Collecting healthy stem cells from patients with multiple myeloma, storing them, and re inputting them after high-dose chemotherapy can improve overall survival compared to traditional chemotherapy alone. This method is called autologous stem cell transplantation (ASCT), and its effectiveness depends on the ability to collect sufficient hematopoietic stem/progenitor cells (HSPCs), which typically come from the blood.
G-CSF (a protein that assists in the production of white blood cells and stem cells in the bone marrow) is a standard drug for mobilizing hematopoietic stem/progenitor cells (HSPCs) into the bloodstream for collection and storage. However, despite multiple days of treatment, 40-50% of patients with multiple myeloma are still unable to produce the optimal number of stem cells for autologous transplantation.
Motixafortide is a selective inhibitor of chemokine receptor CXCR4, which has been shown in phase 1 clinical trials to increase the abundance of HSPC in the circulating blood of healthy individuals.
On April 17, 2023, researchers from the University of Washington School of Medicine in St. Louis published a research paper in Nature Medicine titled "Motivation and G-CSF to mobile hematological stem cells for autologous transmission in multiple myeloma: a randomized phase 3 trial.
This phase 3 clinical trial reported that among 90% of 80 patients with multiple myeloma, injecting one dose of Motixafortide can safely mobilize the optimal number of stem cells for collection and transplantation. This method may improve the treatment outcomes of patients with multiple myeloma.
As part of a multicenter phase 3 study, the research team compared the safety and efficacy of mobilizing hematopoietic stem/progenitor cells (HSPCs) in 122 patients with multiple myeloma who were undergoing autologous stem cell transplantation, by combining Motixafortide with G-CSF and placebo with G-CSF.
The results indicate that Motixafortide+G-CSF is safe and well tolerated, with most adverse events occurring during treatment lasting only for a short period of time. In a single treatment of Motixafortide+G-CSF, 93% of patients with multiple myeloma (a total of 80 people) mobilized the optimal number of HSPCs for autologous stem cell transplantation, compared to 26% of patients (a total of 42 people) who achieved this effect in placebo+G-CSF. In addition, the author of the paper believes that Motixafortide+G-CSF has effectively mobilized more primary HSPCs, which are related to self-renewal and regenerative enhancement.
The authors of the paper conclude that these findings propose a new HSPC mobilization strategy that is fast, safe, and well tolerated, with the potential to greatly improve the ability to collect HSPCs for stem cell transplantation, as well as other HSPC based gene therapies.
