Phase III Prospective Randomized Double-Blind Placebo-Controlled Trial of Plerixafor Plus Granulocyte Colony-Stimulating Factor Compared With Placebo Plus Granulocyte Colony-Stimulating Factor for Autologous Stem-Cell Mobilization and Transplantation for Patients With Non-Hodgkin's Lymphoma

Abstract

Plerixafor and G-CSF were well tolerated and resulted in a significantly higher proportion of patients with non-Hodgkin's lymphoma achieving the optimal CD34+ cell target for transplantation in fewer apheresis days, compared with G-CSF alone.

Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data

“…Previous plerixafor trials have shown the drug to be generally safe and well tolerated in healthy volunteers, 29 HIV-positive individuals, 30 as well as in patients with MM and lymphoma. 17,18 The most common adverse events related to plerixafor in these studies were diarrhea, nausea/vomiting and injection site reactions. In our series, there were no cases of severe adverse events, and the safety profile of plerixafor was very similar to that previously reported in the registration trials, despite the potentially more severe background conditions of a CUP population with mobilization failures.…”

“…Graft durability rates were comparable in the plerixafor plus G-CSF and placebo plus G-CSF trial arms. 17,18 These outstanding results led to the approval of plerixafor to enhance PBSC mobilization in patients with lymphoma and MM (FDA), in particular for those who mobilize poorly (EMEA). Among all patients at risk to mobilize poorly, the subgroup most difficult to treat includes those patients who have already failed mobilization attempts.…”

“…16 The efficacy of plerixafor has been demonstrated in two blinded randomized phase III placebo-controlled studies in patients with MM and non-Hodgkin's lymphoma (NHL). 17,18 In both studies, the percentage of patients who reached the primary end point of X5 Â 10 6 CD34 þ cells per kg in NHL and X6 Â 10 6 CD34 þ cells per kg in MM, and who successfully engrafted, was significantly higher in the plerixafor group than in the placebo group: (1) 57 vs 19% of patients with NHL and (2) 70 vs 34% of patients with MM. Plerixafor registration trials excluded patients who had failed conventional mobilization attempts before consideration for trial entry.…”

Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation

“…The combination of G-CSF with AMD3100 enables a much larger proportion of non-Hodgkin's lymphoma and multiple myeloma patients who previously failed to mobilize sufficiently with G-CSF alone, to successfully mobilize and proceed with an autologous transplantation. 4,5 Ten years ago, the first studies revealing the mechanisms of HSC mobilization in response to G-CSF and cytotoxic drugs such as CYP were conducted in humans, primates and mice. 6 --9 These studies showed release of active proteases in the bone marrow (BM) in response to G-CSF or CYP.…”

Clinical experience with a simple algorithm for plerixafor utilization in autologous stem cell mobilization

“…1 Poor mobilization has been associated with disease status, extent of prior therapy, radiation, older age and myelotoxic agents, such as melphalan, fludarabine and lenalidomide [3][4][5][6] Plerixafor, a reversible CXCR4 antagonist, significantly increases the yield of CD34 þ peripheral blood cells in randomized studies, thereby enabling more patients to proceed to autologous transplant. 7,8 In lymphoma, 59% of patients in the plerixafor þ G-CSF arm collected X5 Â 10 6 CD34 þ progenitors/kg compared with 20% in the placebo þ G-CSF arm (Po0.001). 8 Similarly in multiple myeloma, significant increases in the number of patients achieving minimal and optimal stem cell target collections were demonstrated.…”