TY - JOUR
T1 - Bortezomib is safe in and stabilizes pulmonary function in patients with allo-HSCT-associated pulmonary CGVHD
AU - Jain, Manu
AU - Budinger, GRS
AU - Jovanovic, Borko
AU - Dematte, Jane
AU - Duffey, Sara
AU - Mehta, Jayesh
N1 - Funding Information:
The study was funded through an unrestricted research grant from Millennium Pharmaceuticals. The sponsors reviewed the manuscript prior to submission but did not contribute to study design, data analysis, interpretation, or writing of the manuscript.
Publisher Copyright:
© 2018, Macmillan Publishers Limited, part of Springer Nature.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - 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.
AB - 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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U2 - 10.1038/s41409-018-0134-4
DO - 10.1038/s41409-018-0134-4
M3 - Article
C2 - 29523886
AN - SCOPUS:85043307817
SN - 0268-3369
VL - 53
SP - 1124
EP - 1130
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 9
ER -