Measurable residual disease monitoring in AML with <i>FLT3</i>-ITD treated with intensive chemotherapy plus midostaurin

Measurable residual disease (MRD) monitoring in acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITDpos) has been hampered by the broad heterogeneity of ITD mutations. Using our recently developed FLT3-ITD paired-end next-generation sequencing (NGS)-based MRD assay (limit of detection 10-4 to 10-5), we evaluated the prognostic impact of MRD at different time points in 157 patients with FLT3-ITDpos AML who were enrolled in the German-Austrian Acute Myeloid Leukemia Study Group 16-10 trial and who were treated with a combination of intensive chemotherapy and midostaurin, followed by midostaurin maintenance. MRD negativity (MRDneg) after 2 cycles of chemotherapy (Cy2), which was observed in 111 of 142 (78%) patients, was predictive of superior 4-year rates of cumulative incidence of relapse (CIR) (4y-CIR; 26% vs 46%; P = .001) and overall survival (OS) (4y-OS; 70% vs 44%; P = .012). This survival advantage was also seen among patients who underwent allogeneic hematopoietic-cell transplantation during first complete remission (4y-CIR, 14% vs 39%; P = .001; 4y-OS, 71% vs 49%; P = .029). Multivariate models for CIR and OS after Cy2 revealed FLT3-ITD MRDneg as the only consistent favorable variable for CIR (hazard ratio [HR], 0.29; P = .006) and OS (HR, 0.39; P = .018). During follow-up, conversion from MRDneg to MRD positivity (MRDpos) was a strong, independent factor for inferior CIR (HR, 16.64; P < .001) and OS (HR, 4.05; P < .001). NGS-based FLT3-ITD MRD monitoring identifies patients at high risk for relapse and death following treatment with intensive chemotherapy and midostaurin. Using NGS-based technology.

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Publication Details

Journal
Blood Advances
Published
2024-09-30
DOI
https://doi.org/10.1182/bloodadvances.2024013758
Citations
11
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
5.00

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article

Measurable residual disease monitoring in AML with FLT3-ITD treated with intensive chemotherapy plus midostaurin

Tamara J. Luck, Frank Stegelmann, Arnold Ganser, Annika Meid et al.
11 citations
Blood Advances
Acute Myeloid Leukemia Research
5.00
article

Measurable residual disease monitoring in AML with FLT3-ITD treated with intensive chemotherapy plus midostaurin

Tamara J. Luck, Frank Stegelmann, Arnold Ganser, Annika Meid, Helmut R. Salih, Sabrina Skambraks, Gerald Wulf, Axel Benner, Lars Bullinger, Frauke Theis, Michael Lübbert, Isabelle Schneider, Michael Heuser, Richard F. Schlenk, Konstanze Döhner, Felicitas Thol, Frank G. Rücker, Sibylle Cocciardi, Katharina S. S. Götze, Hans Salwender, Thomas A. Schroeder, Daniela Weber, Verena I. Gaidzik, Anika Schrade, Walter Fiedler, Julia Krzykalla, Hartmut Döhner, Ema Požek, Michael W.M. Kühn, Andrea Corbacioglu, Sophia Aicher
article en
11 citations

Abstract

Measurable residual disease (MRD) monitoring in acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITDpos) has been hampered by the broad heterogeneity of ITD mutations. Using our recently developed FLT3-ITD paired-end next-generation sequencing (NGS)-based MRD assay (limit of detection 10-4 to 10-5), we evaluated the prognostic impact of MRD at different time points in 157 patients with FLT3-ITDpos AML who were enrolled in the German-Austrian Acute Myeloid Leukemia Study Group 16-10 trial and who were treated with a combination of intensive chemotherapy and midostaurin, followed by midostaurin maintenance. MRD negativity (MRDneg) after 2 cycles of chemotherapy (Cy2), which was observed in 111 of 142 (78%) patients, was predictive of superior 4-year rates of cumulative incidence of relapse (CIR) (4y-CIR; 26% vs 46%; P = .001) and overall survival (OS) (4y-OS; 70% vs 44%; P = .012). This survival advantage was also seen among patients who underwent allogeneic hematopoietic-cell transplantation during first complete remission (4y-CIR, 14% vs 39%; P = .001; 4y-OS, 71% vs 49%; P = .029). Multivariate models for CIR and OS after Cy2 revealed FLT3-ITD MRDneg as the only consistent favorable variable for CIR (hazard ratio [HR], 0.29; P = .006) and OS (HR, 0.39; P = .018). During follow-up, conversion from MRDneg to MRD positivity (MRDpos) was a strong, independent factor for inferior CIR (HR, 16.64; P < .001) and OS (HR, 4.05; P < .001). NGS-based FLT3-ITD MRD monitoring identifies patients at high risk for relapse and death following treatment with intensive chemotherapy and midostaurin. Using NGS-based technology.

Blood AdvancesVol. 8(23)
Universität Hamburg (DE), University of Freiburg (DE), German Cancer Research Center (DE), Universität Ulm (DE), Johannes Gutenberg University Mainz (DE), Heidelberg University (DE), University Medical Center Freiburg (DE), University Hospital Heidelberg (DE), Medizinische Hochschule Hannover (DE), Humboldt-Universität zu Berlin (DE), Asklepios Klinik Altona (DE), Düsseldorf University Hospital (DE), University Medical Center of the Johannes Gutenberg University Mainz (DE), University Medical Center Hamburg-Eppendorf (DE), National Center for Tumor Diseases (DE), Universitätsmedizin Göttingen (DE), Asklepios Klinik St. Georg (DE), University Cancer Center Hamburg (DE), University Hospital Ulm (DE), Heinrich Heine University Düsseldorf (DE), Technical University of Munich (DE), University of Göttingen (DE), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE), University of Tübingen (DE)
Amgen, Bristol-Myers Squibb, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Gilead Sciences, Celgene, Jazz Pharmaceuticals, Astex Pharmaceuticals, Agios Pharmaceuticals, Incyte, Syndax Pharmaceuticals, Astellas Pharma, Servier, Swedish Orphan Biovitrum, PharmaMar, MorphoSys, AOP Orphan, Loxo Oncology, Daiichi Sankyo Europe
Good health and well-being
Openalex Percentile: Top 4%
Acute Myeloid Leukemia Research
5.00
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