Hematopoietic Stem Cell Mobilization for Allogeneic Stem Cell Transplantation by Motixafortide, a Novel CXCR4 Inhibitor.

Peripheral blood stem cells are the most common source of hematopoietic stem and progenitor cells (HSPCs) used for hematopoietic cell transplantation (HCT). HSPC mobilization with G-CSF +/- plerixafor results in suboptimal HSPC yields in up to 30% of patients, despite multiple injections and leukapheresis procedures (LP). We evaluated motixafortide (BL-8040), a high-affinity, long-acting CXCR4 inhibitor with rapid mobilizing kinetics, in a multi-center, open-label, single-arm, 2-part, Phase II study to mobilize HSPCs in allogeneic HCT donors (NCT02639559). The primary endpoint was the efficacy of 1 dose of motixafortide to mobilize greater than or equal to 2.0×10^6 CD34+ cells/kg within 2 LPs. Twenty-five donor-recipient pairs were enrolled. Motixafortide was well-tolerated with 22/24 (92%) evaluable donors meeting the primary endpoint, including 11/11 donors receiving motixafortide at 1.25mg/kg. Engraftment and GVHD rates were comparable to historical data. Motixafortide preferentially mobilized large numbers of multipotent HSPCs and a smaller proportion of CD34+ plasmacytoid dendritic cell precursors with high CD123 expression. Motixafortide induced pan-mobilization of all major myeloid and lymphoid subsets, with maximum relative changes in plasmacytoid/myeloid dendritic cells, B-cells, basophils, CD8 T-cells and classical monocytes. In conclusion, a single injection of motixafortide results in rapid and sustained mobilization of multipotent HSPCs for allogeneic HCT.