Low-Dose Filgrastim Provides Cost Savings and Noninferior Clinical Outcomes for Some Patients

The recommended dose of filgrastim is 5 ug/kg, but due to limitations in dosage formulations (commercially available vials are provided in doses of 300 ug and 480 ug), patients who weigh more than 60 kg—for whom an ideal dose would be above 300 ug but under 480 ug—often receive a subtherapeutic dose of filgrastim. In other cases, patients for whom an optimal dose is between 300 ug and 480 ug may be billed for the cost of a full 480 ug vial of filgrastim, even if they did not require the entirety of the higher-dose vial.

To determine whether a course of 300 ug of filgrastim, administered daily for 2 days, achieves the same clinical outcomes that have been reported with the recommended dosage, and whether such a dose could provide cost savings, investigators from Marshall University performed a retrospective chart review to identify all patients at their institution with chemotherapy-induced neutropenia who were treated with 2 consecutive doses of 300 ug of filgrastim between September 2011 and September 2016.

The researchers identified 91 patients (and 150 encounters) who were divided into categories of low weight (<60 kg), medium weight (<85 kg), and high weight (≥85 kg). Patients at low weight received the recommended 5 ug/kg dose and were therefore treated as the control group. Patients in the medium- and high-weight groups were receiving subtherapeutic doses of filgrastim based on the label recommendations.

In total, 30 patients were classified as low weight, 53 as medium weight, and 8 as high weight. The mean total doses in ug/kg administered over the course of 2 days were 7.37 (SD = 2.28), 8.38 (SD = 3.11), and 11.19 (SD = 4.58) for the 3 groups, respectively.

The average time elapsed between filgrastim treatment and a repeat complete blood count was 6.63 days (range, 1-22). Following filgrastim treatment, 98% and 95.33% of encounters had documented rises in white blood cell count (WBC) and absolute neutrophil count (ANC), respectively:

• Low weight: 95.74% of encounters had rises in WBC and 95.74% had rises in ANC
• Medium weight: 98.9% had rises in WBC and 94.51% had rises in ANC
• High weight: 100% had rises in WBC and 100% had rises in ANC.

Patients in the high-weight group had a statistically significantly higher rate (33%) of infection 2 weeks following filgrastim administration than the low-weight (0%) and medium-weight (5.49%) groups (P = .001).

The researchers concluded that, for patients of medium weight, lower-dose filgrastim resulted in similar WBC and ANC responses compared with patients who received the recommended dose of filgrastim (low-weight patients). However, higher infection rates among the high-weight group suggests that those weighing 85 kg or more may have inferior outcomes with low-dose filgrastim.

Furthermore, the researchers write that, in the 91 encounters for the medium-weight cohort, assuming a wholesale cost of $1889.20 for a 480-ug vial versus $1080 for a 300-ug vial of filgrastim (a 43% cost difference per dose), using low-dose filgrastim provided a savings of $147,274.40.

“Given the small size of this cohort, these cost savings would no doubt have significant implications at a national level if non-inferiority is able to be further corroborated,” write the authors. “Also, it is important to note that this analysis only takes into account potential savings from the lower dosage utilized but not from a [2]-day versus the typical multiple-day dosing.”

Reference

Singh R, Heisey H, Elsayed AG, Tirona MT. Adequate neutrophil responses and non-inferior clinical outcomes can be achieved by a two-day course of low-dose filgrastim: a retrospective single institution experience. Cureus. 2017;9(12):e1968. doi: 10.7759/cureus.1968.