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MEDTECH This article reviews the novel CXCR4 inhibitor motixafortide and its use in hematopoietic stem-cell mobilization. We present a history of stem-cell mobilization and update of recent innovations in novel mobilization strategies.
Hematopoietic stem-cell mobilization is a crucial step in autologous stem-cell transplantation. Motixafortide is a novel CXCR4 inhibitor that has been shown in preclinical and clinical trials to mobilize hematopoietic stem cells (HSCs) for transplantation. The drug has extended in vivo activity (>48 h) and high affinity (Ki, 0.32 nM).
In a phase 1, two-part study, motixafortide administered to healthy subjects was safe, well tolerated, and led to a rapid and robust increase in the number of circulating HSCs.
Motixafortide has been evaluated in a randomized phase 3 trial for autologous transplantation in multiple myeloma. The study showed that the combination of motixafortide and granulocyte colony-stimulating factor (G-CSF) was superior to G-CSF alone in terms of the number of CD34+ cells collected and the time to engraftment. The drug has also been evaluated in combination with plerixafor, another CXCR4 inhibitor, in a phase 1/2 study for autologous transplantation in multiple myeloma. The study showed that the combination of motixafortide and plerixafor was safe and effective in mobilizing HSCs.
Motixafortide has several advantages over other CXCR4 inhibitors. It has extended in vivo activity, which allows for a longer window of opportunity to collect HSCs. It also has a high affinity for CXCR4, which results in a more rapid and robust mobilization of HSCs. In addition, motixafortide has been shown to mobilize differential HSC subsets, which may have implications for transplantation outcomes.
In conclusion, motixafortide is a promising new CXCR4 inhibitor for hematopoietic stem-cell mobilization. It has been shown to be safe and effective in clinical trials and has several advantages over other CXCR4 inhibitors. Physicians should consider using motixafortide in combination with G-CSF or plerixafor for autologous transplantation in multiple myeloma.
