Moving Beyond G-CSF Mobilization-Learning From a 15-Year Experience of Different Stem Cell Mobilization Regimens in Multiple Myeloma.

Background: Stem-cell mobilization in multiple myeloma is usually done with G-CSF with or without Cyclophosphamide (Cy) based chemotherapy/Plerixafor. Pre-clinical data suggest the role of proteasome inhibitors in mobilization. We previously reported that Bortezomib (Bort) when added to a Cy-based regimen had a better stem-cell yield. Consequent to favorable results with Bort + Cy-G-CSF, we used Bortezomib with G-CSF too. Hence, four different mobilization regimens were used-Bort + G-CSF (Group-1); G-CSF + Plerixafor (Group-2); Bort - Cy-G-CSF (Group-3); Cy + G-CSF (Group-4). We report here our 15-year retrospective analysis of these 4 mobilization regimens.

Objectives: Primary objective was to determine proportion of patients with CD34 dose ≥ 5 × 10/kg in first apheresis in various groups. Secondary objectives were to determine median CD34 dose (×10/kg) in first apheresis, total median CD34 dose (×10/kg) of all harvests and frequency of mobilization failure. Mobilization failure was defined as total CD34 dose of < 2 × 10/kg or abandoned harvest attempt at physician's discretion after anticipating a poor collection.

Results: All consecutive patients with MM aged 18-65 years who underwent stem-cell mobilization from September 2007-December 2022 were included. In an intention-to-treat analysis, a total 200 patients with 205 mobilization attempts were analysed. The median age of the cohort was 48 years. The percentage of patients who collected ≥ 5 × 10 CD34 cells/kg in the first apheresis was 26%, 53%, 69%, and 63% in Groups 1-4, respectively (p = 0.0001). The median CD34 yield in the first harvest (×10/kg) was 3.62, 5.20, 6.04, and 6.05 in Groups 1-4, respectively (p = 0.00004). The median total stem-cell dose collected (×10/kg) was 5.73, 6.17, 9.14, and 8.23 in Groups 1-4, respectively (p < 0.00001). Mobilization failure rates were 7%, 3%, 0%, and 2%, respectively (p = NS).

Conclusion: Cyclophosphamide-based chemo-mobilization regimens with or without Bortezomib have the advantage of higher total stem-cell yield, while they are equivalent to G-CSF + Plerixafor for harvest in a single apheresis. The addition of Bortezomib to Cyclophosphamide may help to increase stem cell yield.