Burixafor, a CXCR4 inhibitor with a differentiated kinetics profile: results of a phase 2 study for rapid cell mobilization in multiple myeloma and lymphoma patients undergoing transplant

Inhibitors of C-X-C Chemokine Receptor type 4 (CXCR4) are standard of care for mobilization of hematopoietic stem and progenitor cells (HPC) in transplant eligible patients with hematological malignancies or undergoing HPC-based gene therapies. Burixafor hydrobromide is a potent and selective CXCR4 Antagonist that has demonstrated rapid mobilization of CD34+ HPC with a favorable safety and pharmacokinetic profile across a wide dose range in healthy subjects. Here, a 12-participant, multi-center, open label phase 2 study was conducted, wherein burixafor (3.14 mg/kg) was administered in combination with G-CSF in participants with multiple myeloma (MM), non-Hodgkin’s lymphoma (NHL) and Hodgkin Disease (HD). Eleven of 12 participants (92%) met the primary endpoint of collecting ≥ 5.0 × 10⁶ CD34+ cells/kg within two leukapheresis sessions, with six participants achieving this goal in 1 apheresis. Median time to neutrophil and platelet engraftment were 12 and 22 days, respectively. Seven of the 12 participants experienced 10 treatment emergent adverse events (TEAEs), only 2 of which were deemed related to the study drugs. These were Grade 2 bone pain in 1 participant following G-CSF alone, and Grade 1 diarrhea in another participant following intravenously administered burixafor preceded by G-CSF. Interestingly, peak mobilization of CD34+ cells occurred within one hour after burixafor administration, faster than currently approved CXCR4 inhibitors. This allows for same-day collection, potentially reducing healthcare burden. These results support continued development of burixafor for HPC mobilization in hematologic malignancies and gene therapy indications, particularly in the context of an evolving treatment landscape. This study was registered on ClinicalTrials.gov (TRN: NCT02104427) on April 1, 2014.

Supplementary Information: The online version contains supplementary material available at 10.1007/s00277-026-06858-9.

Autologous stem cell mobilization; Burixafor; CXCR4; Hematopoietic malignancies; Transplant.