Background: In myeloma patients, a non-myelosuppressive regimen combining a single dose of vinorelbine chemotherapy together with G-CSF is safe and effective to harvest peripheral blood progenitor and stem cells (PBSC) before autologous stem cell transplantation (ASCT). Considering its neurotoxic potential, vinorelbine may aggravate pre-existing bortezomib-induced polyneuropathy, and gemcitabine represents an alternative mobilization regimen. We have reported that monotherapy with gemcitabine together with G-CSF can be used as a promising alternative mobilization chemotherapy to vinorelbine, even more so as gemcitabine avoids neurotoxicity associated with vinorelbine
Methods: In this prospective phase-II study (ViGeM Trial; NCT# 02791373), we compared in a 1:1 randomization the efficacy and toxicity of vinorelbine or gemcitabine with G-CSF (and, if needed, plerixafor) in 130 evaluable myeloma patients in first remission. The objective of the study is to demonstrate the non-inferiority of gemcitabine versus vinorelbine. The primary endpoint is mobilization success, which is defined as a collected apheresis product comprising at least 6.0×106 CD34+ cells/kg b.w. at day 8 after chemotherapy (vinorelbine or gemcitabine) together with G-CSF in the absence of plerixafor.
Results: We observed successful CD34+ mobilization in 75% [95% confidence interval (CI): 63%-85%] of patients in the vinorelbine group versus 49% [95% CI: 36%-62%] with gemcitabine; the pre-specified non-inferiority margin -15% was not reached. More vinorelbine recipients achieved the collection goal in a single-day procedure (78% vs 60%). The median CD34+ yield was 11.4×106/kg b.w. in vinorelbine versus 8.7×106/kg in gemcitabine (P=0.001). At apheresis as well as day +100 following ASCT, polyneuropathy occurred more frequent in vinorelbine recipients. Special attention should be given to the fact that no patients with gemcitabine was observed with grade ≥ 3 polyneuropathy (Table 1). Finally, less patients in the vinorelbine group (1%) needed two apheresis days as compared to 14% in the gemcitabine group, respectively (P=0.007), whereas the use of rescue plerixafor was similar (11% versus 10%).
Conclusion: This prospective comparison indicated that non-inferiority of gemcitabine as compared to vinorelbine chemotherapy together with G-CSF stimulation regarding CD34+ mobilization was not reached. Polyneuropathy was aggravated in the vinorelbine cohort, but not in gemcitabine recipients. Our study allows individualization of CD34+ mobilization regimens in myeloma patients.
No relevant conflicts of interest to declare.
Vinorelbine and gemcitabine are used for stem cell mobilization in this study and, thus, off-label.
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal