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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 6 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 2 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., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Biosimilars are increasingly being licensed as equipotent drugs, although efficacy and safety data are not available for all clinical indications. Accordingly, the efficacy of the biosimilar filgrastim Zarzio® combined with vinorelbine for chemo-mobilization of CD34+ hematopoietic progenitor cells (HPC) in patients with multiple myeloma has not been evaluated yet. We compared the efficacy of vinorelbine combined with this biosimilar filgrastim for HPC mobilization to vinorelbine plus original filgrastim (Neupogen®). Overall, 105 multiple myeloma patients received vinorelbine 35 mg/m 2 intravenously on day 1 and either original filgrastim (n = 61;58%) or biosimilar filgrastim (n = 44;42%) at a dose of 5 µg per kg body weight (BW) twice daily subcutaneously starting day 4 until the end of the collection procedure. Leukapheresis was scheduled to start on day 8 and performed for a maximum of three consecutive days until at least 4 × 10 6 HPC/kg BW were collected. All patients proceeded to leukapheresis. In 102 (97%) patients the leukapheresis sessions were started as planned at day 8. The median number of collected HPC was 7.3 × 10 6 /kg BW (0.2-18.3) with original filgrastim compared to 9 × 10 6 /kg BW (4.2-23.8) with the biosimilar filgrastim (P = 0.16). HPC collection was successful in 57 (93%) of 61 patients of the original group and in all 44 (100%) patients of the biosimilar group (P = 0.14). No differences were observed regarding side effects. Duration of neutrophil engraftment after autologous HPC transplantation was similar between the two groups (P = 0.17). Biosimilar and original filgrastim achieve comparable results in combination with vinorelbine regarding HPC mobilization and transplantation outcome in multiple myeloma patients. J. Clin. Apheresis 32:21-26, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

We aimed to assess the efficacy of vinorelbine plus granulocyte colony-stimulating factor (G-CSF) for chemo-mobilization of CD34(+) hematopoietic progenitor cells (HPC) in patients with multiple myeloma and to identify adverse risk factors for successful mobilization. Vinorelbine 35 mg/m(2) was administered intravenously on day 1 in an outpatient setting. Filgrastim 5 μg/kg body weight (BW) was given twice daily subcutaneously from day 4 until the end of the collection procedure. Leukapheresis was scheduled to start on day 8 and be performed for a maximum of 3 consecutive days until at least 4 × 10(6) CD34(+) cells per kg BW were collected. Overall, 223 patients were mobilized and 221 (99%) patients proceeded to leukapheresis. Three (1.5%) patients required an unscheduled hospitalization after chemo-mobilization because of neutropenic fever and renal failure (n = 1), severe bone pain (n = 1), and abdominal pain with constipation (n = 1). In 211 (95%) patients, the leukaphereses were started as planned at day 8, whereas in 8 (3%) patients the procedure was postponed to day 9 and in 2 (1%) patients to day 10. In the great majority of patients (77%), the predefined amount of HPC could be collected with 1 leukapheresis. Forty-four (20%) patients needed a second leukapheresis, whereas only 6 (3%) patients required a third leukapheresis procedure. The median number of CD34(+) cells collected was 6.56 × 10(6) (range, .18 to 25.9 × 10(6)) per kg BW at the first day of leukapheresis and 7.65 × 10(6) (range, .18 to 25.9 × 10(6)) per kg BW in total. HPC collection was successful in 212 (95%) patients after a maximum of 3 leukaphereses. Patient age (P = .02) and prior exposition to lenalidomide (P < .001) were independent risk factors for a lower HPC amount collected in multiple regression analysis. Vinorelbine plus G-CSF enables a very reliable prediction of the timing of leukapheresis and results in successful HPC collection in 95% of the patients., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Tumors can be targeted by the adoptive transfer of chimeric antigen receptor (CAR) redirected T-cells. Antigen-specific expansion protocols are needed to generate large quantities of redirected T-cells. We aimed to establish a protocol to expand functional active NY-ESO-1-specific redirected human CD8(+) T-cells., Materials and Methods: The anti-idiotypic Fab antibody A4 with specificity for HLA-A 0201/NY-ESO-1157-165 was tested by competition assays using a HLA-A 0201/NY-ESO-1157-165 tetramer. HLA-A 0201/NY-ESO-1157-165 redirected T-cells were generated, expanded and tested for CAR expression, cytokine release, in vitro cytolysis and protection against xenografted HLA-A 0201/NY-ESO-1157-165-positive multiple myeloma cells., Results: A4 demonstrated antigen-specific binding to HLA-A 0201/NY-ESO-1157-165 redirected T-cells. Expansion with A4 resulted in 98% of HLA-A 0201/NY-ESO-1157-165 redirected T-cells. A4 induced strong proliferation, resulting in a 300-fold increase of redirected T-cells. After expansion protocols, redirected T-cells secreted Interleukin-2, (IL-2), interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) and lysed target cells in vitro and were protective in vivo., Conclusion: A4 expanded HLA-A 0201/NY-ESO-1157-165 redirected T-cells with preservation of antigen-specific function.

