Pegfilgrastim (6mg or 12mg) Mobilizes CD34+ Cells Similarly to Filgrastim (5mcg/kg/day) When Administered Following Chemotherapy in Patients with Non-Hodgkin’s Lymphoma.

Abstract

Introduction: This phase 2, randomized, double-blind, dose-finding study assessed peripheral blood progenitor cell (PBPC) yields using 2 pegfilgrastim doses plus chemotherapy (CT) in patients (pts) with non-Hodgkin’s lymphoma considered suitable for high-dose CT and autologous PBPC transplant. Methods: Pts were given standard mobilizing CT (ICE: etoposide 100mg/m2 days 1, 2, 3; carboplatin AUC 5 day 2; ifosfamide 5 g/m2 day 2) followed by single-dose pegfilgrastim (6 or 12mg) or daily filgrastim (5 mcg/kg). Leukapheresis began when the peripheral CD34+ count was ≥10/mcL and white blood cell count was ≥2.5x109/L and continued until a CD34+ yield of ≥5x106/kg was obtained or a maximum of 5 aphereses were performed. Daily filgrastim was discontinued after the last apheresis. Pts with sufficient PBPC yields (≥2x106/kg) then received high-dose CT (BEAM: BCNU 300mg/m2, etoposide 800mg/m2, cytarabine 1600mg/m2, melphalan 140mg/m2) followed by PBPC transplantation and subsequent filgrastim until absolute neutrophil counts (ANC) recovered. Successful engraftment post-transplant was defined as 2 consecutive ANCs >0.5x109/L and platelet counts of >20x109/L independent of transfusions. Pts who did not have a collection were assigned a CD34+ yield of 0. Non-parametric descriptive statistics and Kaplan-Meier survival analyses were generated. Results: A total of 92 pts were randomized, and 90 received study medication (29 pegfilgrastim 6mg or 12mg, 32 filgrastim). Baseline demographics and medical characteristics were balanced across groups. A similar number of pts per group had at least one leukapheresis (21 pegfilgrastim 6mg; 20 pegfilgrastim 12mg; 25 filgrastim). The median (range) for mean harvest per leukapheresis was 1.18x106 CD34+ cells/kg (0.0 to 11.4) for pegfilgrastim 6mg, 1.44 x106 (0.00 to 9.45) for pegfilgrastim 12mg,and 1.59x106 (0.00, 10.37) for filgrastim. Twenty (69%) pegfilgrastim 6mg, 17 (59%) pegfilgrastim 12mg, and 23 (72%) filgrastim pts had a harvest of ≥2x106 CD34+ cells/kg. Seventeen (85%) pegfilgrastim 6mg, 16 (94%) pegfilgrastim 12mg, and 18 (78%) filgrastim pts who achieved a yield of ≥2x106 CD34+ cells/kg reached this target yield in 1–2 leukaphereses. Median (range) number of days of filgrastim use in the collection phase was 12 (8 to 25). All pts who received a transplant on-study successfully engrafted except for 1 pt (pegfilgrastim 6mg) who died 4 days post-transplant. Median (95% CI) time to ANC recovery of at least 0.5x109/L was 12 (10,13), 11 (10,13), and 11 (10,12) days for the pegfilgrastim 6mg, pegfilgrastim 12 mg, and filgrastim groups, respectively. Time to platelet recovery of at least 20x109/L was 11 days for all groups. Safety profiles were similar for each group, and both treatments were well tolerated. Conclusions: This study suggests pegfilgrastim is similar to filgrastim in the setting of CT mobilization. Pegfilgrastim 6mg appears as effective as pegfilgrastim 12mg with respect to PBPC mobilization, collection, and engraftment. Further study with pegfilgrastim 6mg compared with filgrastim 5mcg/kg in this setting is warranted.

Efficacy of single‐dose pegfilgrastim after chemotherapy for the mobilization of autologous peripheral blood stem cells in patients with malignant lymphoma or multiple myeloma

“…An association between ANC count at pegfilgrastim administration and mobilization efficacy, however, could not be demonstrated in our series. Similar harvest results after chemotherapy and single doses of 6 and 12 mg of pegfilgrastim as well as after daily administrations of 5 µg per kg filgrastim were also reported in a Phase II randomized, double‐blind trial including 90 lymphoma patients that was reported most recently 25 …”

“…Similar harvest results after chemotherapy and single doses of 6 and 12 mg of pegfilgrastim as well as after daily administrations of 5 µg per kg filgrastim were also reported in a Phase II randomized, double-blind trial including 90 lymphoma patients that was reported most recently. 25 The interpretation of this study is limited by the small number of patients and the heterogeneity of the population in terms of underlying disease and mobilization chemotherapy. Nevertheless, the results are consistent and compatible with the experiences from PBPC mobilization…”

Fixed‐dose single agent pegfilgrastim for peripheral blood progenitor cell mobilisation in patients with multiple myeloma

“…Preliminary data from animal studies and normal human volunteers also suggests that pegfilgrastim may be able to mobilise peripheral blood progenitor cells with a single subcutaneous injection without added toxicity, and thus, avoid the need for repeated injections (Molineux et al , 1999; Johnston et al , 2000; Russell et al , 2005; Bruns et al , 2006). We present the results of a phase II study of pegfilgrastim administered as a single subcutaneous injection to mobilise progenitor cells into the peripheral blood of patients with multiple myeloma who were scheduled to receive high‐dose chemotherapy and autologous peripheral blood progenitor cell transplantation (APBPCT).…”