A Phase I Study of the Safety and Feasibility of Bortezomib in Combination With G-CSF for Stem Cell Mobilization in Patients With Multiple Myeloma

Background: We previously reported that administration of bortezomib (BTZ) after 4 days of granulocyte colony-stimulating factor (G-CSF) significantly augments mobilization in mice. We hypothesized that administration of BTZ at peak G-CSF mobilization in patients with multiple myeloma (MM) would be safe, augment mobilization, and have an in vivo purging effect on circulating myeloma cells. Patients and Methods: This was a phase I study using 3 dose levels of BTZ. G-CSF was administered for 5 days. On the evening of the fourth day, a single dose of BTZ was administered. Peripheral blood was drawn 1 to 2 hours before and 15 to 18 hours after BTZ administration (before day 5 G-CSF administration) to analyze the mobilization effect of BTZ. Standard apheresis was then performed starting on day 5. After mobilization, patients underwent autologous stem cell transplantation (ASCT) per institutional guidelines. Results: Ten patients were enrolled. There were no dose-limiting toxicities. Median peripheral blood CD34⁺ cells at day 4 before BTZ administration was 16 per microliter and 15 hours later was 32 per microliter suggesting that administration of BTZ at peak G-CSF mobilization augments the mobilization effect of G-CSF. The effect of BTZ on circulating MM cells was unclear. All patients had successful engraftment after ASCT. Conclusion: Administration of 1 dose of BTZ at peak G-CSF mobilization was safe and well tolerated, enhanced stem cell mobilization, and did not affect graft viability. The mobilization effect of BTZ at peak G-CSF mobilization shown in this phase I study needs to be confirmed in a larger randomized trial.