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Bortezomib is safe in and stabilizes pulmonary function in patients with allo-HSCT-associated pulmonary CGVHD

Bone Marrow Transplantation volume 53, pages 1124–1130 (2018)Cite this article

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Abstract

Pulmonary chronic graft-versus-host disease (p-CGVHD) following allogeneic HSCT is devastating with limited proven treatments. Although sporadically associated with pulmonary toxicity, the proteasome inhibitor bortezomib may be efficacious in p-CGVHD. We sought to establish safety and tolerability of bortezomib in pilot, open-label trial of patients with p-CGVHD. The primary endpoint was adverse events. Efficacy was assessed by comparing FEV1 decline prior to p-CGVHD diagnosis to during the bortezomib treatment period. The impact on pulmonary function testing of prior long-term bortezomib treatment in multiple myeloma (MM) patients was also assessed as a safety analysis. Seventeen patients enrolled in the pilot study with a mean time to p-CGVHD diagnosis of 3.36 years (±1.88 years). Bortezomib was well tolerated without early dropouts. The median FEV1 decline prior to the diagnosis of p-CGVHD was −1.06%/month (−5.36, −0.33) and during treatment was −0.25%/month (−9.42, 3.52). In the safety study, there was no significant difference in any PFT parameter between 73 patients who received bortezomib and 68 patients who did not for MM. Thus, we conclude that bortezomib has acceptable safety and tolerability in patients with compromised pulmonary function. The efficacy of proteosomal inhibition should be assessed in a large trial of chronic p-CGVHD patients.

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Acknowledgements

Manu Jain takes responsibility for the content of the manuscript including the data analysis.

Author contributions

MJ and JM had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. BJ provided the data analysis for the study and contributed to the writing of the manuscript. JD and SD contributed substantially to the interpretation and the writing of the manuscript.

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

    Manu Jain, GRS Budinger & Jane Dematte

  2. Division of Preventative Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

    Borko Jovanovic

  3. Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

    Sara Duffey & Jayesh Mehta

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  1. Manu Jain
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Correspondence to Manu Jain.

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Conflict of interest

JM reports having received honoraria from Millennium Pharmaceuticals, the manufacturer of bortezomib, for speaking on the use of bortezomib in myeloma. The remaining authors declare that they have no conflict of interest.

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Jain, M., Budinger, G., Jovanovic, B. et al. Bortezomib is safe in and stabilizes pulmonary function in patients with allo-HSCT-associated pulmonary CGVHD. Bone Marrow Transplant 53, 1124–1130 (2018). https://doi.org/10.1038/s41409-018-0134-4

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