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Cancer Immunology Research
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Cancer Immunology Miniatures

In Human Visualization of Ibrutinib-Induced CLL Compartment Shift

Marius E. Mayerhoefer, Alexander Haug, Ulrich Jäger, Verena Pichler, Sarah Pfaff, Hans-Jürgen Wester, Marcus Hacker, Lukas Kazianka and Philipp B. Staber
Marius E. Mayerhoefer
1Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
2Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
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Alexander Haug
3Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
4Christian Doppler Laboratory for Applied Metabolomics, Medical University of Vienna, Vienna, Austria.
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  • ORCID record for Alexander Haug
Ulrich Jäger
5Division of Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
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Verena Pichler
3Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
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Sarah Pfaff
3Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
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Hans-Jürgen Wester
6Pharmaceutical Radiochemistry, Technical University of Munich, Garching, Germany.
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Marcus Hacker
3Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
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Lukas Kazianka
5Division of Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
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Philipp B. Staber
5Division of Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
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  • For correspondence: philipp.staber@meduniwien.ac.at
DOI: 10.1158/2326-6066.CIR-19-0880 Published August 2020
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Abstract

Bruton tyrosine kinase inhibitor ibrutinib is effective in treating chronic lymphocytic leukemia (CLL). However, after ibrutinib treatment initiation, patients frequently experience an increase of CLL blood cell count. This phenomenon in clinical practice is thought to reflect a “compartment shift” of CLL cells from lymph nodes to the peripheral blood, but the actual shifting has not yet been demonstrated. Using [68Ga]Pentixafor-PET/MRI for in vivo CXCR4 visualization, we here provide images of topical changes of CLL cells upon ibrutinib treatment. Within the first month of ibrutinib treatment, mean standardized [68Ga]Pentixafor uptake decreased in the bone marrow and lymph nodes, whereas [68Ga]Pentixafor uptake increased in the spleen. Leukocytosis rose, as did numbers of CXCR4high (tissue-resident) CLL cells. Volumes of lymph nodes and spleen decreased. Upon longer ibrutinib treatment, leukocytosis decreased, followed by a decrease of [68Ga]Pentixafor uptake in the spleen. These results support the preexisting clinical hypothesis of a “compartment shift” of CLL cells from the lymph nodes to the peripheral blood, but also refine the mechanistic model by describing early clearing of the bone marrow and redistribution of CLL cells to the orthotopic splenic cavernous system in response to ibrutinib treatment.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).

  • Cancer Immunol Res 2020;8:984–9

  • Received November 7, 2019.
  • Revision received March 18, 2020.
  • Accepted June 18, 2020.
  • Published first June 24, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Immunology Research: 8 (8)
August 2020
Volume 8, Issue 8
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In Human Visualization of Ibrutinib-Induced CLL Compartment Shift
Marius E. Mayerhoefer, Alexander Haug, Ulrich Jäger, Verena Pichler, Sarah Pfaff, Hans-Jürgen Wester, Marcus Hacker, Lukas Kazianka and Philipp B. Staber
Cancer Immunol Res August 1 2020 (8) (8) 984-989; DOI: 10.1158/2326-6066.CIR-19-0880

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In Human Visualization of Ibrutinib-Induced CLL Compartment Shift
Marius E. Mayerhoefer, Alexander Haug, Ulrich Jäger, Verena Pichler, Sarah Pfaff, Hans-Jürgen Wester, Marcus Hacker, Lukas Kazianka and Philipp B. Staber
Cancer Immunol Res August 1 2020 (8) (8) 984-989; DOI: 10.1158/2326-6066.CIR-19-0880
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