Incidence of Neutropenic Fever at a Safety Net Hospital in Cancer Chemotherapy Patients Receiving Prophylactic Pegfilgrastim Manual Injection Compared to the on-Body Auto-Injector

Introduction

Febrile neutropenia (FN) is a potentially life-threatening complication of chemotherapy, with increased incidence in pts receiving high risk chemotherapy regimens and/or over age 65¹. Prophylactic filgrastim given daily or once dosing/cycle pegfilgrastim have been shown to decrease the incidence, duration, and severity of neutropenia, fever and infection in patients receiving high risk cancer chemotherapy. Pegfilgrastim stimulates the production, maturation, and activation of neutrophils. Because of its stimulatory effects on neutrophil precursors, it should be given 24 hours after chemotherapy to reduce paradoxical neutropenia. For many pts, particularly those who are underinsured and who will not have home injection covered, this requires a return visit to the clinic. In 2015, a new device delivery of this medication was introduced called the Neulasta® On-Body Injector (OBI) Onpro®.This is a small, lightweight, waterproof device that is timed to deliver an injection 27 hours after application, resulting in less clinic visits. The on-body injector has been shown to be safe in healthy volunteers² and have pharmacokinetics similar to manual pegfilgrastim³. However, there is limited clinical efficacy data comparing the 2 delivery systems, particularly in an indigent care setting where adherence to home delivery systems may be an issue.

Methods

Between May 1, 2016 and May 30, 2017 the use of pegfilgastrim delivery systems as prophylaxis was reviewed at a large, urban cancer center. There were 120 patients identified: 60 returned the next day for manual injection of pegfilgrastim and 60 were ordered the home on-body injector. Primary data collected included the incidence of neutropenic fever, absolute neutrophil count (ANC) on admission, length of hospital stay, and on-body device failures.

Results

All pts received high risk chemotherapy regimens. Within each group (injection and OBI, respectively): ave age was 55.6 vs 56.1 (p = 0.78); sex 65% vs 92% female (p = 0.02); race 60% vs 68% White, 27% vs 22% African American, 3.3% vs 6.7% Hispanic, 5% vs 3.7% Asian (p = 0.7); cancer type: 38.3% vs 11.7% (p < 0.001) NHLymphoma, 28.3% vs 55% breast (p = 0.003), 8.3% vs 6.7% lung (p = 0.73), 25% vs 26.7% other cancer (p = 0.83); 21.7% vs 33.3% had commercial insurance, 73.3% vs 56.7% had Medicare/Medicaid, 5% vs 10% had self-pay.

Overall, 17/120 (14%) patients developed FN: 10/60 (16.7%) from the manual injection group vs 5/60 (8.3%) from the OBI group (p = 0.17). 100% of FN patients were admitted for inpatient care and were treated with intravenous antibiotics in both groups. Of those that developed FN, nadir ANC on average was 160 vs 432 (p = 0.22), length of stay 6.6 vs 4.4 days (p = 0.497), 67% vs 40% had advanced cancer (p = 0.003), 70% vs 0% of patients that developed FN had lymphoma; 16.7% vs 20% were >65 years of age (p = 0.64), 8.3% vs 20% had ECOG ≥2 (p = 0.067), and 25% vs 20% had evidence of kidney or liver dysfunction (p = 0.51).

Three patients (5%) reported the on-body injector falling off after attachment. One patient did not pick up the on-body injector. These four patients received a manual injection in clinic the following day. None of these patients had FN within 30 days post chemotherapy.

Conclusion

Cancer pts at a safety net institution receiving post-chemotherapy prophylactic pegfilgrastim were not found retrospectively to have had an increased incidence of febrile neutropenia when using the OBI compared to the manual subcutaneous injection. There was a non-significant increase in FN in the manual injection group but this may have been due to a significant imbalance of more myelosuppressive NHL regimens. Overall, in pts exposed to high risk chemotherapy, OBI use resulted in a low incidence of FN (8.3%) and fewer return clinic visits but education on handling device failure is vital to the effectiveness of the pegfilgrastim OBI in this patient population.

¹Myeloid Growth Factors. National Comprehensive Cancer Guidelines (NCCN), Version 1.2018. http://www.nccn.org/.

²Josh RS et al. Performance of the pegfilgrastim on-body as studied with placebo buffer in healthy volunteers. Curr Med Res Opin. 2017; 33(2): 379-384.

³Yang BB et al. Comparison of pharmacokinetics and safety of pegfigrastim administered by 2 delivery methods: on-body injector and manual injection in a prefilled syringe. Can Chemo Pharmacol. 2015; 75(6): 1199-1206.