Co-Administration of Mgta-145 and Plerixafor Rapidly Mobilizes High Numbers of Hematopoietic Stem Cells and Graft-Versus-Host Disease Inhibiting Monocytic Cells in Non-Human Primates

Abstract

The majority of bone marrow transplants (BMTs) utilize granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood (mPB) as the source of hematopoietic stem cells (HSCs). Mobilization with G-CSF requires a multi-day dosing regimen and fails to mobilize a large proportion of CD34+CD90+CD45RA- HSCs, the cell type responsible for hematopoietic engraftment. Moreover, up to 80% of allogenic recipients will experience significant side effects such as acute graft-versus-host disease (GvHD), even though G-CSF mPB contains a small and variable number of immunosuppressive monocytes (Vendramin et al., BBMT 2014). Identification of a mobilizing regimen that consistently and rapidly produces high numbers of HSCs and immunosuppressive monocytes without the need for G-CSF would be ideal. We previously reported that MGTA-145, a CXCR2 agonist, rapidly mobilizes HSCs when combined with the CXCR4 inhibitor, plerixafor (Blood 2017 130:1920). In the present study, detailed profiling was performed at 0 through 24 hours after mobilization of non-human primates (NHPs) with a single dose of MGTA-145, plerixafor, or MGTA-145 plus plerixafor versus a multi-dose, five-day regimen of G-CSF. MGTA-145 plus plerixafor led to a 19-fold increase in number of CD34+CD90+CD45RA- HSCs within four hours of dosing (p As the risk of GvHD remains a significant clinical problem in the allogenic setting, MGTA-145 plus plerixafor may rapidly mobilize an advantageous graft relative to the standard of care, G-CSF, since MGTA-145 plus plerixafor results in significantly higher numbers of both engraftable HSCs and highly immunosuppressive monocytes.