FDA review summary: Mozobil in combination with granulocyte colony-stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation

Oncology. 2010;78(3-4):282-8. doi: 10.1159/000315736. Epub 2010 Jun 8.

Abstract

Purpose: On December 15, 2008, the US Food and Drug Administration approved plerixafor (Mozobil; Genzyme Corp.), a new small-molecule inhibitor of the CXCR4 chemokine receptor, for use in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). This summary reviews the database supporting this approval.

Experimental design: The safety and efficacy of plerixafor were demonstrated by 2 multicenter, randomized, placebo-controlled studies in patients with NHL and MM who were eligible for autologous HSC transplantation. The primary efficacy end points were the collection of > or = 5 x 10(6) CD34+ cells/kg from the peripheral blood in 4 or fewer apheresis sessions in patients with NHL or > or = 6 x 10(6) CD34+ cells/kg from the peripheral blood in 2 or fewer apheresis sessions in patients with MM.

Results: The 2 randomized studies combined enrolled 600 patients (298 with NHL and 302 with MM). Fifty-nine percent of patients with NHL who were mobilized with G-CSF and plerixafor had peripheral blood HSC collections of > or = 5 x 10(6) CD34+ cells/kg in 4 or fewer apheresis sessions, compared with 20% of patients with NHL who were mobilized with G-CSF and placebo (p < 0.001). Seventy-two percent of patients with MM who were mobilized with Mozobil and G-CSF had peripheral blood HSC collections of > or = 6 x 10(6) CD34+ cells/kg in 2 or fewer apheresis sessions, compared with 34% of patients with MM who were mobilized with placebo and G-CSF (p < 0.001). Common adverse reactions included diarrhea, nausea, vomiting, flatulence, injection site reactions, fatigue, arthralgia, headache, dizziness, and insomnia.

Conclusions: This report describes the Food and Drug Administration review supporting the approval of plerixafor.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD34 / biosynthesis
  • Clinical Trials as Topic
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Hematopoietic Stem Cell Mobilization / methods*
  • Heterocyclic Compounds / administration & dosage*
  • Humans
  • Lymphoma, Non-Hodgkin / therapy
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / therapy
  • Placebos
  • Product Surveillance, Postmarketing
  • Randomized Controlled Trials as Topic
  • Receptors, CXCR4 / metabolism
  • United States
  • United States Food and Drug Administration

Substances

  • Antigens, CD34
  • CXCR4 protein, human
  • Heterocyclic Compounds
  • Placebos
  • Receptors, CXCR4
  • Granulocyte Colony-Stimulating Factor
  • plerixafor