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.

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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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.

Corresponding author

Correspondence to Peter Dreger.

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DOI

https://doi.org/10.1038/s41409-018-0207-4

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