A Pilot, Exploratory, Randomized, Phase II Safety Study Evaluating Tumor Cell Mobilization and Apheresis Product Contamination in Patients Treated with Granulocyte Colony-Stimulating Factor Alone or Plus Plerixafor

Abstract

Because of the potential risk of tumor cell mobilization with granulocyte colony-stimulating factor (G-CSF), it is crucial to evaluate any potential effect of plerixafor treatment in the presence of G-CSF on multiple myeloma (MM) cell mobilization. This was an open-label, multicenter, randomized, exploratory, safety study (NCT01753453) that investigated the extent of MM cell mobilization after treatment with G-CSF + plerixafor in patients who were deemed poor mobilizers of hematopoietic stem cells. The primary efficacy outcome was the number of MM cells in peripheral blood and apheresis product after G-CSF + plerixafor treatment versus G-CSF alone. Key secondary efficacy outcomes included overall survival and disease status up to 2years after the first G-CSF dose. Twenty patients were randomized and received at least 1 dose of study treatment. There were no patients with MM cells in peripheral blood up to day 8 G-CSF administration in either treatment group. Up to day 8 no patient in the G-CSF + plerixafor arm and only 1 patient in the G-CSF arm mobilized at least 4.5 × 10 MM cells in the apheresis product. Nine of 10 patients from each treatment arm proceeded to transplantation. MM cells were detected in 5 patients from each treatment arm before and after transplantation. Adverse events observed in the G-CSF + plerixafor arm were consistent with the known safety profile of plerixafor. No MM cells were detected in peripheral blood of either treatment group up to day 8 of mobilization. Only 1 patient in the G-CSF alone group mobilized at least 4.5 × 10 MM tumor cells in apheresis product up to day 8. However, 50% of patients in both treatment arms had detectable amounts of MM cells in their peripheral blood pre- and post-transplantation. There were no new safety concerns with plerixafor.

Results from a multicenter, noninterventional registry study for multiple myeloma patients who received stem cell mobilization regimens with and without plerixafor

“…Furthermore, a major concern in the mobilization of stem cells for transplantation is the potential risk of tumor cell mobilization. In this respect, a recent study reported that MM tumor cells were not detected in the apheresis products of patients who received either G-CSF + P or those who received G-CSF alone [20]. Collectively, the findings from these two studies further support the safety of G-CSF + P for mobilizing CD34+ cells for transplantation in poor mobilizers.…”

Efficacy of hematopoietic stem cell mobilization regimens in patients with hematological malignancies: a systematic review and network meta-analysis of randomized controlled trials

“…2006 MM G-CSF SD; G-CSF SD + Plerixafor SD The Plerixafor group showed significantly higher rate of achieving optimal target ( P < 0.001)* and higher CD34 + cells collected Matsue et al [ 48 ] Phase 2 RCT, open-label, multicenter Nov. 2014–Mar. 2016 NHL G-CSF SD; G-CSF SD + Plerixafor SD The Plerixafor group showed higher rate of achieving optimal target Nahi et al [ 50 ] Phase 2 RCT, open-label, multicenter NA MM G-CSF SD; G-CSF SD + Plerixafor SD The Plerixafor group showed higher CD34 + cells yield Ri et al [ 55 ] Phase 2 RCT, open-label, multicenter Oct. 2014–Jul. 2015 MM G-CSF SD; G-CSF SD + Plerixafor SD The Plerixafor group showed higher rate of achieving optimal target Zhu et al [ 66 ] Phase 3 RCT, double-blind, multicenter Apr.…”

Tumor Dormancy: Biologic and Therapeutic Implications

“…For example, multiple myeloma patients were studied where HSCs were mobilized with granulocyte colony-stimulating factor (G-CSF) to increase the numbers of mobile monoclonal plasma cells [ 11 ]. However, adding CXC-chemokine receptor 4 (CXCR4) antagonist, which blocks binding of CXC-chemokine ligand 12 (CXCL12), to G-CSF did not change the rate of cancer cell immobilization in multiple myeloma patients [ 12 ]. CXCL12 has been suggested to regulate most aspects of HSC maintenance, proliferation, localization, and self-renewal, which exists in cells that make up the niche within which these dormant cells reside [ 13 ].…”

“…Vora [11] 1994 A pilot, exploratory, randomized, phase II safety study evaluating tumor cell mobilization and apheresis product contamination in patients treated with granulocyte colony-stimulating factor alone or plus plerixafor Nahi [12] 2019 CXCR4 is required for the quiescence of primitive hematopoietic cells.…”