Meloxicam with Filgrastim may Reduce Oxidative Stress in Hematopoietic Progenitor Cells during Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Multiple Myeloma.

Autologous stem cell transplantation (ASCT) is a potentially curative therapy but requires collection of sufficient blood stem cells (PBSC). Up to 40 % of patients with multiple myeloma (MM) fail to collect an optimum number of PBSC using filgrastim only and often require costly plerixafor rescue. The nonsteroidal anti-inflammatory drug meloxicam mobilizes PBSC in mice, nonhuman primates and normal volunteers, and has the potential to attenuate mobilization-induced oxidative stress on stem cells. In a single-center study, we evaluated whether a meloxicam regimen prior to filgrastim increases collection and/or homeostasis of CD34+ cells in MM patients undergoing ASCT. Mobilization was not significantly different with meloxicam in this study; a median of 2.4 × 106 CD34+ cells/kg were collected in the first apheresis and 9.2 × 106 CD34+ cells/kg were collected overall for patients mobilized with meloxicam-filgrastim, versus 4.1 × 106 in first apheresis and 7.2 × 106/kg overall for patients mobilized with filgrastim alone. CXCR4 expression was reduced on CD34+ cells and a higher CD4+/CD8+ T-cell ratio was observed after mobilization with meloxicam-filgrastim. All patients treated with meloxicam-filgrastim underwent ASCT, with neutrophil and platelet engraftment similar to filgrastim alone. RNA sequencing of purified CD34+ cells from 22 MM patients mobilized with meloxicam-filgrastim and 10 patients mobilized with filgrastim only identified > 4,800 differentially expressed genes (FDR < 0.05). Enrichment analysis indicated significant attenuation of oxidative phosphorylation and translational activity, possibly mediated by SIRT1, suggesting meloxicam may counteract oxidative stress during PBSC collection. Our results indicate that meloxicam was a safe, low-cost supplement to filgrastim mobilization, which appeared to mitigate HSPC oxidative stress, and may represent a simple means to lessen stem cell exhaustion and enhance graft quality.