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.