Measurable residual disease monitoring in AML with FLT3-ITD treated with intensive chemotherapy plus midostaurin
Year: 2024
Type: article
Abstract: 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.
Source: Blood Advances
Authors: Frank G. Rücker, Lars Bullinger, Sibylle Cocciardi, Sabrina Skambraks, Tamara J. Luck, Daniela Weber, Julia Krzykalla, Ema Pozek, Isabelle Schneider, Andrea Corbacioglu, Verena I. Gaidzik, Annika Meid, Sophia Aicher, Frank Stegelmann, Anika Schrade, Frauke Theis, Walter Fiedler, Helmut R. Salih, Gerald Wulf, Hans Salwender, Thomas Schroeder, Katharina S. Götze, Michael W. M. Kühn, Michael Lübbert, Richard F. Schlenk, Axel Benner, Felicitas Thol, Michael Heuser, Arnold Ganser, Hartmut Döhner, Konstanze Döhner
Institutions: University Hospital Ulm, Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin, Universität Ulm, German Cancer Research Center, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Universitätsklinikum Tübingen, University of Tübingen, Universitätsmedizin Göttingen, University of Göttingen, Asklepios Klinik Altona, Asklepios Klinik St. Georg, Asklepios, Düsseldorf University Hospital, Heinrich Heine University Düsseldorf, Technical University of Munich, Johannes Gutenberg University Mainz, University Medical Center of the Johannes Gutenberg University Mainz, University of Freiburg, University Medical Center Freiburg, Heidelberg University, University Hospital Heidelberg, National Center for Tumor Diseases, Medizinische Hochschule Hannover
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
Funders: 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
OpenAlex ID: W4402975432