Effect Of Bortezomib, Cyclophosphamide, And Filgrastim On Complete Remission Rates And Cd34+Stem Cell Collections In Multiple Myeloma (Mm)

8587 Background: Typical stem cell mobilization regimens in MM include G-CSF alone or with high-dose cyclophosphamide. Given the known in vitro/in vivo synergy between bortezomib (Velcade [Vel]) and alkylating agents, we investigated the potential for concurrent cytoreduction by adding Vel to the mobilization regimen. Methods: Primary objectives of this open-label study were to maximize response pre-transplant and the successful mobilization and harvest of stem cells (goal ≥10 × 106/kg in <7 leukaphereses). Eligible patients (pts) had symptomatic, Durie-Salmon stage II/III MM. All pts received six 21-day cycles of Vel/dexamethasone ± liposomal doxorubicin. Mobilization comprised Vel 1.3 mg/m2 on days 1, 4, 8, and 11, cyclophosphamide 3 g/m2 on day 8, and filgrastim (rhG-CSF) for 10 days from day 9. Time to post-transplant ANC (>1.5 × 109/L) and platelet (>20 × 109/L) recovery were recorded. Results: Of 24 pts accrued, 14 have been mobilized, and 10 have completed transplant. CD34+ yields greatly exceeded the study goal (table). Median CD34+ collection was 21.3 ×106/kg in a median of 1.5 collection days. Of the 23 evaluable pts 70% had ≥ PR, with 48% CR/nCR. Pts who had not achieved a complete response (CR) prior to mobilization continued to respond positively to treatment during mobilization, including one transition from near-CR to CR and one from stable disease to partial response. Expected grade 3/4 toxicities occurred; no pts discontinued mobilization. Post-transplant, median time to ANC recovery was 11 days and to platelet recovery was 18 days. Correlative studies of biomarkers for stem cell mobilization comparing Vel mobilized to non Vel mobilized stem cells (CD34, gene array analysis, CXCR2–4) will be presented. Conclusion: Vel, cyclophosphamide, and filgrastim is a novel, well tolerated, and effective regimen for stem cell mobilization in MM. It results in high stem cell yields in a short collection time and provides the potential for further cytoreduction. CD34+ stem cell collection and engraftment data by patient Patient Days to collection Days to meet study goal (10 x 106/kg) * CD34+ stem cells (x 106/kg) Days to ANC recovery Days to platelet recovery 1 18 1 21.2 14 20 2 17 1 47.4 11 13 3 19 1 22.0 13 22 4 18 1 17.9 10 15 5 19 3 40.6** 11 21 6 18 1 19.9 10 16 7 19 1 294.2*** 10 17 8 17 2 13.8 13 24 9 18 5 9.3 11 18 10 17 2 21.4 16 15 11 17 1 50.0 12 21 1 66.1 13 18 1 30.4 14 17 1 43.6 * Median time to meet study goal was 1 day; ** Note: 20.4 x 106 cells collected after 2 days; *** Note: 86.3 x 106 cells collected after 1 day Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Millennium Millennium