Abstract 2440: Single-cell MRD profiling identifies CXCR4-high AML as a responder population to CXCR4 inhibition with Motixafortide

Cancer Research, vol. 86, pp. 2440

Abstract

Abstract Background: The CXCL12-CXCR4 axis mediates bone marrow niche mediated protection of leukemic stem cells and contributes to chemoresistance. Motixafortide is a potent CXCR4 antagonist that disrupts leukemic cell retention in the microenvironment. We leveraged single-cell minimal residual disease (scMRD) profiling to quantify CXCR4 expression and clonal persistence after consolidation therapy within the BLAST trial (NCT02502968), aiming to define predictive biomarkers of Motixafortide response. Methods: Among 128 randomized AML patients in first complete remission (CR), 56 underwent bone marrow scMRD analysis using the Tapestri platform (Mission Bio) targeting 40 recurrent mutation hotspots and 19 surface markers including CXCR4. CXCR4 expression was quantified at single-cell resolution and dichotomized by cohort median. Clinical outcomes were correlated with treatment and scMRD metrics. Results: Although relapse-free survival (RFS) was not different between treatment arms in the ITT population (median RFS: 10.3 vs. 11.5 months, p=0.98), scMRD profiling uncovered a CXCR4 dependent treatment effect. In the placebo arm, high CXCR4 expression correlated with increased relapse risk (p=0.02). In contrast, in the Motixafortide arm, high CXCR4 expression was associated with reduced relapse (p=0.047). A multivariable Cox model confirmed a significant treatment by CXCR4 interaction (HRinteraction 0.032, 95% CI 0.004 to 0.269, p=0.0015), supporting CXCR4 as a predictive biomarker for Motixafortide benefit. scMRD revealed persistent clonal diversity, but conventional MRD positivity did not associate with outcome. Conclusion: While the BLAST trial showed no overall difference in RFS, single-cell MRD analysis revealed differential treatment effects according to CXCR4 expression. These findings suggest that CXCR4 may serve as a biomarker for response to Motixafortide and highlight the potential of single-cell profiling to inform patient stratification. Citation Format: Enise Ceran, Sonia Jaramillo-Segura, Anne Kahtrin Merbach, Christian Rohde, Robert Durruthy-Durruthy, Adam Sciambi, Marc Arribas-Layton, Michelle Lotze, Maxi Wass, Kathrin Rieger, Mathias Hänel, Regina Herbst, Christoph Röllig, Edgar Jost, Richard Schlenk, Katharina Götze, Marina Scheller, Marion Subklewe, Simone Kowoll, Jörg Steighardt, Bayram Edemir, Lutz P. Müller, Irit Glicko-Kabir, Abi Vainstein-Haras, Cora Gromann, Ella Sorani, Shaul Kadosh, Andreas Wienke, Claudia Baldus, Uwe Platzbecker, Hubert Serve, Martin Bornhäuser, Carsten Müller-Tidow. Single-cell MRD profiling identifies CXCR4-high AML as a responder population to CXCR4 inhibition with Motixafortide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2440.

Authors 32

1. Enise Ceran

   University Hospital Heidelberg

   Affiliation as printed

   1Heidelberg University Hospital, Heidelberg, Germany;

2. Sonia Jaramillo-Segura

   University Hospital Heidelberg

   Affiliation as printed

   1Heidelberg University Hospital, Heidelberg, Germany;

3. A. K. Merbach

   University Hospital Heidelberg

   Affiliation as printed

   1Heidelberg University Hospital, Heidelberg, Germany;

4. Christian Rohde

   University Hospital Heidelberg

   Affiliation as printed

   1Heidelberg University Hospital, Heidelberg, Germany;

5. Robert Durruthy-Durruthy

   Mission Bio (United States)

   Affiliation as printed

   2Mission Bio, San Francisco, CA;

6. Adam Sciambi

   Mission Bio (United States)

   Affiliation as printed

   2Mission Bio, San Francisco, CA;

7. Marc Arribas-Layton

   Mission Bio (United States)

   Affiliation as printed

   2Mission Bio, San Francisco, CA;

