Combined Use of Palifermin and Pegfilgrastim Significantly Reduces Toxicity of High-Dose Therapy and Autologous Blood Stem Cell Transplantation in Patients with Multiple Myeloma.

Abstract

Background: The use of conventional G-CSF after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) has resulted in earlier hematopoietic reconstitution in comparison to patients not receiving hematopoietic growth factors. We have shown that a single injection of 6mg Pegfilgrastim after ASCT results in sustained high G-CSF serum levels and fast hematopoietic reconstitution in patients with multiple myeloma (Fenk et al, Exp Hematol, in press). However, duration of hospitalisation and need for supportive care were only marginally improved by Pegfilgrastim. We therefore added a short-course of Palifermin, a recombinant human keratinocyte growth factor, before HDT to further reduce toxicity.Patients and Methods: So far 15 patients (the Pal-Peg-group, 8 male, 7 female, median age 59, range 45–73) with multiple myeloma received 3 daily injections of Palifermin (60ug/kg/d) before HDT. At least 24 hours after the last Palifermin dose patients were treated with high-dose melphalan (median dose 200mg/m2, range 100–200) followed by ASCT of a median of 3.5×10E6CD34+cells/kg (range 1.9–18.8). Pegfilgrastim (6mg) was given one day after blood stem cell infusion. This group of patients was compared to a previous cohort of 21 patients (the Peg-only-group, 9 male, 12 female, median age 57, range 39–69) with multiple myeloma who had received a median of 4.5×10E6CD34+cells/kg (range 2–12) and 6mg Pegfilgrastim after HD-melphalan conditioning but without Palifermin pretreatment. Patients in the Pal-Peg-group had more advanced disease.Results: Time to hematopoietic reconstitution was not significantly different in both groups with a median time to a WBC >1×10E9/l of 11 days (range 9–13) in the Pal-Peg-group and 10 days (median, range 9–14) in the Peg-only-group (p=ns). The same was true for platelet reconstitution. Due to a markedly reduced incidence and severity of mucositis in the Pal-Peg-group the duration of hospitalisation was significantly shorter (median 17 days, range 13–23 vs 21 days, range 15–34, p<0.05). In addition the need for iv antibiotics (median 0 days, range 0–9 vs 4 days, range 0–21), morphine (median 0 days, range 0–12 vs 4 days, range 0–21) and erythrocyte transfusions (median 0, range 0–4 vs 2, range 0–14) was significantly reduced (p<0.05 for all). Because some patients needed parenteral nutrition (PEN) for prolonged nausea the reduction in PEN was not significant so far (median 0 days, range 0–12 vs 6 days, 0–16, p=0.07)Conclusion: The combined use of a short course of Palifermin and Pegfilgrastim significantly reduces toxicity after HDT and ASCT in patients with multiple myeloma and improves patient convenience. As some patients still had severe mucositis further research should focus on predictive factors to identify patients who may benefit from an extended use of Palifermin before and after HDT.