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Maintenance sorafenib in FLT3-ITD AML following allogeneic HCT favorably impacts relapse and overall survival

Bone Marrow Transplantation volume 54, pages 1518–1520 (2019)Cite this article

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Internal tandem duplications in or near the juxtamembrane domain of the receptor tyrosine kinase fms-like tyrosine kinase 3 (FLT3-ITDs) are mutated in ~25% of adult acute myeloid leukemia (AML) cases, and is an independent risk factor for higher relapse risk and inferior survival [1], even after allogeneic hematopoietic cell transplantation (HCT) [2,3,4]. Recently, FLT3 tyrosine kinase inhibitors (TKIs) have demonstrated safety and efficacy in phase I/II studies of FLT3 mutated AML [5,6,7] and are being investigated as post-HCT maintenance therapy. Herein, we report the off-label use of TKI inhibitor (sorafenib) in the post-HCT setting and correlate it with clinical outcomes.

We conducted a retrospective study on 406 pediatric and adult AML patients undergoing first-time HCT between January 2008 and December 2017. This study was institutional review board (IRB) approved (HUM0123693). Data abstraction of patient, disease, and transplant-related variables was performed through manual chart review of the Electronic Medical Record supported by the Electronic Medical Record Search Engine (EMERSE) [3, 8].

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Acknowledgements

This work was supported by the A. Alfred Taubman Medical Research Institute and the Edith S. Briskin/Shirley K Schlafer Foundation (to SWC). We wish to thank the patients who participated in the University of Michigan Long-Term Evaluation of the Biology and Outcomes of Hematopoietic Stem Cell Transplantation and Cellular Therapy (HUM43287) protocol. This work was previously presented at the Relapse After HSCT Conference in Chicago, IL (October 2018). A travel stipend was awarded to GC.

Author contributions

GC: data curation, writing-original draft, writing-review/editing; MG: data curation, writing-review/editing; EG: data curation, visualization, writing-review/editing; TC: data curation, visualization, writing-review/editing; JB: data curation, writing-review/editing; DB: conceptualization; writing-review/editing; BM: writing-review/editing; AP: writing-review/editing; DF: writing-review/editing; PR: writing-review/editing; JM: writing-review/editing; SWC: conceptualization, data curation, investigation, methodology, formal analysis, resources, supervision, validation, visualization, writing-original draft, writing-review/editing.

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Author notes

  1. These authors contributed equally: Grant Chappell, Marcus Geer

Authors and Affiliations

  1. Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA

    Grant Chappell, Erin Gatza, Tracey Churay, Joseph Brisson & Sung Won Choi

  2. Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA

    Marcus Geer, Dale Bixby, Brian Parkin, Pavan Reddy & John Magenau

  3. Department of Statistics, University of Michigan School of Public Health, Ann Arbor, MI, USA

    Thomas Braun

  4. University of Michigan College of Pharmacy, Ann Arbor, MI, USA

    Bernard Marini, Anthony Perissinotti & David Frame

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  1. Grant Chappell
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Correspondence to Sung Won Choi.

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Chappell, G., Geer, M., Gatza, E. et al. Maintenance sorafenib in FLT3-ITD AML following allogeneic HCT favorably impacts relapse and overall survival. Bone Marrow Transplant 54, 1518–1520 (2019). https://doi.org/10.1038/s41409-019-0493-5

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