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A phase 1 dose-escalation study of low-dose lenalidomide maintenance post-allogeneic stem cell transplantation for high-risk acute myeloid leukaemia or myelodysplastic syndrome

Bone Marrow Transplantation (2024)Cite this article

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Relapse following allogeneic haematopoietic stem cell transplantation (alloSCT) remains the leading cause of treatment failure for high-risk (HR) acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) [1, 2]. Disease relapse frequently occurs early and is associated with a dismal prognosis [1,2,3,4]. With the rare exception of targeted therapies in certain AML subtypes, there are limited effective post-transplant strategies to prevent relapse.

Non-pharmacologic strategies have been utilised to reduce disease relapse by enhancing the graft-versus-leukaemia (GVL) effect [5]. However, approaches such as early immunosuppression withdrawal or donor lymphocyte infusions are counterbalanced by the risk of invoking graft-versus-host disease (GVHD). The immunomodulatory agent lenalidomide has the potential to promote the GVL effect by enhancing T- and NK-cell activation and increasing interleukin-2 and interferon-gamma production [6,7,8]. However, when utilised at a dose of 10 mg daily, post-transplant lenalidomide resulted in an unacceptably high incidence of acute GVHD [9, 10] therefore limiting its potential as a post-transplant maintenance agent.

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Fig. 1: Treatment timeline.

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The original contributions presented in the study were included in the article and Supplementary Information. Further inquiries can be directed to the corresponding author.

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Acknowledgements

The authors acknowledge the Melbourne Cytometry Platform for access to their flow cytometry instruments, and the Snowdome Foundation and Celgene Corporation, a Bristol-Myers Squibb Company, for sponsoring the study. Lenalidomide used in this study was supplied by Celgene Corporation.

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Authors and Affiliations

  1. ACRF Translational Research Laboratory, Royal Melbourne Hospital, Melbourne, VIC, Australia

    Ray Mun Koo, Eric Wong, Joanne E. Davis, Travis Perera, Andrew Lim, Rachel M. Koldej & David S. Ritchie

  2. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia

    Ray Mun Koo, Eric Wong, Joanne E. Davis, Andrew Lim, Rachel M. Koldej & David S. Ritchie

  3. Clinical Haematology, Peter MacCallum Cancer Centre–Royal Melbourne Hospital, Melbourne, VIC, Australia

    Ray Mun Koo, Travis Perera & David S. Ritchie

  4. Department of Clinical Haematology, Austin Health, Melbourne, VIC, Australia

    Eric Wong & Andrew Lim

  5. Wellington Blood and Cancer Centre, Wellington Hospital, Wellington, New Zealand

    Travis Perera

Authors
  1. Ray Mun Koo
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  2. Eric Wong
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  7. David S. Ritchie
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Contributions

DSR conceived, designed and supervised the trial and was involved in patient recruitment and data interpretation. RM Koo was responsible for patient recruitment, conducting the trial, collation and assembly of data, analysis and interpretation of data. EW was responsible for trial conception and design, patient recruitment, conducting the trial, collation and assembly of data, analysis and interpretation of data. JED was responsible for trial conception and design, collation and assembly of data, and data analysis and interpretation. TP was involved in trial conception and design, and patient recruitment. AL was involved in trial conception and design. RM Koldej was involved in trial conception, design and supervision, collation and assembly of data and data interpretation. All authors were involved in the manuscript writing and approval of the final manuscript.

Corresponding author

Correspondence to David S. Ritchie.

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The authors declare no competing interests.

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Koo, R.M., Wong, E., Davis, J.E. et al. A phase 1 dose-escalation study of low-dose lenalidomide maintenance post-allogeneic stem cell transplantation for high-risk acute myeloid leukaemia or myelodysplastic syndrome. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-023-02195-x

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