Inhibition of high CXCR4 with motixafortide and absence of single-cell MRD predict outcome after AML consolidation
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: ABSTRACT: Relapse after remission remains the primary cause of treatment failure in acute myeloid leukemia (AML), underscoring the need for strategies to eliminate residual leukemic cells. The bone marrow (BM) microenvironment, largely orchestrated by the CXC chemokine receptor 4 (CXCR4)-CXC motif chemokine 12 axis (CXCL12), enables leukemia cell survival and chemoresistance by anchoring blasts in their protective BM niche. Motixafortide, a selective CXCR4 antagonist, mobilizes leukemic cells and disrupts tumor microenvironment interactions in preclinical models. In this randomized, double-blind, placebo-controlled phase 2 trial, 128 patients in first remission received high-dose cytarabine plus motixafortide or placebo. Median relapse-free survival did not substantially differ between groups: 10.3 months (95% confidence interval [CI], 8.0-12.0) for motixafortide and 11.5 months (95% CI, 8.6-24.1) for placebo (log-rank P = .98). But single-cell measurable residual disease (scMRD) analysis, performed before consolidation, demonstrated heterogeneity of CXCR4 inhibition benefit; in the placebo group, higher CXCR4 expression was associated with increased relapse risk (P = .02), whereas in the motixafortide group, higher CXCR4 expression was linked to a reduced relapse rate (P = .047). Exploratory analyses identified scMRD levels at which higher MRD burden was associated with inferior overall survival. Taken together, combining functional MRD profiling with biomarker-driven patient selection, such as CXCR4 expression, may enable more precise and effective postremission interventions in AML. This trial was registered at www.clinicaltrials.gov as NCT02502968 and at EudraCT as 2014-002702-21.
Source: Blood
Authors: Enise Ceran, Sonia Jaramillo Segura, Anne Kathrin Merbach, Christian Rohde, Maxi Wass, Judith Schaffrath, Robert Durruthy-Durruthy, Marc Arribas-Layton, Adam Sciambi, Kathrin Rieger, Axel Nogai, Mathias Hänel, Regina Herbst, Friedrich Stölzel, Christoph Röllig, Edgar Jost, Richard F. Schlenk, Michelle Lotze, Richard Noppeney, Christian Brandts, Utz Krug, Katharina S. Götze, Sebastian Buske, Axel Florschütz, Jörg Schubert, Bernhard Opitz, Eva Eßeling, Stephan von Witzendorff, Marion Subklewe, Martin Kaufmann, Norbert Frickhofen, Christian W. Scholz, Kerstin Schäfer-Eckart, Volker Kunzmann, Martin Schmidt-Hieber, Herbert Sayer, Andreas Rank, Philipp Hemmati, Frank Schüler, Marina Scheller, Simone Kowoll, Jörg Steighardt, Bayram Edemir, Beatrice Ludwig-Kraus, Lutz P. Müller, Sabine Edemir, Abi Vainstein-Haras, Ella Sorani, Irit Glicko-Kabir, Shaul Kadosh, Sigal Tavor, Cora Gromann, Andreas Wienke, Marcus Bauer, Claudia Wickenhauser, Claudia D. Baldus, Uwe Platzbecker, Adelheid Cerwenka, Hubert Serve, Martin Bornhäuser, Christian Junghanß, Carsten Müller-Tidow
Institutions: Heidelberg University, University Hospital Heidelberg, National Center for Tumor Diseases, Martin Luther University Halle-Wittenberg, Mission Bio (United States), Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin, Klinikum Chemnitz, University Hospital Schleswig-Holstein, University Hospital Carl Gustav Carus, Technische Universität Dresden, Universitätsklinikum Aachen, RWTH Aachen University, Krankenhaus der Barmherzigen Brüder Trier, Goethe University Frankfurt, University Hospital Frankfurt, Technical University of Munich, Städtisches Klinikum Dessau, Elblandklinikum Riesa, Krankenhaus St. Elisabeth und St. Barbara, University Hospital Münster, Gemeinschaftsklinikum Mittelrhein, Ludwig-Maximilians-Universität München, Robert Bosch Hospital, Helios Dr. Horst Schmidt Kliniken Wiesbaden, Vivantes Klinikum, Nuremberg Hospital, Paracelsus Medizinische Privatuniversität, University of Würzburg, Comprehensive Cancer Center Mainfranken, Universitätsklinikum Würzburg, Medizinische Universität Lausitz - Carl Thiem, Helios Klinikum Erfurt, University Hospital Augsburg, Klinikum Ernst von Bergmann, University Hospital in Halle, BioLineRx Ltd. (Israel), Assuta Medical Center, University Hospital Leipzig, Medizinische Fakultät Mannheim, Universitätsmedizin Rostock, University of Rostock
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,500
OpenAlex ID: W7154366176