Hematopoietic Progenitor Cell (HPC) Mobilization after Initial Therapy of Multiple Myeloma Including Velcade: Ability to Collect HPC as a Function of Velcade Dosing

Bortezomib (Velcade) was recently approved by the US FDA for use as salvage therapy for patients with relapsed multiple myeloma (MM). We are conducting a clinical trial (Total Therapy 3) using VDT-PACE (velcade 1.0 mg/m2, dexamethasone 40 mg po QD day4–7, thalidomide 200 mg po QHS day 4–7, and continuous infusion of cisplatin 10 mg/m2, doxorubicin 10 mg/m2, and etoposide 40 mg/m2 day 4–7) and G-CSF at 5-8 mcg/Kg sc BID for initial therapy of MM as well as for mobilization of HPC for collection and use in autologous stem cell transplant. Initially, 20 patients (pts) were enrolled in 6 cohorts involving an escalating number of bortezomib doses: cohort 1 (5 pts) had 2 doses with cycle 1 and then underwent HPC collection; cohort 2 (3pts) had 3 doses with cycle 1 and then collection; cohort 3 (3 pts) had 4 doses with cycle 1 and then collection; cohort 4 (3 pts) had 4 doses with cycle 1, 2 doses with cycle 2 and then underwent HPC collection; cohort 5 (3 pts) had 4 doses with cycle 1 and 3 doses with cycle 2 and then collection; cohort 6 (3pts) had 4 doses with cycle 1 and 4 doses with cycle 2 and then collection. Further pts (cohort 7) were then treated and underwent HPC collection as for cohort 6. The protocol required a minimum of 2 HPC collections, and all patients underwent large volume leukapheresis using a Cobe Spectra when the peripheral blood CD34 measured by ProCount™ predicted a collection of ≥ 1 x 106/kg (Hematology (ASH Educat Progr) 2003; 419–37). HPC product contamination with malignant plasma cells was done using flow cytometry for cytoplasmic immunoglobulins (cIg). Patients who failed to mobilize adequately to support a tandem transplant were enrolled on a study utilizing G-CSF+AMD3100 for mobilization. HPC Collections by Cohort # Pts median # Collections (range) mean CD34x106/Kg (range) *1pt died before collection #1 pt switched to AMD3100 +6 pts switched to AMD3100 Cohort 1 5 2 31.2 (19.8–47.8) Cohort 2 3* 2 52.4 (45.1–59.6) Cohort 3 3 2 45.3 (31.9–80.5) Cohort 4 3 2 (2–3)# 22.9 (5.9–40.9) Cohort 5 3 2 (2–4) 44.8 (18.2–85.5) Cohort 6 3 2 (2–3) 36.1 (22.6–47.1) Cohort 7 24 3 (0–9)+ 17.5 (0–30.8) The median number of HPC collections for the first 6 cohorts overall was 2, and contamination as judged by cIg was very rare (2 of 19 who underwent collection). However, while 1 pt in cohort 4 failed to mobilize adequately with the planned regimen and required transfer to the secondary mobilization study, 6 of the first 24 pts in cohort 7 failed to mobilize and also required transfer to the secondary mobilization study. Of the first 27 patients evaluable after first transplant, both granulocyte and platelet recovery proceeded promptly. Because of the apparent dampening of cycle 2 PBSC mobilization, future patients are mobilized during cycle 1. Incorporation of Velcade into PBSC mobilization regimens should therefore proceed with caution.