8. Michelle Lotze

   University Hospital Heidelberg

   Affiliation as printed

   1Heidelberg University Hospital, Heidelberg, Germany;

9. Maxi Wass

   Martin Luther University Halle-Wittenberg

   Affiliation as printed

   3Martin Luther University Halle-Wittenberg, Halle, Germany;

10. Kathrin Rieger

    Humboldt-Universität zu Berlin · Freie Universität Berlin

    Affiliation as printed

    4Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany;

11. Mathias Hänel

    Klinikum Chemnitz

    Affiliation as printed

    5Klinikum Chemnitz, Chemnitz, Germany;

12. Regina Herbst

    Klinikum Chemnitz

    Affiliation as printed

    5Klinikum Chemnitz, Chemnitz, Germany;

13. Christoph Röllig

    University Hospital Carl Gustav Carus

    Affiliation as printed

    6University Hospital Carl Gustav Carus, Dresden, Germany;

14. Edgar Jost Aachen 7Faculty of Medicine

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    7Faculty of Medicine University Hospital RWTH Aachen, Aachen, Germany;

15. Richard Schlenk

    University Hospital Heidelberg

    Affiliation as printed

    1Heidelberg University Hospital, Heidelberg, Germany;

16. Katharina S. S. Götze

    Technical University of Munich

    Affiliation as printed

    8Technical University Munich School of Medicine and Health, Munich, Germany;

17. Marina Scheller

    University Hospital Heidelberg

    Affiliation as printed

    1Heidelberg University Hospital, Heidelberg, Germany;

18. Marion S. Subklewe

    Ludwig-Maximilians-Universität München

    Affiliation as printed

    9University Hospital LMU Munich, Munich, Germany;

19. Simone Kowoll

    Martin Luther University Halle-Wittenberg

    Affiliation as printed

    10Martin-Luther University Halle-Wittenberg, Halle, Germany;

20. Jörg Steighardt

    Martin Luther University Halle-Wittenberg

    Affiliation as printed

    10Martin-Luther University Halle-Wittenberg, Halle, Germany;

21. Bayram Edemir

    Martin Luther University Halle-Wittenberg

    Affiliation as printed

    3Martin Luther University Halle-Wittenberg, Halle, Germany;

22. Lutz P. Müller

    Martin Luther University Halle-Wittenberg

    Affiliation as printed

    3Martin Luther University Halle-Wittenberg, Halle, Germany;

23. Irit Glicko‐Kabir

    BioLineRx Ltd. (Israel)

    Affiliation as printed

    11BiolineRx, Modi'in, Israel;

24. Abi Vainstein‐Haras

    BioLineRx Ltd. (Israel)

    Affiliation as printed

    11BiolineRx, Modi'in, Israel;

25. Cora Gromann

    Martin Luther University Halle-Wittenberg

    Affiliation as printed

    10Martin-Luther University Halle-Wittenberg, Halle, Germany;

26. Ella Sorani

    BioLineRx Ltd. (Israel)

    Affiliation as printed

    11BiolineRx, Modi'in, Israel;

27. Shaul E. Kadosh

    BioLineRx Ltd. (Israel)

    Affiliation as printed

    11BiolineRx, Modi'in, Israel;

28. Claudia D. Baldus

    University Hospital Schleswig-Holstein

    Affiliation as printed

    13University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;

29. Uwe Platzbecker

    University Hospital Leipzig · Leipzig University

    Affiliation as printed

    14Hemostaseology and Infectious Diseases, University Leipzig Medical Center, Leipzig, Germany;

30. Hubert L. Serve

    Goethe University Frankfurt · University Hospital Frankfurt

    Affiliation as printed

    15Goethe-University Frankfurt, University Hospital, Frankfurt am Main, Germany;

31. Martin Bornhäuser

    University Hospital Carl Gustav Carus

    Affiliation as printed

    16Carl Gustav Carus Univ. Hospital, Dresden, Germany

32. Carsten Müller‐Tidow

    University Hospital Heidelberg

    Affiliation as printed

    1Heidelberg University Hospital, Heidelberg, Germany;