Principles: High-dose chemotherapy with subsequent autologous stem cell transplantation (ASCT) is an important treatment option in younger patients with multiple myeloma (MM). We analysed the outcome of patients treated at our institution outside the clinical trials framework and tried to identify risk factors prognostic for survival., Methods: Medical histories of the patients were screened for response, event-free survival (EFS) and overall survival (OS). Pre-transplant variables were analysed to identify possible prognostic risk factors., Results: Overall, 182 ASCT were performed in 120 patients with MM from 2002 to 2007. Treatment-related mortality (TRM) was 0.5%. Median EFS was 23.1 months (95% confidence interval [CI]: 19.4-28.4) and median OS was 49.8 months (95%CI: 43.7 - not reached) in the whole patient population. The median OS in patients who received one ASCT was 46.4 months (95%CI: 35.2 - not reached), and 63.7 months (95%CI: 48.9 - not reached) in patients who underwent double ASCT. Patients who already achieved a complete remission (CR) before ASCT had a longer EFS (p = 0.016) than patients without CR. Additionally, patients who achieved a CR after ASCT had a longer EFS (p = 0.0061) and OS (p = 0.0024) than patients without CR. ISS stage

To reduce the duration of neutropenia after conditioning chemotherapy and autologous peripheral blood stem cell transplantation (APBSCT), granulocyte-colony stimulating factors (G-CSF) are commonly administered. We retrospectively evaluated the impact of pegfilgrastim compared to filgrastim on neutrophil engraftment, hospital stay, and supportive measures in patients with multiple myeloma after conditioning with Melphalan 200 (Mel200) followed by APBSCT. Ninety-two APBSCT after Mel200 treatment were performed in 72 patients between January 2006 and December 2009 at our institution. Patients received either single-dose pegfilgrastim (n = 46; 50%), or daily filgrastim (n = 46; 50%) after APBSCT (median duration of filgrastim use, 9 days; range, 3-14 days). Duration of neutropenia grade IV was shorter with pegfilgrastim compared with filgrastim (median, 5 days (range, 3-14 days) versus 6 days (range, 3-9 days), p = 0.0079). The length of hospitalization differed significantly (pegfilgrastim (median, 14.5 days; range, 11-47 days) versus filgrastim (median, 15.5 days; range, 12-64 days), p = 0.024). Pegfilgrastim-treated patients had less red blood cell transfusions (median, 0 transfusions (range, 0-10) versus 0.5 transfusions (range, 0-9), p = 0.00065). Pegfilgrastim was associated with reduced cost of the treatment procedure compared with filgrastim (p = 0.031). Pegfilgrastim appears to be at least equivalent to filgrastim without additional expenditure in myeloma patients treated with Mel200 and APBSCT.