Plerixafor (DB06809): A Comprehensive Monograph on a Pivotal Hematopoietic Stem Cell Mobilizer

Executive Summary

Plerixafor is a first-in-class, small-molecule, selective antagonist of the C-X-C chemokine receptor type 4 (CXCR4), which has fundamentally altered the clinical practice of hematopoietic stem cell (HSC) mobilization.[1] Marketed under the brand name Mozobil, and now available in generic formulations, it is indicated for use in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize HSCs into the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM).[1]

The development of plerixafor is a notable example of serendipity in drug discovery. Originally synthesized and investigated as an anti-HIV agent designed to block the CXCR4 co-receptor used by T-tropic viral strains, its clinical development for this indication was halted.[4] However, astute observation during early-phase trials revealed a consistent and marked elevation in circulating white blood cells, a phenomenon correctly identified as active HSC mobilization from the bone marrow.[4] This led to a strategic pivot, repositioning plerixafor as a hematologic agent.

Its primary clinical value lies in its ability to overcome the limitations of G-CSF alone, which fails to produce adequate stem cell yields in a significant percentage of patients, often termed "poor mobilizers".[2] By disrupting the CXCR4/SDF-1α axis that anchors HSCs in the marrow, plerixafor induces a rapid and predictable release of CD34+ cells into the periphery.[4] Pivotal clinical trials have demonstrated that the addition of plerixafor to a G-CSF regimen significantly increases the proportion of patients who achieve their target cell collection goals, often in fewer apheresis sessions, thereby reducing patient burden and healthcare resource utilization.[7]