plerixafor

Agonists induced transient heteromerization coupled to receptor internalization, while antagonists, especially plerixafor together with maraviroc, stabilized persistent surface-associated complexes. Molecular dynamics simulations in asymmetric bilayers resembling MDA-MB-231 and MCF-10A membranes identified cholesterol-enriched receptor interfaces that prolong CXCR4-CCR5 dimer lifetimes in MDA-like membranes. These results show that GPCR heteromerization is not an intrinsic fixed property of receptor pairs, but an emergent behavior shaped by cell state, lipid environment, and ligand input.

Mobilizing peripheral blood stem cells in lymphoma patients with a single high-dose of etoposide combined with mecapegfilgrastim is effective, safe and cost-effective.

P2, N=74, Not yet recruiting, National Cancer Institute (NCI)

P1, N=12, Not yet recruiting, St. Jude Children's Research Hospital

P1, N=66, Active, not recruiting, Stanford University | Recruiting --> Active, not recruiting | Trial completion date: Nov 2027 --> May 2028 | Trial primary completion date: Nov 2027 --> May 2028

In our cohort, the incorporation of ASCT into multimodality therapy was feasible with resource-adapted strategies; however, this did not translate into a meaningful improvement in survival outcomes when compared with our historical non-transplant cohort.

Preclinical studies demonstrate that CXCR4 antagonists (e.g., plerixafor, LY2510924) suppress metastasis and, when combined with immune checkpoint inhibitors, can reverse the "cold" immune phenotype of microsatellite-stable CRC. We also discuss recent advances in the regulation of CXCL12/CXCR4 expression, the role of related receptors such as CXCR7, and emerging strategies targeting this axis for therapeutic intervention. Collectively, current evidence supports the CXCL12/CXCR4 axis as a promising biomarker and therapeutic target in metastatic CRC, and further elucidation of its regulatory network may facilitate the development of more effective precision treatment strategies.

P1/2, N=8, Active, not recruiting, City of Hope Medical Center | Trial completion date: Feb 2026 --> Feb 2027

P=N/A, N=10, Recruiting, Northwell Health | Initiation date: Oct 2025 --> Jun 2026

Treatment with AMD3100, a CXCR4 antagonist, partially restored vascular abnormalities caused by VHL deletion in ECs. Additionally, publicly available single-cell RNA-sequencing data from ECs of patients with VHL syndrome supports our findings, indicating that VHL mutations in ECs contribute to abnormal angiogenesis through ectopic activation of the HIF-CXCR4 signaling axis.

In our real-life study, we confirmed the strong negative impact of lenalidomide on PBSC collection by comparing lenalidomide-treated patients with a control cohort of thalidomide-treated subject, also showing a more frequent use of plerixafor to mitigate these effects, thereby reducing the reliance on cyclophosphamide, that was associated with lower risk of prolonged apheresis sessions. Indeed, we showed that lenalidomide use significantly impaired stem cell collection, with prolonged apheresis sessions and lower CD34+ cell collection on day 1, while post-transplant outcomes did not significantly differ between groups. Our real-life bi-center experience is of great interest in the era of daratumumab-based regimens as first-line therapy for autologous stem cell transplantation-eligible MM patients, because the concomitant use with lenalidomide might negatively affect PBSC mobilization, urging for more tailored PBSC collection strategies.

Although Dara-VTd induction is associated with impaired mobilization kinetics, successful steady-state mobilization remains feasible. On-demand plerixafor use overcomes mobilization deficits, supporting this approach in patients receiving CD38-based quadruplet induction therapy. Furthermore, follow-up analysis of stem cell graft utilization demonstrates a high proportion of collected but unused stem cell grafts in both cohorts.