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Graft-versus-host Disease

Salvage therapy with everolimus reduces the severity of treatment-refractory chronic GVHD without impairing disease control: A dual center retrospective analysis

Bone Marrow Transplantation volume 49, pages 1412–1418 (2014)Cite this article

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Abstract

Chronic GVHD (cGVHD) remains the most important cause of late non-relapse mortality post allogeneic hematopoietic SCT (HSCT). Although first-line treatment of cGVHD with steroids is well established, evidence for second-line treatment remains limited. Here, we report a dual center retrospective analysis of the off-label salvage treatment of steroid-refractory cGVHD with everolimus. Out of 80 patients with a median age of 50 (17–70) years, 14 (17%) suffered from mild, 39 (49%) from moderate and 27 (34%) from severe cGVHD. At the final analysis, median follow-up after introduction of everolimus was 724 (14–2205) days. Thirty-four patients (43%) required the addition of further immunosuppression during everolimus-based therapy. Global NIH Severity Score improved in 34 patients (43%), remained stable in 37 patients (46%) and worsened in 9 patients (11%). The total sum of Global NIH Severity Scores in all patients assessable was significantly reduced after treatment with everolimus (P<0.0001). Most frequent grade 3/4 toxicities included infections (n=30) and thrombocytopenia (n=15). There was a single case of relapse. Everolimus-based salvage treatment of refractory cGVHD results in significant improvement of the NIH Severity Score without impairing control of the malignant disease. Finally, these preliminary results demand further verification in prospective trials.

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Acknowledgements

We wish to thank our patients participating in this study. Parts of this work have been presented at the annual meeting of the American Society for Hematology (ASH) in Atlanta 2012.41 This work contains parts of the doctoral theses of JS and ML. We also thank Judy Peng, PhD, for critical reading of the manuscript.

Author contributions

SM and DW designed the study, provided patient care, analyzed data and wrote the paper; ML: collected and analyzed data, created figures and wrote the paper; JS: collected and analyzed data and contributed to the manuscript; DD and JA provided patient care and contributed to the manuscript; EH designed the study, provided patient care and contributed to the manuscript; MK, GUG and HE provided patient care and contributed to the manuscript.

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Author notes

  1. S Mielke and M Lutz: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine II, Allogeneic Stem Cell Transplantation Section, Würzburg University Medical Center, Würzburg, Germany

    S Mielke, M Lutz, M Kapp, H Einsele & G U Grigoleit

  2. Department of Internal Medicine III, Regensburg University Medical Center, Regensburg, Germany

    J Schmidhuber, D Ditz, J Ammer, E Holler & D Wolff

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  1. S Mielke
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Correspondence to S Mielke.

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Competing interests

SM received honoraria and travel grants from Novartis, Germany. DW and EH received research funding from Novartis, Germany. ML, JS, MK, DD, JA, HE and GUG declare no conflict of interest.

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Mielke, S., Lutz, M., Schmidhuber, J. et al. Salvage therapy with everolimus reduces the severity of treatment-refractory chronic GVHD without impairing disease control: A dual center retrospective analysis. Bone Marrow Transplant 49, 1412–1418 (2014). https://doi.org/10.1038/bmt.2014.170

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