A Randomized Trial of Tbo-Filgrastim Versus Filgrastim for Autologous Stem Cell Mobilization in Patients with Multiple Myeloma or Non-Hodgkin Lymphoma

Background: Tbo-filgrastim, biosimilar to filgrastim, was approved by the FDA in 2012 as a new drug due to the lack of a biosimilar approval pathway at time of submission. Like filgrastim, tbo-filgrastim is currently indicated for the treatment of neutropenia following chemotherapy; however, filgrastim is also indicated for mobilization of hematopoietic progenitor cells for autologous stem cell transplantation (ASCT) while tbo-filgrastim is not. In Europe, tbo-filgrastim carries all the indications that filgrastim does, however, no prospective studies have been completed comparing tbo-filgrastim and filgrastim for ASCT mobilization. Therefore, we conducted a single-institution randomized phase 2 trial.

Objectives: 1) To compare peripheral blood (PB) CD34⁺ counts, CD34⁺ apheresis yield, toxicity, and post-ASCT engraftment in patients mobilized with tbo-filgrastim versus filgrastim.

Methods: Participants were at least 18-years-old and had multiple myeloma (MM) or non-Hodgkin’s Lymphoma (NHL). Those with impaired hematologic function and those who had undergone a previous ASCT mobilization were excluded. Participants were randomized (1:1) to tbo-filgrastim or filgrastim. Tbo-filgrastim/filgrastim (10mcg/kg) was administered daily for 5 days. On the evening of Day 4, plerixafor (0.24 mg/kg) was administered; apheresis (20L) was performed on Day 5. If a participant failed to achieve the target collection goal (5.0x10⁶ cells/kg) on Day 5, he/she continued to receive daily tbo-filgrastim/filgrastim, plerixafor, and apheresis for a maximum of 3 additional days. Participants who subsequently underwent ASCT were followed for platelet and neutrophil engraftment.

Statistics: PB CD34⁺ counts and CD34⁺ apheresis yields were compared using Mann-Whitney U, engraftment using log-rank.

Results: At the time of abstract submission, corresponding with interim analysis 1, 51 participants were enrolled and 49 were evaluable for analysis; 24 received tbo-filgrastim, 25 filgrastim. The median age was 60 years (range 40-77); 63% (31) were male; 86% (42) had MM, 14% (7) NHL. Both treatment arms were similar in demographics and baseline blood counts.

Post-mobilization PB CD34⁺ counts were similar between both arms. The median PB CD34⁺ count on day 4 (pre-plerixafor) was 20/mcL for tbo-filgrastim and 22/mcL for filgrastim (p=0.647); on Day 5 pre-apheresis it was for 94/mcL for tbo-filgrastim and 92/mcL for filgrastim (p=0.726). CD34⁺ apheresis yield was also similar; the median Day 5 CD34⁺/kg apheresis yield was 10.9x10⁶ for tbo-filgrastim and 12.0x10⁶ for filgrastim (p=0.889).

Seventy-five percent of the tbo-filgrastim arm reached the collection goal after one day of apheresis, 76% of the filgrastim arm did (p=0.935). Ninety-six percent of patients on the tbo-filgrastim arm reached the goal in 4 or less days of apheresis, 92% of the filgrastim arm did (p=0.576). All patients treated collected > 2.0x10⁶ cells/kg, the minimum required for ASCT, following < 2 days of apheresis. Both treatment arms had similar toxicity.

Thirty-nine patients have subsequently undergone ASCT and evaluable for engraftment, 18 on the tbo-filgrastim arm and 21 on the filgrastim arm. The median interval of neutrophil engraftment for tbo-filgrastim was 12 days compared to 11 for filgrastim (p=0.178); the median interval of platelet engraftment was 17 days for both arms (p=0.238).

Mobilization, collection, toxicity, and engraftment data are summarized in Table 1.

Conclusion: Tbo-filgrastim appears to be similar to filgrastim for ASCT mobilization in patients with MM or NHL. Planned study enrollment is 100 evaluable patients; updated study results will be presented.

Table 1

	Tbo-Filgrastim	Filgrastim
PB CD34+/mcl on Day 41 (median & range)	20 (4-68)	22 (1-115)
PB CD34+/mcl on Day 5 (median & range)	94 (18-187)	92 (11-314)
CD34+/kg x106 yield on Day 5 (median & range)	10.9 (1.4-21.2)	12.0 (1.3-28.4)
CD34+/kg yield >2.0 on Day 5	96%	92%
CD34+/kg yield >5.0 on Day 5	75%	76%
CD34+/kg yield >2.0 in < 4 days	100%	100%
CD34+/kg Yield >5.0 in < 4 days	96%	92%
Post-ASCT Engraftment
Days to Neutrophil Engraftment (median & range)	12 (10-20)	11 (10-13)
Days to Platelet Engraftment (median & range)	17 (13-23)	17 (13-22)

1-      Prior to plerixafor dose