Comparison of Early Versus Delayed Filgrastim (G-CSF) Administration Following Autologous Stem Cell Transplantation in Patients with Multiple Myeloma - Real-World Data from a Single-Center Institution
Authors: Monge Jorge , Flicker Kari , Guarneri Danielle , Solomon Robin S. , Guo Jin , Contreras Jorge , Agudo Natalie , Jayabalan David S , Pogonowski Kathleen , Liotta Brielle , Hsu Jingmei , Phillips Adrienne A. , Mayer Sebastian A. , Gergis Usama , Shore Tsiporah B. , Van Besien Koen , Coleman Morton , Rosenbaum Cara A. , Pearse Roger , Rossi Adriana C. , Niesvizky Ruben 
Published: November 2019

Background:
Autologous stem cell transplantation (ASCT) performed early in the disease course or at first relapse leads to improved progression-free and overall survival in transplant-eligible patients with multiple myeloma (MM). Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF), when used after ASCT has been shown to accelerate time to neutrophil engraftment (TNE), and in some studies, it has been associated with reduced length of hospitalization, infectious complications, and antibiotic use. Strategies that reserve G-CSF administration to when neutrophil recovery is delayed, have attempted to show that there is no difference in infectious complications, length of hospitalization or TNE when compared to early administration of G-CSF on the day after stem cell infusion (DOT). However, the optimal timing for administering G-CSF has not yet been determined in patients with MM undergoing ASCT.
Methods:
This is a retrospective, single-center analysis of patients with MM undergoing ASCT from mobilized peripheral blood stem cells. Patients enrolled in a clinical trial of high-dose lenalidomide and melphalan as conditioning therapy which mandated the administration of filgrastim from day +1 after DOT (Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma, NCT01054196) were assigned to the early strategy group (ES). Patients receiving filgrastim as per our institutional guideline (starting on day +12 if ANC < 1000 cells/uL, or at the physician's discretion) were included in the delayed strategy group (DS). Patients were excluded from the analysis if their conditioning regimen included a different agent other than melphalan or lenalidomide. DOT was defined as the day of stem cell infusion. Date of neutrophil engraftment was defined as the first of three consecutive days with an ANC ≥ 500 cells/uL. TNE was calculated as the time from DOT to the date neutrophil engraftment. Total duration of neutropenia was defined as the time from onset of neutropenia (ANC < 500 cells/uL) to date of neutrophil engraftment. Length of hospitalization was defined as the time from DOT to the day of discharge.
Results:
We identified 59 patients in the ES group and 39 patients in the DS group from 08-16-2010 to 05-22-2019, for a total of 98 included in this analysis. Median age was 60 and 65 years in the ES and DS groups, respectively. Patients received a comparable dose of CD34+ cells, 5.05x106/kg in the ES group vs 4.66x106/kg in the DS group (p = 0.48). The ES group started filgrastim administration earlier (day +1 vs +9, p < 0.001) and received a greater median number of doses (10 vs 4, p < 0.001) as compared to patients in the DS group. Median time to neutrophil engraftment was shorter in the ES group compared to the DS group (10 vs 12 days, p < 0.001), as was the total duration of neutropenia (5 vs 6 days, p < 0.001). Documented infections were just as likely in both groups, 37% in the ES group and 39% in the DS group (p = 1). Length of hospitalization was shorter in the ES group as compared to the DS group (15 vs 17 days, p = 0.01).
Discussion:
Filgrastim use guided by an ES decreased the time to neutrophil engraftment, the duration of neutropenia and the length of hospitalization compared to a DS. Further analyses to identify predictive factors associated with a reduction in infectious complications and length of stay are underway, with the aim of developing a risk-adapted strategy for the use of filgrastim in patients with MM undergoing ASCT.

Disclosures
Van Besien: Miltenyi Biotec: Research Funding. Coleman:Kite Pharmaceuticals: Equity Ownership; Merck: Research Funding; Pharmacyclics: Speakers Bureau; Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau. Rosenbaum:Janssen: Research Funding; Honoraria Akcea: Other: Accordant Health. Rossi:Janssen, Celgene, Amgen: Consultancy; BMS: Research Funding. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding.