Plerixafor and granulocyte colony-stimulating factor for first-line steady-state autologous peripheral blood stem cell mobilization in lymphoma and multiple myeloma: results of the prospective PREDICT trial

Abstract

© F e r r a t a S t o r t i F o u n d a t i o nalone or with chemotherapy, and the potential for toxicities and infection with chemotherapy-based mobilization highlighted the need to develop novel mobilization agents. 6,10 Plerixafor is a novel bicyclam small-molecule that reversibly binds to chemokine receptor CXCR4 and antagonizes the chemokine stromal cell-derived factor-1α (SDF-1α) interaction. 173 Plerixafor is approved by the Food and Drug Administration in combination with G-CSF to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with NHL and MM. 12,13 Comparatively, the approved indication for plerixafor in Europe is in combination with G-CSF for mobilization of hematopoietic stem cells for autologous transplantation in patients with lymphoma and MM whose cells mobilize poorly.14 Two phase III, multicenter, double blind, placebo-controlled, randomized clinical studies were conducted in the USA to evaluate the safety and efficacy of plerixafor 0.24 mg/kg plus G-CSF versus placebo plus G-CSF when used to mobilize CD34 + stem cells. The two studies enrolled patients with NHL and MM who had not previously had unsuccessful stem cell collections nor received prior stem cell transplants. In both studies, the combination of plerixafor plus G-CSF was safe and well tolerated and the efficacy results demonstrated that plerixafor plus G-CSF mobilized significantly higher numbers of hematopoietic stem cells and allowed collection of higher numbers of stem cells in fewer days of apheresis compared to G-CSF alone. 12,13 The vast majority of sites for both studies were located in the USA, with the exception of one center in Germany which enrolled ten patients with MM. Prior to carrying out this study, there was a paucity of data about the use of plerixafor as a first-line mobilization agent in the European Union, where clinical practices and patients' characteristics are different from those in the USA. The purpose of this multicenter, open label, single-arm study was to further investigate the safety and efficacy of plerixafor plus G-CSF for first-line mobilization in European patients with lymphoma or multiple myeloma. Design and Methods Study design and patientsThis was a multicenter, open label, single-arm study that evaluated the safety and efficacy of plerixafor in patients with NHL, HD, or MM. The study was divided into three time periods: period 1 (mobilization and apheresis): from the first G-CSF dose up to 30 days after the last plerixafor dose or until the first dose of chemotherapy (whichever was earlier); period 2 (high-dose ablative chemotherapy and transplantation): first day of high-dose chemotherapy to first day of engraftment; and period 3 (posttransplantation): engraftment to the 12-month follow-up.This study was conducted in accordance with the International Conference on Harmonization, Good Clinical Practice guidelines, the European Union Clinical Trial Directive, and the principles defined in the Declaration of...

Plerixafor plus pegfilgrastim is a safe, effective mobilization regimen for poor or adequate mobilizers of hematopoietic stem and progenitor cells: a phase I clinical trial

“…Adverse events were mild and acceptable, and comparable with published data on the more commonly used plerixafor/filgrastim combination, 22 and all patients self-injected at Table 3. CD34+ yields and kinetics-study group vs historical controls Plerixafor plus pegfilgrastim patients Pegfilgrastim-alone historical controls…”

Plerixafor prescription modalities in autologous haematopoietic stem cell mobilization in Belgium

“…For the Belgian patients included in this European Compassionate Use Program, a success rate of 64% in a mean of two apheresis sessions has been reported, 20 which is in line with the observation in this registry in the group of patients with known mobilization failure (63%). Plerixafor use in a first mobilization attempt has been described by Russell et al 21 who has reported results of the European multicentre PREDICT trial in which plerixafor was used in first line in all mobilization attempts. Success rate was 96% in a median of 1 day of apheresis (range 1-3).…”

Clinical Updates in Blood and Marrow Transplantation in Multiple Myeloma

“…Engraftment is established when the absolute neutrophil count is greater than 500 cells/ dl for three consecutive days or greater than 1,000 cells/dl for one day, and platelets remain greater than 20,000 cells/ dl, independent of platelet transfusions for at least seven days (DiPersio, Stadtmauer, et al, 2009). About three weeks (days +17 to +25) following infusion of HSCs, most acute toxicities, including myelosuppression related to the HDC, have resolved (Russell et al, 2013). Once the patient has no evidence of infection, has demonstrated engraftment, and establishes the ability to maintain oral hydration and nutrition, arrangements can be made for discharge (Pallera & Schwartzberg, 2004).…”