Media release

From: Springer Nature

Cancer: Enhancing stem-cell mobilization for transplantation in multiple myeloma

A new compound, motixafortide, can safely mobilize an optimal number of stem cells for collection and transplantation in over 90% of 80 patients with multiple myeloma (a cancer of the bone marrow) with 1 injection, reports a phase 3 clinical trial published in Nature Medicine. This approach could improve treatment outcomes in patients with multiple myeloma.

Collection of a patient with multiple myeloma’s own healthy stem cells, to store and re-infuse after high dose chemotherapy, improves overall survival relative to conventional chemotherapy alone. The effectiveness of this approach, called autologous stem cell transplantation (ASCT), relies on the ability to collect sufficient hematopoietic stem and progenitor cells (HSPCs), typically from blood. G-CSF (a protein that aids the production of white blood cells and stem cells in the bone marrow) is the standard agent for mobilizing HSPCs to blood for collection and storage, but despite multiple days of treatment, 40–50% of patients with multiple myeloma remain unable to produce an optimal number of stem cells for ASCT. Motixafortide, a selective inhibitor of the chemokine receptor CXCR4, has been shown to increase the abundance of HSPCs in the circulating blood of healthy people in phase 1 clinical trials.

As part of a multi-center phase 3 study, Zachary Crees and colleagues compared the safety and efficacy of a combination of motixafortide and G-CSF versus placebo and G-CSF in 122 patients with multiple myeloma undergoing HSPC mobilization before ASCT. The results indicate that motixafortide plus G-CSF was safe and well tolerated, with most treatment-emergent adverse events lasting for a short time only. A single treatment with motixafortide added to G-CSF mobilized an optimal number of HSPCs for ASCT in 93% of patients with multiple myeloma (80 patients), compared with 26% in those treated with placebo and G-CSF (42 patients). Furthermore, the authors suggest that motixafortide and G-CSF preferentially mobilized larger numbers of primitive HSPCs, which are associated with enhanced self-renewal and regeneration.

These findings present a new HSPC-mobilization regime that is rapid, safe and well tolerated and has the potential to substantially improve the ability to collect HSPCs for stem cell transplantation, and other HSPC-based gene therapies, the authors conclude.