On-Demand Plerixafor Added to High-Dose Cyclophosphamide and Pegylated Recombinant Human Granulocyte Colony-Stimulating Factorin the Mobilization of Patients with Multiple Myeloma: High Effectiveness and Affordable Cost

Abstract

Background Autologous stem cell transplantation(ASCT) still represents an integral part of treatment for patients with eligible newly diagnosed multiple myeloma. It is important to collect enough stem cells for two transplants in the first mobilization.The combination of high-dose cyclophosphamide(Cy) (3g/m 2) plus granulocyte colony-stimulating factor(G-CSF)and on-demand plerixafor has been considered the effective method as mobilization regimen, but G-CSF requires daily, multi-injection administration. Here, we performed a real-world analysis to evaluate the efficacy and cost of high-dose Cy combination pegylated recombinant human granulocyte colony-stimulating factor（PEG-rhG-CSF）and on-demand plerixafor for the first time, allowing for a single injection given the long half-life and slow elimination of PEG-rhG-CSF. Methods We retrospectively compared 343 patients whith MM mobilized between August 2008 and December 2022 using the following mobilization strategies: Cy+PEG-rhG-CSF+/-plerixafor(n=61), Cy+PEG-rhG-CSF(n=89),Cy+ G-CSF( n=169), G-CSF+plerixafor(n=24). Then the stem cell mobilization and collection results of the four groups were compared. Results Mobilization with Cy+PEG-rhG-CSF+/-plerixafor resulted in a significantly higher total CD34+ cells ( ×10 6/kg )collected( 8.81) compared to patients mobilized with other mobilization regimens：Cy+PEG-rhG-CSF(5.47；p＜0.001),Cy+ G-CSF(4.65; p＜0.001), G-CSF+plerixafor( 2.99; p＜0.001). Day1+Day 2 CD34+ cells ( ×10 6/kg ) collected were higher in Cy+PEG-rhG-CSF+/-plerixafor group too (Cy+PEG-rhG-CSF+/-plerixafor, 7.87 vs. Cy+PEG-rhG-CSF, 4.96 vs. Cy+ G-CSF,3.92 vs. G-CSF+plerixafor, 2.43) (p＜0.001).The percentage of patients who achieved＞6×10 6/kg CD34+ cells were significantly higher in Cy+PEG-rhG-CSF+/-plerixafor group group (77.0%) than other mobilization regimens：Cy+PEG-rhG-CSF (42.7% ；p＜0.001),Cy+ G-CSF( 37.3% ;p＜0.001）, G-CSF+plerixafor( 8 % ;p＜0.001). Apheresis sessions were fewer in Cy+PEG-rhG-CSF+/-plerixafor group ( Cy+PEG-rhG-CSF+/-plerixafor, 2 vs. Cy+PEG-rhG-CSF,3 vs. Cy+ G-CSF ,3 vs. G-CSF+plerixafor,4)(p＜0.001). Patients proceeded to ASCT with a mean of 2.94 CD34+cell (×10 6/kg ) infused for PEG-rhG-CSF+/-plerixafor , 2.94 infused for Cy+PEG-rhG-CSF, 2.61infused for G-CSF+plerixafor, 3.17 infused for Cy+ G-CSF (p=0.057) . The median time to neutrophil and platelet engraftment not different in the four groups. The total cost of mobilization and apheresis using Cy+PEG-rhG-CSF+/-plerixafor was significant lower ($5670.64) compared to G-CSF+plerixafor group($11098.61), and significant higher than Cy+PEG-rhG-CSF group ($3842.23)and Cy+ G-CSF group($3727.82)（p＜0.001）. Multivariate analysis showed that patients who received Cy+PEG-rhG-CSF +/-plerixafor treatment had significantly higher likelihoods of successfully achieving the optimal harvest (6×10 6/kg) in respect to Cy+PEG-rhG-CSF group mobilized without any plerixafor. The incremental cost-effectiveness ratio, for each 1% increase in probability of achieving a successful optimal harvest, was $62.57 per patient. The incidence of neutropenic fever not different in the Cy+PEG-rhG-CSF+/-plerixafor group(4%), Cy+PEG-rhG-CSF group (10%) and Cy+ G-CSF group(18%)(p=0.051). There was no patients suffered with neutropenic fever in G-CSF+plerixafor group. Conclusion Given higher rates of successful mobilization, affordable cost and toxicity, on-demand plerixafor added to high-dose Cy and PEG-rhG-CSF may be preferable in the mobilization of patients with multiple myeloma.