Plerixafor: A chemokine receptor-4 antagonist for mobilization of hematopoietic stem cells for transplantation after high-dose chemotherapy for non-Hodgkin's lymphoma or multiple myeloma

Abstract

Background: Autologous hematopoietic stem cell (HSC) transplantation is used to facilitate hematopoietic recovery after administration of high-dose chemotherapy in patients with Hodgkin's disease, non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), leukemias, and some solid tumors. There are limitations to the existing methods of mobilizing CD34+ HSC with chemotherapy and/or granulocyte colony-stimulating factor (G-CSF). Plerixafor, a bicyclam molecule that acts as a pure antagonist of chemokine receptor-4, is approved by the US Food and Drug Administration for use in combination with G-CSF for mobilization of CD34+ HSC in patients with NHL or MM.

Objective: This review presents information on plerixafor, including its mechanism of action in mobilizing stem cells, pharmacokinetics, clinical efficacy, adverse effects, and pharmacoeconomic considerations.

Methods: MEDLINE, EMBASE (1996-June 2009), and International Pharmaceutical Abstracts (1970-June 2009) were searched on July 9, 2009, using the key words plerixafor and AMD3100 for reports relating to HSC mobilization. The search was updated on September 20, 2009, and again on January 30, 2010. The reference lists of identified articles were examined for additional abstracts and other sources of information. The journal Blood was searched online to identify abstracts presented at Annual Meetings of the American Society of Hematology.

Results: After administration of plerixafor, HSC migrate from the bone marrow into the peripheral blood, permitting collection by apheresis. Clinical trials in humans have found that the combination of G-CSF + plerixafor facilitates mobilization of HSC. In patients with MM without extensive previous treatment who were undergoing a first mobilization, the use of G-CSF + plerixafor was reported to double counts of circulating peripheral CD34+ HSC and thus double the number of CD34+ HSC collected in half as many apheresis procedures, although rates of engraftment, graft durability, transplantation, and survival outcomes were not significantly improved. In patients with Hodgkin's disease or NHL, in whom limited success in mobilization is expected, G-CSF + plerixafor also facilitated or improved mobilization with improved apheresis yields, again without significant improvement in outcomes. Common (> or = 20%) adverse events of plerixafor used in combination with G-CSF include diarrhea (37%), nausea (34%), injection-site reactions (34%), fatigue (27%), and headache (22%). Plerixafor 0.24 mg/kg SC is administered on the evening of the fourth day of G-CSF dosing, approximately 11 hours before the first apheresis session. Daily doses of plerixafor can be repeated up to 3 times on consecutive days to achieve adequate HSC collection. The average wholesale price of a 24-mg vial of plerixafor is $7500.

Conclusions: Plerixafor is an effective agent for mobilizing CD34+ HSC. Long-term treatment outcomes are being studied in patients undergoing autologous transplantation of HSC mobilized with G-CSF + plerixafor.