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Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties

Bone Marrow Transplantation volume 54, pages 44–52 (2019)Cite this article

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Abstract

The aim of this retrospective study was to investigate the safety and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) in patients pre-treated with ibrutinib. Eligible were patients aged >18 years allotransplanted for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) after prior exposure to ibrutinib who were registered with the EBMT registry. Seventy patients (CLL 48, MCL 22) were included. At the time of alloHCT, 73% of the patients were ibrutinib responsive. All patients except one engrafted, and acute GVHD grade 2–4 (3–4) was observed in 49% (12%) of 68 evaluable patients. The cumulative incidence of chronic GVHD was 54% 1 year after transplant. In the CLL group, 12-month non-relapse mortality, relapse incidence (RI), progression-free survival (PFS), and overall survival (OS) were 10, 30, 60, and 72%, respectively, and in the MCL group 5, 19, 76, and 86%, respectively. Pre-transplant ibrutinib failure and poor performance status predicted inferior RI, PFS and OS in the CLL group. In conclusion, ibrutinib does not affect the safety of a subsequent alloHCT. While the relatively high post-transplant relapse risk in ibrutinib-exposed patients with CLL deserves further study, in patients with MCL consolidating disease responses to ibrutinib with alloHCT seems to be a promising option.

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Acknowledgements

The authors acknowledge all collaborating EBMT Investigators and Institutions that contributed cases to this study.

Author contributions

PD and MM: designed and performed research, analyzed data, and wrote the paper; SD: performed research, analyzed data; AB: designed and performed research, analyzed data; PB, MS, AN, CS, JC, DN, LM, EV, IS, HS, NA, JF, DR, PL, JP, MvG, ND, HL-W, TB, GW, WB, DB, SS, MC, MS, and CPF performed research; NK, SM, and JS designed and performed research.

Author information

Author notes

  1. These authors contributed equally: Peter Dreger, Mauricette Michallet.

Authors and Affiliations

  1. EBMT Chronic Malignancies Working Party, Leiden, Netherlands

    Peter Dreger, Paul Bosman, Michel van Gelder, Nicolaus Kröger & Johannes Schetelig

  2. EBMT Lymphoma Working Party, Paris, France

    Peter Dreger, Sascha Dietrich, Ariane Boumendil & Silvia Montoto

  3. Department of Medicine V, University of Heidelberg, Heidelberg, Germany

    Peter Dreger & Sascha Dietrich

  4. Service d’Hématologie, Centre Léon Bérard, Lyon, France

    Mauricette Michallet & Mohamad Sobh

  5. Hematology Division, Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel

    Arnon Nagler

  6. University of Cologne, Cologne, Germany

    Christof Scheid

  7. Department of Hematology, Erasmus MC Cancer Center, Rotterdam, The Netherlands

    Jan Cornelissen

  8. Department of Hematology and Medical Oncology, University Hospital, Leipzig, Germany

    Dietger Niederwieser

  9. Martin-Luther-Universität Halle-Wittenberg, Halle, Germany

    Lutz Müller

  10. Hope Directorate St. James Hospital, Dublin, Ireland

    Elizabeth Vandenberghe

  11. Department of Haematology, Ospedali Riuniti Ancona, Ancona, Italy

    Ilaria Scortechini

  12. Department of Hematology, University Hospital Leuven and KU Leuven, Leuven, Belgium

    Helene Schoemans

  13. Rigshospitalet, Copenhagen, Denmark

    Niels S. Andersen

  14. Department of Medicine I, University of Freiburg, Freiburg, Germany

    Jürgen Finke

  15. Unit of Blood Diseases and Bone Marrow Transplantation, ASST Spedali Civili, Chair of Hematology, University of Brescia, Brescia, Italy

    Domenico Russo

  16. Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden

    Per Ljungman

  17. University Hospital, Basel, Switzerland

    Jakob Passweg

  18. Department of Internal Medicine, Hematology Division, Maastricht University Medical Center, Maastricht, The Netherlands

    Michel van Gelder

  19. University Hospital Center Rebro, Zagreb, Croatia

    Nadira Durakovic

  20. Centre Hospitalier Lyon Sud, Lyon, France

    Helene Labussiere-Wallet

  21. Department of Medicine II, Goethe University, Frankfurt, Germany

    Tobias Berg

  22. Universitätsklinikum Göttingen, Göttingen, Germany

    Gerald Wulf

  23. Department of Hematology & Oncology, Medical Center, University Hospital Tuebingen, Tuebingen, Germany

    Wolfgang Bethge

  24. Department of Medicine III, University Hospital Ulm, Ulm, Germany

    Donald Bunjes & Stefan Stilgenbauer

  25. Az. Ospedaliera S. Croce e Carle, Cuneo, Italy

    Maria Elisa Canepari

  26. Department of Hematology, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands

    Michel Schaap

  27. Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, UK

    Christopher P. Fox

  28. University Hospital Eppendorf, Hamburg, Germany

    Nicolaus Kröger

  29. Department of Haemato-oncology, St Bartholomew’s hospital, Barts Health NHS Trust, London, UK

    Silvia Montoto

  30. Universitätsklinikum Dresden, Dresden, Germany

    Johannes Schetelig

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  1. Peter Dreger
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Correspondence to Peter Dreger.

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Conflict of interest

PD: Consultancy for AbbVie, Roche and Janssen; consultancy and speakers bureau for Gilead; speakers bureau for Kite Pharma. MM: Consultancy and Speakers bureau for Sanofi, MSD, Octapharma, Pfizer, MAATPharma, Novartis. CPF: Consultancy, speakers bureau and travel grants from Janssen. MvG: Consultancy for Gilead and Janssen; speakers bureau for Abbvie, Gilead, Janssen and Roche; Educational support from Gilead. TB: Consultancy for Riemser; travel grants from Astellas, Alexion, Celgene, Abbvie. SS: Consultancy, Speakers bureau, travel grants and research funding from AbbVie, Amgen, Celgene, Gilead, GSK, Roche, Janssen, Novartis, Pharmacyclics. SM: Speakers bureau for Roche; travel grant from Gilead. JS: Consultancy and Speakers bureau for AbbVie, Gilead, Janssen, Roche, Sanofi; research funding from Genzyme, Sanofi, GSK, Novartis, Abbvie. The remaining authors declare that they have no conflict of interest.

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Dreger, P., Michallet, M., Bosman, P. et al. Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties. Bone Marrow Transplant 54, 44–52 (2019). https://doi.org/10.1038/s41409-018-0207-4

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