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Lymphoma

A novel lymphoma-associated macrophage interaction signature (LAMIS) provides robust risk prognostication in diffuse large B-cell lymphoma clinical trial cohorts of the DSHNHL

Leukemia volume 34, pages 543–552 (2020)Cite this article

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Abstract

Diffuse large B-cell lymphoma (DLBCL) is a disease with heterogeneous outcome. Stromal signatures have been correlated to survival in DLBCL. Their use, however, is hampered by the lack of assays for formalin-fixed paraffin-embedded material (FFPE). We constructed a lymphoma-associated macrophage interaction signature (LAMIS) interrogating features of the microenvironment using a NanoString assay applicable to FFPE. The clinical impact of the signature could be validated in a cohort of 466 patients enrolled in prospective clinical trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Patients with high expression of the signature (LAMIShigh) had shorter EFS, PFS, and OS. Multivariate analyses revealed independence from IPI factors in EFS (HR 1.7, 95% CI 1.2–2.4, p-value = 0.001), PFS (HR 1.8, 95% CI 1.2–2.5, p-value = 0.001) and OS (HR 1.8, 95% CI 1.3–2.7, p-value = 0.001). Multivariate analyses adjusted for the IPI factors showed the signature to be independent from COO, MYC rearrangements and double expresser status (DE). LAMIShigh and simultaneous DE status characterized a patient subgroup with dismal prognosis and early relapse. Our data underline the importance of the microenvironment in prognosis. Combined analysis of stromal features, the IPI and DE may provide a new rationale for targeted therapy.

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Acknowledgements

We thank Thomas Hees, Katja Bräutigam, and Daniela Pumm (Stuttgart), Theodora Nedeva (Würzburg), and Beate Mann and Katja Rillich (Leipzig) for excellent technical assistance.

Author information

Author notes

  1. These authors contributed equally: Annette M. Staiger, Michael Altenbuchinger, Marita Ziepert.

  2. Deceased: Michael Pfreundschuh.

Authors and Affiliations

  1. Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany

    Annette M. Staiger, Katrin S. Hüttl & German Ott

  2. Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, University of Tuebingen, Stuttgart, Germany

    Annette M. Staiger & Heike Horn

  3. Statistical Bioinformatics, Institute of Functional Genomics, University of Regensburg, Regensburg, Germany

    Michael Altenbuchinger, Christian Kohler, Michael Huttner, Gunther Glehr, Rainer Spang & Rainer Spang

  4. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany

    Marita Ziepert, Markus Loeffler, Markus Loeffler & Markus Loeffler

  5. Institute of Pathology, Hematopathology Section and Lymph Node Registry, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Wolfram Klapper, Monika Szczepanowski, Julia Richter & Wolfram Klapper

  6. Department of Internal Medicine II, Hematology Laboratory, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Monika Szczepanowski

  7. Pathodiagnostik Berlin, Berlin, Germany

    Harald Stein

  8. Haematopathologie Luebeck, Luebeck, Germany

    Alfred C. Feller

  9. Institute of Pathology, Universitätsklinikum Ulm, Ulm, Germany

    Peter Möller

  10. Dr. Senckenberg Institute of Pathology, Goethe University Hospital, Frankfurt, Germany

    Martin-Leo Hansmann

  11. DSHNHL Studiensekretariat, Universitätsklinikum des Saarlandes, Homburg, Germany

    Viola Poeschel & Gerhard Held

  12. Department of Medicine A, University Hospital Muenster, Muenster, Germany

    Norbert Schmitz & Norbert Schmitz

  13. Department of Hematology and Oncology, Georg-August Universität, Göttingen, Germany

    Lorenz Trümper, Lorenz Trümper & Lorenz Trümper

  14. Department of Internal Medicine III, Universitätsklinikum Regensburg, Regensburg, Germany

    Tobias Pukrop

  15. Institute of Pathology, Universität Würzburg and Comprehensive Cancer Center Mainfranken (CCCMF), Würzburg, Germany

    Andreas Rosenwald

  16. Institute of Human Genetics, University Ulm and University of Ulm Medical Center, Ulm, Germany

    Reiner Siebert

  17. Medizinische Klinik I, Saarland University Medical School, Homburg/Saar, Germany

    Michael Pfreundschuh

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  1. Annette M. Staiger
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the Emed Demonstrator Project

  • Markus Loeffler
  • , Reiner Siebert
  • , Wolfram Klapper
  • , Rainer Spang
  •  & Lorenz Trümper

German High Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL)

  • Michael Pfreundschuh
  • , Norbert Schmitz
  • , Lorenz Trümper
  •  & Markus Loeffler

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Staiger, A.M., Altenbuchinger, M., Ziepert, M. et al. A novel lymphoma-associated macrophage interaction signature (LAMIS) provides robust risk prognostication in diffuse large B-cell lymphoma clinical trial cohorts of the DSHNHL. Leukemia 34, 543–552 (2020). https://doi.org/10.1038/s41375-019-0573-y

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