Mobilization of Hematopoietic Progenitor Cells with Standard- or Reduced-Dose Filgrastim after Vinorelbine in Multiple Myeloma Patients: A Randomized Prospective Single-Center Phase II Study

Abstract

Vinorelbine combined with filgrastim at a dose of 10 µg/kg of body weight (BW) per day is a reliable and well-tolerated regimen for mobilization of hematopoietic progenitor cells (HPCs) in patients with multiple myeloma. This prospective, randomized, phase II study was initiated to assess the feasibility of a reduced filgrastim dosage. Vinorelbine was combined with either standard-dose filgrastim (10 µg/kg BW per day) or reduced-dose filgrastim (5 µg/kg BW per day). Leukapheresis sessions were planned to start at day 8 and were continued until the predefined target amount of 4 × 10 HPCs/kg BW was collected. The study demonstrated the feasibility of vinorelbine combined with reduced daily filgrastim with a mean of 1.29 leukapheresis sessions necessary per patient (95% confidence interval, .95 to 1.7). All patients could start leukapheresis as planned at day 8, and the collection success rate was 100% for the whole patient collective after a maximum of 2 leukapheresis sessions. No statistically significant differences with regard to the amount of HPCs collected between the 2 groups were observed (P = .99). Accordingly, no differences were seen with regard to length of hospitalization for autotransplant (P = .34) and duration of neutrophil (P = .93) and platelet engraftment (P = .42). Patients receiving reduced-dose filgrastim reported significantly lower peak pain values in a numeric analogue scale (P = .01), and the costs were significantly lower than in patients undergoing standard-dose chemomobilization (P = .001). Vinorelbine 35 mg/m plus filgrastim 5 µg/kg BW once per day until completion of HPC collection is feasible and appears to be advantageous with respect to the severity of pain intensity and treatment costs.

Efficacy of hematopoietic stem cell mobilization regimens in patients with hematological malignancies: a systematic review and network meta-analysis of randomized controlled trials

“…After excluded studies of cost-effectiveness analysis and post-hoc analysis, and studies that included other diseases, 44 trials were included for systematic review [ 24 – 67 ]. For further evaluation, different doses of G-CSF or Biosimilar G-CSF are classified into 2 groups as previously described: standard dose (SD, 10 μg/kg/day or 400 μg/m 2 /day), reduced dose (RD, 5–7.5 μg/kg/day or 250 μg/m 2 /day) [ 57 , 68 ]. Different doses of plerixafor are classified as SD (standard dose, 0.24 mg/kg/day) and FD (fixed dose, 20 mg/day).…”

“…2004 MM or NHL CY or ESHAP (± Rituximab) + G-CSF SD (single-dose versus split-dose) No significant differences in the number of CD34 + cells collected ( P = 0.47) and rate of reaching optimal target ( P = 0.24) Kuruvilla et al [ 43 ] Phase 4 RCT, open-label, multicenter Oct. 2010–Feb. 2013 NHL G-CSF SD + Plerixafor SD; G-CSF SD + Plerixafor FD No significant differences in the rate of achieving optimal target ( P = 0.395) Ozcelik et al [ 53 ] RCT, single center 2005–2008 NHL or MM CE + G-CSF SD (early versus late) No significant differences in the number of CD34 + cells collected ( P = 0.781) Samaras et al [ 57 ] Phase 2 RCT, single center 2011–2016 MM Vinorelbine + G-CSF SD; Vinorelbine + G-CSF RD No significant differences in the number of CD34 + cells collected ( P = 0.99) Others Copelan et al [ 29 ] RCT, single center May. 2000–Apr.…”

“…However, RCT that directly compare the mobilization efficacy of ID-AraC versus CY is unavailable. In addition, it is suggested that some countries commonly used another chemotherapeutic agent vinorelbine plus G-CSF as standard HSCs mobilizaion regimen for patients with MM [ 38 , 57 ]. Well-designed RCTs comparing these regimens will be helpful to establish our results and determine the optimal mobilization regimens for MM patients.…”

Stem Cell Mobilization with Ixazomib and G-CSF in Patients with Multiple Myeloma

“…As compared to cyclophosphamide, which has been classically used in several MM mobilization studies, vinorelbine is associated with lower rates of adverse events and infectious complications and can be easily administered in the outpatient setting. Moreover, stem cell mobilization with vinorelbine leads to a predictable CD34+ cell peak at day 8 [6,25,26]. Still, vinorelbine entails a relevant risk of neurotoxicity [27].…”

“…In Switzerland, the standard regimen for stem cell mobilization is a combination of vinorelbine and G-CSF. Some advantages of vinorelbine, as compared to cyclophosphamide, are the good predictability of the stem cell collection at day 8, the feasibility of outpatient management and a lower rate of infectious complications [6,25,26].…”