Effects of in vivo CXCR4 blockade and proteasome inhibition on bone marrow plasma cells in HLA-sensitized kidney transplant candidates

To date, plasma cell (PC)-targeted therapies have been limited by suboptimal PC depletion and antibody rebound. We hypothesized this is partly because of PC residence in protective bone marrow (BM) microenvironments. The purpose of this proof-of-concept study was to examine the effects of the CXCR4 antagonist, plerixafor, on PC BM residence; its safety profile (alone and in combination with a proteasome inhibitor, bortezomib); and the tran-scriptional effect on BMPCs in HLA-sensitized kidney transplant candidates. Participants were enrolled into 3 groups: group A (n = 4), plerixafor monotherapy; and groups B (n = 4) and C (n = 4), plerixafor and bortezomib combinations. CD34+ stem cell and PC levels increased in the blood after plerixafor treatment. PC recovery from BM aspirates varied

Automated summary

This study suggests that the limited effectiveness of plasma cell-targeted therapies may be due to the protective bone marrow microenvironments. The CXCR4 antagonist, plerixafor, has shown potential in altering plasma cell residence in the bone marrow, thereby enhancing treatment outcomes. The study also explores the transcriptional effects of plerixafor in combination with the proteasome inhibitor, bortezomib, in HLA-sensitized kidney transplant candidates.