. Tong4Felicitas L. Lacbawan5Frederick K. Racke6Richard D. Press7Quest DiagnosticsDepartment of Pathology, Oregon Health & Science UniversityDepartment of Pathology, Oregon Health & Science UniversityKnight Cancer Institute, Oregon Health & Science UniversityQuest DiagnosticsQuest DiagnosticsQuest DiagnosticsDepartment of Pathology, Oregon Health & Science UniversityAbstract Treated AML patients often have measurable residual disease (MRD) due to persisting low-level clones. This study assessed whether residual post-treatment somatic mutations, detected by NGS, were significantly prognostic for subsequent clinical outcomes. AML patients (n = 128) underwent both pre-and post-treatment testing with the same 42-gene MRD-validated NGS assay. After induction, 59 (46%) patients were mutation-negative (0.0024 VAF detection limit) and 69 (54%) had ≥1 persisting NGS-detectable mutation. Compared with NGS-negative patients, NGS-positive patients had shorter overall survival (17 months versus median not reached; P = 0.004; hazard ratio = 2.2 [95% CI: 1.3–3.7]) and a shorter time to relapse (14 months versus median not reached; P = 0.014; HR = 1.9 [95% CI: 1.1–3.1]). Among 95 patients with a complete morphologic remission (CR), 43 (45%) were MRD-positive by NGS and 52 (55%) were MRD-negative. These MRD-positive CR patients had a shorter overall survival (16.8 months versus median not reached; P = 0.013; HR = 2.1 [95% CI: 1.2–3.9]) than did the MRD-negative CR patients. Post-treatment persisting MRD positivity, defined by the same NGS-based test used at diagnosis, is thus a more sensitive biomarker for low-level leukemic clones compared to traditional non-molecular methods and is prognostic of subsequent relapse and death.https://doi.org/10.1038/s41408-023-00833-7 |
| spellingShingle | Yonghong Li Jose Solis-Ruiz Fei Yang Nicola Long Carmen H. Tong Felicitas L. Lacbawan Frederick K. Racke Richard D. Press NGS-defined measurable residual disease (MRD) after initial chemotherapy as a prognostic biomarker for acute myeloid leukemia Blood Cancer Journal |
| title | NGS-defined measurable residual disease (MRD) after initial chemotherapy as a prognostic biomarker for acute myeloid leukemia |
| title_full | NGS-defined measurable residual disease (MRD) after initial chemotherapy as a prognostic biomarker for acute myeloid leukemia |
| title_fullStr | NGS-defined measurable residual disease (MRD) after initial chemotherapy as a prognostic biomarker for acute myeloid leukemia |
| title_full_unstemmed | NGS-defined measurable residual disease (MRD) after initial chemotherapy as a prognostic biomarker for acute myeloid leukemia |
| title_short | NGS-defined measurable residual disease (MRD) after initial chemotherapy as a prognostic biomarker for acute myeloid leukemia |
| title_sort | ngs defined measurable residual disease mrd after initial chemotherapy as a prognostic biomarker for acute myeloid leukemia |
| url | https://doi.org/10.1038/s41408-023-00833-7 |
| work_keys_str_mv | AT yonghongli ngsdefinedmeasurableresidualdiseasemrdafterinitialchemotherapyasaprognosticbiomarkerforacutemyeloidleukemia AT josesolisruiz ngsdefinedmeasurableresidualdiseasemrdafterinitialchemotherapyasaprognosticbiomarkerforacutemyeloidleukemia AT feiyang ngsdefinedmeasurableresidualdiseasemrdafterinitialchemotherapyasaprognosticbiomarkerforacutemyeloidleukemia AT nicolalong ngsdefinedmeasurableresidualdiseasemrdafterinitialchemotherapyasaprognosticbiomarkerforacutemyeloidleukemia AT carmenhtong ngsdefinedmeasurableresidualdiseasemrdafterinitialchemotherapyasaprognosticbiomarkerforacutemyeloidleukemia AT felicitasllacbawan ngsdefinedmeasurableresidualdiseasemrdafterinitialchemotherapyasaprognosticbiomarkerforacutemyeloidleukemia AT frederickkracke ngsdefinedmeasurableresidualdiseasemrdafterinitialchemotherapyasaprognosticbiomarkerforacutemyeloidleukemia AT richarddpress ngsdefinedmeasurableresidualdiseasemrdafterinitialchemotherapyasaprognosticbiomarkerforacutemyeloidleukemia |